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Transforming Psychedelics into Mainstream Medicines | +50 articles

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Ancient records and oral traditions detail the use of peyote cacti for treating inflammation, promoting wound healing, and easing pain.

Transforming psychedelics into mainstream medicines

by Shlomi Raz | STAT | 7 Jan 2020

Research on psychedelics, which have been profoundly stigmatized, highly restricted, and tragically undeveloped for more than half a century, is stirring back to life and rekindling scientific, medical, and cultural interest in these compounds.

I’m not talking about microdosing psilocybin or other psychedelics for their anecdotal effects on productivity, focus, or creativity. What I’m referring to is a serendipitous discovery arising from this renaissance of research showing that psychedelics could someday be transformed into anti-inflammatory and antidepressant medicines devoid, at clinically relevant dose levels, of their distinctive effects on perception, cognition, mood, and more.

Humans have used psychoactive plants as medicines since the dawn of civilization. Ancient records and oral traditions detail the use of peyote cacti and cannabis plants for treating inflammation, promoting wound healing, and easing pain.

Eighty years ago, the renowned Harvard ethnobotanist Richard Evans Schultes wrote that the use of low-dose peyote was “centered around the therapeutic and stimulating properties of the plant and not around its vision-producing properties…Some of the ills listed as responding to peyote were tuberculosis, pneumonia, scarlet fever, intestinal ills, diabetes, rheumatic pains, colds, grippe, fevers, and venereal diseases…It is used as a white man uses aspirin.”

At the high doses that profoundly alter perception, psychedelics serve as religious sacraments. Psilocybin and lysergic acid diethylamide, better known as LSD, are now being evaluated in Phase 2 clinical trials for the treatment of depression. Research conducted at Johns Hopkins University has confirmed the robust spiritual significance of psychedelic experiences at high doses of psilocybin, while researchers have shown in clinical trials that high-dose psychedelics such as psilocybin, LSD, and ayahuasca exert rapid, significant, and enduring antidepressive effects.

These high-profile research findings have obscured the primary traditional use of these medicines — as imperceptible anti-inflammatory agents.

In 2008, a psychedelic compound related to the primary psychoactive alkaloid in peyote was discovered to exert “extraordinarily potent” anti-inflammatory effects at very low drug concentrations in vitro and in vivo. Additional studies have confirmed the capacity of psychedelics to modulate processes that perpetuate chronic low-grade inflammation and thus exert significant therapeutic effects in a diverse array of preclinical disease models, including asthma, atherosclerosis, inflammatory bowel disease, and retinal disease.

Of note, some psychedelics can act as anti-inflammatory agents at concentrations unlikely to induce changes in brain function that alter perception, mood, thinking ability, or behavior. This suggests they are capable of being transformed into so-called subperceptual medicines.

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Shlomi Raz

Eleusis, the company I founded in 2014, is focused on unlocking the therapeutic potential of serotonin 2A receptor agonists, commonly referred to as psychedelics, by reducing or managing their perceptual effects. The primary neuroreceptor that mediates psychedelics’ psychoactivity, the serotonin 2A receptor, is also known to play a key role in regulating immune function. Our research has revealed that some psychedelics that activate the serotonin 2A receptor are potently anti-inflammatory at doses unlikely to result in psychoactivity.

Chronic low-grade inflammation is at the root of aging and age-related disease. Termed “inflammaging,” this insidious dysregulation of the immune system contributes to the disease burden in older adults and accelerates the aging process. In fact, healthy centenarians are distinguished primarily by low levels of chronic inflammation.

Alzheimer’s disease is an exemplar of inflammaging. It is distinguished by a complex and multifactorial pathobiology that appears resistant to single-target “precision medicines,” each of which is designed to modulate just one of the many dysregulated processes giving rise to neurodegeneration. To adequately address the multifactorial nature of Alzheimer’s disease, researchers have advocated for the development of new drugs that simultaneously engage multiple therapeutic targets, an approach typically avoided in drug development due to its complexity and high cost.

According to a Chinese proverb attributed to Confucius, “Better a diamond with a flaw than a pebble without.” To the discerning pharmacologist, LSD is a diamond without equal — a notoriously psychoactive drug with muted physiological effects that is capable of potent and prolonged activation of serotonin and dopamine neurotransmission receptors. The unique pharmacology of LSD enhances its capacity to simultaneously modulate multiple therapeutic targets in the brain associated with inflammaging that are implicated in the progression of mild cognitive impairment to Alzheimer’s, including amyloid precursor protein processing, cognition and memory function, neuroplasticity, neuroinflammatory processes, neuronal viral infection, insulin resistance, oxidative stress, neuroendocrine function, metabolic function, and epigenetic expression.

We have also recently published results of a Phase 1 clinical trial showing the safety and tolerability of low-dose LSD among older volunteers, who generally couldn’t distinguish the low doses from placebo. This trial was a prelude to a definitive long-term evaluation of LSD in patients at risk of developing Alzheimer’s disease.

Eleusis isn’t alone in evaluating the potential of psychedelics for treating diseases of the body and the brain.

The U.S. Defense Advanced Research Projects Agency recently acknowledged the potential of subperceptual psychedelics. To address the high rate of mental illness among active duty military personnel, DARPA aims to discover new compounds that can exert the rapid and robust antidepressant effects of psychedelics without the associated “trip.”

In the private sector, Compass Pathways is conducting Phase 2 trials of psilocybin for treatment-resistant depression, while the Usona Institute, a not-for-profit medical research organization, is similarly engaged in Phase 2 trials of psilocybin for major depression. Scores of research groups and companies have published studies of the potential of using psychedelics for medicines in just the past few years.

The FDA’s groundbreaking approval of GW Pharmaceuticals’ Epidiolex, a medicine made from cannabis, to treat two rare and severe forms of epilepsy, has paved the way for making psychedelics into medicines. The clinical development of cannabidiol (CBD) into an FDA-approved therapy is an inspiring example of how traditional medicines can be transformed into modern ones through advanced pharmacological techniques that ensure patient safety.

The time has come to make psychedelics, once seen as “out there” substances, mainstream and boring again.

Interview with Shlomi Raz, CEO and Chairman of Eleusis Ltd, based in London

 
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University of Las Vegas

Psychedelic Science holds promise for Mainstream Medicine

UNLV neuroscientists Dustin and Rochelle Hines join rising number of researchers studying possible medical benefits of psychedelics.

Psychedelic healing may sound like a fad from the Woodstock era, but it’s a field of study that’s gaining traction in the medical community as an effective treatment option for a growing number of mental health conditions.

While the study of psychedelics as medicine is inching toward the mainstream, it still remains somewhat controversial. Psychedelics have struggled to shake a “counterculture” perception that was born in the 1960s, a view that had stymied scientific study of them for more than 50 years.

But that perception is slowly changing.

Mounting research suggests that controlled treatment with psychedelics like psilocybin mushrooms, LSD, and MDMA – better known as ecstasy – may be effective options for people suffering from PTSD, anxiety disorders, and depression. The U.S. Food & Drug Administration recently granted “breakthrough therapy” status to study the medical benefits of psychedelics. And two years ago this month, the FDA approved a psychedelic drug – esketamine – to treat depression.

An increasing number of states and municipalities are also grappling with calls to decriminalize psychedelic drugs, a move that UNLV neuroscientist Dustin Hines says could further the recent renaissance in psychedelic science.

“The resurgence in interest in psychedelic medicine is likely related to multiple factors, including decreasing societal stigma regarding drugs like hallucinogens and cannabis, increasing awareness of the potential therapeutic compounds found naturally occurring in plants and fungi, and the growing mental health crisis our nation faces,” says Hines. “Because of the intersection between the great need for innovation and wider social acceptance, researchers have started to explore psychedelics as novel treatments for depressive disorders, including work with compounds that have been used for millennia.”

In the Hines lab at UNLV, husband and wife researchers Dustin and Rochelle Hines are uncovering how psychedelics affect brain activity. Their work, published recently in Nature: Scientific Reports, shows a strong connection in rodent models between brain activity and behaviors resulting from psychedelic treatment, a step forward in the quest to better understand their potential therapeutic effects.

We caught up with the Hineses to learn more about the evolution of psychedelic science — which actually dates back thousands of years — their research (which doesn't date back as long), misconceptions about this emerging field of study, and what to expect next.

The scientific study of psychedelics holds great promise for people suffering with mental illness. Where do we stand?


Dustin Hines: It’s estimated that 1 in 5 American adults suffer from some type of mental illness. And while not all require pharmacological treatment, unfortunately there’s been limited progress in advancing novel therapies for depressive disorders in 50 or more years.

Rochelle Hines: It’s also worth noting that available therapies for major depression are only effective in specific segments of the depressed population. That’s what makes the study of psychedelic compounds so fascinating. Recent clinical studies have empirically demonstrated that these compounds can exert rapid antidepressant effects – essentially bringing into the clinic a practice that Mesoamerican and other cultures have used for thousands of years. But there are still quite a few regulatory barriers that limit even research use of psychedelics. We’re hopeful that as the public view of psychedelic compounds changes, so too will the federal regulations that currently govern their study.

Current therapies for mental health disorders can take weeks to become effective. Recent research, including your own, shows the potential for psychedelic compounds to work much more quickly. What do we know about how this happens?


Rochelle: Clinical research on the use of psychedelics as therapeutics suggests that they work by altering the connectivity, or communication, between brain regions. Multiple studies suggest that the connectivity of cortical sensory regions and other brain areas is strengthened. Studies have also reported alterations in the patterns of brain activity during psychedelic treatment in patients with depression.

Dustin: Our recent studies support the evidence for changes in patterns of brain activity, and provide additional detail into specific patterns of brain activity that are generated during psychedelic treatment. The brain activity patterns that we’ve characterized are related to specific behaviors known to occur following treatment with psychedelic hallucinogens. These findings support the idea that generation of specific brain activity patterns may be a key aspect of the beneficial effects that psychedelic compounds exert.

In your research, you discuss the long history of hallucinogens for ritualistic practices. What did these cultures know that we don’t, and how does your work draw upon this ancient evidence?


Rochelle: Modern medicine – which includes our research team – is reinvestigating psychedelic practices with a 5,000-plus year history. Mesoamerican practitioners are known to engage in specific processes that were honed over millennia of skilled use, often including the addition of nicotine to their ritualistic and therapeutic practices with psychedelics. At present, very little research has investigated the synergistic effects of psychedelics and nicotine.

Dustin: Despite this long history and recent clinical promise, we still really don’t know just how these drugs actually work on the brain to influence mood. This knowledge is essential to optimize their therapeutic potential. In our study of brain activity in a rodent model, we found that nicotine enhanced both the brain’s slow waveform as well as behavioral arrest, both hallmark aspects of the response to psychedelic hallucinogens. We’re now working on studies examining the synergy between psychedelics and nicotine, and whether nicotine enhances the anti-depressant effects of psychedelics.

Rochelle: We’re also investigating the cellular and molecular mechanisms that underlie the specific changes in brain activity following treatment with psychedelics. With this understanding, we may be able to further refine the clinical utility, applicability, and efficacy of psychedelic hallucinogens as medicines.

As researchers who study the possible therapeutic benefits of psychedelics, what are some of the biggest misconceptions you’ve encountered? How can further scientific study combat them?


Dustin: Microdosing of psychedelics — where users gain benefit, though not the prototypical “high” from small amounts the drugs is a practice that’s been in the news a lot lately. While there are some data suggesting that low doses can exert beneficial effects, the idea that a person can purchase controlled substances without clarity on the content of psychoactive ingredients and regulate their own dosing with precision is in my opinion misguided. By conducting research to examine both purified and synthetic compounds, we can more accurately establish dosing.

Rochelle: There’s a long-standing belief that these drugs are addictive. However, much of the research suggests that these drugs don’t result in maladaptive patterns of substance use behavior. To the contrary, some research actually suggests that these compounds may be effective in treating substance use disorders. More research on the effects of these compounds in models may provide better clarity on not only the acute effects, but the effects of repeated dosing.

Dustin: An important point to drive home with all of this is that psychedelics are powerful psychoactive drugs, and they should not be used for therapeutic purposes without an experienced practitioner.

The context surrounding the use of psychedelics as a therapy is emerging, but further research into the clinical use of psychedelics is needed to establish procedures and protocols that we hope will ultimately support positive outcomes for patients.

 
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The brave new world of psychedelics

by Katya Kowalski | Medium | 18 Jun 2020

These mind expanding drugs possess incredible potential for treating mental illness. What does the supporting evidence look like, and how do these drugs work?

Hallucinogenics have been a tool for gaining insight into the inner workings of the mind through spiritual ceremonies for centuries. However, the perceived threat to political order led to a ban on psychedelics in 1970 with no evidence-based justification. This shut the door to researching both the harms and benefits of these drugs. Although recently we have seen a renaissance of research into psychedelics and their remarkable treatment potential.

Let’s have a look at the evidence. A meta-analysis examined old clinical LSD trials for treating alcoholism. A single dose was associated with a decrease in alcohol misuse — LSD appeared to be as good as any other treatment for alcoholism developed since. Psilocybin trials have yielded similar results. The intensity of the psychedelic experience predicted changes in drinking and decreasing craving. Psilocybin has also provided astonishing results for tobacco addiction, 80% participants in the trial showed abstinence at 6-month follow up — a remarkable smoking cessation rate. Another follow-up study showed psilocybin holds considerable abilities for long-term smoking cessation

A recent trial found psilocybin to be effective for treatment-resistant depression, seeing profound long-lived improvements in mood and wellbeing remaining significant after 6-months. Comparably, LSD helps with coming to terms with death, reducing anxiety in individuals with terminal illness.

This is promising research.

Let’s look at how these drugs are effective. Psychedelics seem to change aspects of our personality by decreasing neuroticism and increasing extraversion, along with openness to experience. This explains their long-lasting effects. Mystical experiences during a psychedelic trip contribute to changes in behaviours, attitudes and values — a kind of rebirth if you like.

Let’s look deeper. Psychedelics change the way we think. The reason for this lay in the processes of the default mode network. What is this? The DMN makes our brain work in the way it always does, often referred to as the me network as it forms our ego and has a top-down influence on our brain.

The DMN is most active in our resting state when our minds wander, ruminate, reflect and worry — this consumes a large portion of our brains energy. However, too much self-reflection and rumination locks us into repetitive negative thoughts — a wandering mind is an unhappy mind.

Depression, addiction and anxiety are all disorders with an overactive DMN — becoming extremely ego focused, you are at the centre of your illness.

The solution? Psilocybin rewires our DMN. As you can imagine, your brain is in a very different state on psychedelics compared to your usual brain communication. Your brain is no longer obeying your commands, rather doing its own thing. You become liberated from your brains habitual processes, diluting those brain parts that are overactive in depression with negative thinking

Below is a figure developed from a brain imaging study. On the left is your brain on a placebo, normal communication. On right is your brain on psilocybin — your brain begins communicating between areas that do not normally communicate. This explains the novel, bizarre experience of tripping along with a change in thinking patterns.

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Our DMN is intertwined with our subjective experiences and ego. Psychedelics dissolve the DMN temporarily, leading to ego dissolution.

Your sense of self is temporarily gone. The boundaries we usually feel between the self and the world no longer exist.

Michael Pollan, in his incredible book How to Change Your Mind discusses how psychedelics allow us to reflect on memories and experience emotions in a novel way, exploring the contents of our unconscious mind. Pollan says our brain is normally so constrained and closed off, psychedelics help us expand our mind.

Ego dissolution is incredibly important therapeutically. A disordered, overbearing and punishing ego is at the core to mental illness. We get too attached the the narratives we create about ourselves and psychedelics can loosen that grip we have to them. This can create a more open self, allowing for a new sense of connection and self-discovery.

What does all of this mean? Psychedelic drugs hold astonishing treatment potential. They are anti-addictive and have minimal risk generally. Of course, these are not miracle drugs and the set and setting of the drug experience is immensely important. Taking psychedelics under the wrong circumstances can have extremely unsettling effects

Psychedelic research shows just how much of a mystery the mind still is and how difficult it is to treat mental illness. Indeed, depression is the single largest cause of disability worldwide— we have got to address this.

Unfortunately the legal status of psychedelic drugs has closed off many research avenues as there is no funding from government authorities. However, I think it is unethical not to conduct this research given the need for treatment and their incredible potential.

We are at the forefront of research to truly change our minds for the better and cure mental illness.

 
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Turn On, Tune In, Get Well

by Nathan Heller | The New Yorker | 5 Oct 2020

New York is getting its first psychedelic-medicine center, with the help of a startup called MindMed, which develops hallucinogens to treat mental illness and addiction, and is funding an institute at N.Y.U. Langone Medical Center.

J.R. Rahn, a techie whose company is helping fund New York’s first psychedelic-medicine center, spent the middle years of the past decade leading a successful startup while his life quietly came apart. “To the outside world, I was doing really well, but inside me I was struggling,” Rahn, a thick-built thirty-three-year-old with a shaved head, a smile-shaped beard, and delicate rimless glasses, said on Zoom the other day. He’d left New York to weather the pandemic in Miami; some palm fronds fluttered behind him. “People would say, ‘Oh, you’re just depressed.’ Well, I’m depressed, but I also can’t fall asleep without drinking a bottle of wine. I can’t have fun at a party without using cocaine.” Also, there was Xanax, for anxiety. Rahn needed help—or did he just need drugs of another kind? “A friend recommended I have a psychedelic experience, to piece together a solution,” he said. He did LSD and mushrooms a few times, and gave up all the other stuff.

Now Rahn is the co-founder of MindMed, a startup that develops psychedelic drugs to treat mental illness and addiction. In theory, such drugs are promising because they could be administered on a limited course (“like antibiotics,” Rahn says), in coördination with talk therapy—a contrast to addiction medications like methadone and Suboxone, and to many mental-health medications, which are often taken indefinitely. In practice, obstacles include the Timothy Leary factor (people still associate psychedelics with Ram Dass and British Invasion sitars) and the challenge of transferring lab successes to the therapeutic couch. “There’s really never been a precedent for using these substances within the psychiatric community,” Rahn said. “So how are you going to train the next generation of psychiatrists to take them seriously?”

One way is to train them at the training point. For years, researchers at N.Y.U. Langone Medical Center had been discussing the idea of a center for psychedelic medicine. MindMed just pledged five million dollars to N.Y.U. Langone, to kick off such an establishment, with the money earmarked for training. As the center-to-be settles the rest of its funding, its director, the psychiatry professor and addiction researcher Michael Bogenschutz, is preparing to bring aboard four junior faculty members and two postdocs: a New York team. (The first psychedelic-medicine center in the country, at Johns Hopkins, was created last year.)

“What distinguishes our effort is, you’ve got the practical focus on treatment of hard-to-treat psychiatric disorders front and center,” Bogenschutz said. The center will have no structural relationship with MindMed, but MindMed is looking to return its testing, now run by partners in Australia (tax incentives) and Switzerland (out-there medicine), to the U.S. for late trials.

In assessing drugs for study, Rahn was first drawn to ibogaine, a shrub-root derivative that had shown promise in addiction therapy. Unfortunately, at certain doses, it can lead to sudden death. Then Rahn’s co-founder, Stephen L. Hurst, turned him on to 18-Methoxycoronaridine, or 18-MC, a non-hallucinogenic relative of ibogaine that, in one study, helped rats stop eating cocaine and responding to Pavlovian triggers. The company is also running trials on LSD as a treatment for anxiety.

Rahn says that, for him, psychedelics opened his eyes to the source of his depression, anxiety, and substance abuse: his mother. “I discovered her dead on a vacation in the Dominican Republic as an eight-year-old child,” he said. It had not previously occurred to him that this might relate to his problems. “I think I probably got over the trauma, but what I didn’t get over was the guilt.”

Regarding the potential mental-health benefits of psychedelics, Bogenschutz notes, “What’s interesting is, why do people end up changing in a particular way as a result of a relatively brief experience?” So far, it’s unclear. “Our working model is that, because of an enhanced neuroplasticity, there is a temporary weakening of the established dominant networks that may keep people within a rigid pattern of behavior, such as drinking or ruminative thoughts,” he said. In addiction treatment, the effects sometimes last for years, suggesting a baking-in of new patterns—hence, in Bogenschutz’s view, the value of accompanying therapy.

In recent years, the market for psychedelic medicines, once a punch line, has become serious business. Compass Pathways, a psilocybin-centered company backed by Michael Novogratz and Peter Thiel, had its I.P.O. last month, and is listed on the Nasdaq. MindMed has filed Nasdaq papers, too, after noting clouds over the nation’s mental health. “I came to this realization that technology, A.I., this world I was in was about to displace a whole lot of people from work,” he said. “And, when people are displaced from work, rates of addiction and mental-health issues skyrocket.” The pandemic has darkened those skies further; prescriptions for anti-anxiety drugs leaped by a third in its first month. “Eleven per cent of Americans seriously considered suicide in June,” Rahn observed—a doubling since last year. “We’re not O.K.”

 
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New association brings psychedelics to the medical mainstream

by Justin Hampton | LUCID News | 9 Oct 2020

Psychedelics have entered the mainstream, informing a multimillion dollar industry – but the majority of healthcare providers working directly with patients are unaware of the growing field of psychedelic therapy. The newly formed Psychedelic Medicine Association (PMA) remedies this with a collaborative platform created for medical professionals, organizations, and drug developers to educate and guide each other over emerging science, ethics and cultural issues in this rapidly developing field.

PMA President Dr. Lynn Marie Morski says her mission is not to preach to the choir. According to her, "the organization is primarily aimed at those on the front lines of primary care. Those are the providers who need to learn about the psychedelic medicines that are currently or soon-to-be available so that patients can be made aware of their full range of options.”

When the PMA officially kicked off on September 29th with an hour-long webinar, Dr. Morski gave a sneak peek at the sorts of issues which will occupy the Association going forward.

At the conference, Numinus medical director Dr. Devon Christie spoke to her own background as a primary care physician, suggesting crucial opportunities of exposing primary care providers to psychedelic medicine, such as including it in their “rotations” during their final year in med school. Sean McAllister, executive officer of the Denver Psilocybin Mushroom Review Policy Board, spoke to extra-clinical settings such as the Decriminalize movement, and discussed the legal implications of off-label uses of psychedelics for “psychospiritual” purposes. Morski intends for these seemingly disparate agendas to co-exist within her organization while the PMA itself remains neutral.

“We believe that the first step is to create a framework for the conversation between key industry stakeholders, including many who will have opposing stances from each other. Therefore we will not be taking official positions on psychedelic use, we will solely be educating on the science behind their therapeutic uses,” Morski explains.

That said, the PMA is a signatory to the North Star Pledge, a guide of principles for the psychedelic industry, and Morski recently declared in the Psychedelic Therapy Podcast her intent to influence incoming psychedelic businesses by requiring they sign the pledge as a prerequisite for membership.

Since launching, Morski says she has several hundred members who are currently being processed and 30 organizations, including Fluence, Numinus, Maya Health, Field Trip and Heroic Hearts Foundation, amongst its members. Member dues comprise the bulk of funding for the PMA, which is organized as a social benefit corporation.

The PMA’s structure is designed for health care professionals to give direct feedback towards the companies making the medicines, rather than interfacing through sales representatives.

“Industry professionals will be offered the same fundamentals and a chance to speak with medical providers in an online community that will foster dialogue and help providers learn more about new psychedelic-based treatment options directly from those who are creating them,” says Morski. Her vision is that “organizational members will be able to recruit providers for clinical trials, gather data from providers on how therapeutic offerings are working, and offer training courses and workshops.”

In the coming months, Morski plans to extend her advisory board, which already includes Henri Saint-Cassia and Richard Skaife from the Conscious Fund and Dr. Kwasi Adusei, and bring new industry stakeholders into the fold, as well as to perform crucial outreach towards the primary care providers that are the Association’s strategic focus.

Maya Health CEO David Champion feels they’re off to a strong start. “In such a nascent industry it is essential to establish legitimacy, and I see the work Lynn Marie and her team are doing here as critical to that effort. I hope our Maya team can not only participate as fellow learners and community members, but also one day contribute what we’re learning, through our own research and data, to this group of pioneers in the field,” says Champion.

 
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The extraordinary therapeutic potential of psychedelic drugs, explained

by Sean Illing | VOX | 8 Mar 2019

I spent months talking to psychedelic guides and researchers. Here’s what I learned.

I had a close call on the second night of the ayahuasca ceremony. I saw my teenage self melting into particles and eventually disappearing altogether. I pulled off my sleep mask and saw the people around me shape-shifting into shadows. I thought I was dying, or perhaps losing my grip on reality.

Suddenly, Kat, my guide, appeared and began singing to me. I couldn’t make out the words, but the cadence was soothing. After a minute or two, the dread washed away and I settled back into a peaceful half-sleep.

The 12 of us — nine women and three men — taking ayahuasca in a private home in San Diego were led by two trained guides: Kat and her partner, whom I’ll call Sarah since she requested anonymity due to legal concerns. Together they have more than 20 years of experience working with psychedelics, including ayahuasca, a plant concoction that contains the natural hallucinogen known as DMT.

Kat (her full name is Tina Kourtney) and Sarah work as a team serving psychedelic medicine every month or so in a different city. Their primary role is to create a space in which everyone feels secure enough to drop their emotional guards and open up to the drugs’ potential to change their attitudes, moods, and behaviors.

There’s a lot of unease heading into these ceremonies, especially for people who have never experimented with psychedelics. The fear of what you might see or feel can be overwhelming. But guides like Kat are your port in the storm. When things get turbulent, they respond with a steady, calm hand.

Though psychedelic drugs remain illegal, guided ceremonies, or sessions, are happening across the country, especially in major cities like New York, San Francisco, and Los Angeles. Guiding itself has become a viable profession, both underground and above, as more Americans seek out safe, structured environments to use psychedelics for spiritual growth and psychological healing. This new world of psychedelic-assisted therapy functions as a kind of parallel mental health service. Access to it remains limited, but it’s evolving quicker than you might expect.

A majority of Americans now support the legalization of marijuana, and while a 2016 public poll on psychedelics suggested they aren’t as favorable, it’s possible that attitudes will shift as the research findings on their therapeutic potential enter the mainstream. (Author Michael Pollan’s 2018 book How to Change Your Mind, about his own experiences with psychedelics, helped spread the word. Even Gwyneth Paltrow has acknowledged their potential in a recent New York Times interview.)

But what would a world in which psychedelics are legal look like? And what sort of cultural structures would we need to ensure that these drugs are used responsibly?

Psychedelic drugs like LSD seeped into American society in the 1960s, and the results were mixed at best. They certainly revolutionized the culture, but they ultimately left us with draconian drug laws and a cultural backlash that pushed psychedelics into the underground.

Today, however, a renaissance is underway. At institutions like John Hopkins University and New York University, clinical trials exploring psilocybin as a therapy for treatment-resistant depression, drug addiction, and other anxiety disorders are yielding hopeful results.

In October, the Food and Drug Administration took the extraordinary step of granting psilocybin therapy for depression a “breakthrough therapy” designation. That means the treatment has demonstrated such potential that the FDA has decided to expedite its development and review process. It’s a sign of how far the research and the public perception of psychedelics have come.

It’s because of this progress that we have to think seriously about what comes next and how we would integrate psychedelics into the broader culture. I’ve spent the past three months talking with guides, researchers, and therapists who are training clinicians to do psychedelic-assisted therapy. I’ve participated in underground ceremonies, and I’ve spoken to people who claim to have conquered their drug addictions after a single psychedelic experience.

Our current laws sanction various poisons, including booze and cigarettes. These are drugs that destroy lives and feed addictions. And yet one of the most striking things about the recent (limited) psychedelic research is that the drugs do not appear to be addictive or have adverse effects when a guide is involved. Many researchers believe these drugs, when used under the supervision of trained professionals, could revolutionize mental health care.

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Turn on, tune in, and drop out?

The ’60s countercultural movement was transformational in many ways.

Among other things, it catalyzed the environmental movement, the civil rights movement, contemporary feminism, and the antiwar movement. But it also produced a decades-long backlash against psychedelic drugs that, until recently, made it almost impossible to conduct clinical research.

As late as 1960, psychedelics were fully legal and widely regarded as a promising line of psychological research. But just a few years later, the political and cultural winds had shifted so dramatically that the country was in a full-blown panic over psychedelics. In 1965, the federal government banned the manufacture and sale of all psychedelic drugs, and shortly thereafter, the companies making these drugs for research ceased production.

Michael Pollan gives an exhaustive account of this in How to Change Your Mind (a book I highly recommend), but the short version is that psychedelics could never escape the shadow of the countercultural revolution they helped spark.

Timothy Leary, the renegade psychologist and psychedelic evangelist who told kids to “turn on, tune in, and drop out,” is the familiar scapegoat. Leary, the argument goes, was too reckless, too confrontational, and too scary for the mainstream. Leary was such a threat that at one point, he was called the “the most dangerous man in America” by President Richard Nixon.

But Leary’s an easy mark and hardly the sole cause. The culture simply wasn’t ready for psychedelics in the ’60s. The experiences these drugs induce are so powerful that they can amount to a kind of rite of passage. But when they hit the scene, the population had no experience with them, no sense of their significance. As Pollan told me in an interview earlier this year, “Young people were having such a radically new kind of experience that the straight culture could not handle.”

Psychedelics were unleashed so fast that there were no cultural structures in place to absorb them, no containers or norms around them. Cultures around the world — from the ancient Greeks to the indigenous cultures of the Amazon — have been taking psychedelics for thousands of years, and each one developed rituals for them, led by experienced guides. Because there was no established community in the US, people were left to their own devices. When you combine this with a general ignorance about the drugs themselves, it’s not surprising that things went sideways.

But a lot has changed since the ’60s. The political and cultural landscape is radically different, and far more receptive to psychedelics. Rick Doblin, a longtime advocate for psychedelics and the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), made an interesting point to me when I sat down with him in Washington, DC, recently. (MAPS is a nonprofit research and educational organization that is leading the effort to promote the safe use of psychedelics.)

“In the ’60s,” he said, “the psychedelic counterculture was a direct challenge to the status quo ... it was about dropping out of the culture. Today, things like yoga and mindfulness meditation are fully integrated into popular culture. We’ve integrated spirituality and all these things that seemed so foreign and alien in the ’60s. So we’ve been preparing culturally for this for 50 years.”

At the same time, psychedelics may also play a role in addressing newer health threats like the opioid crisis. (70,000 Americans died of opioid overdoses in 2017, more than the total number of Americans that died in Vietnam.) They’re being used to treat populations like veterans suffering from PTSD, or cancer patients who are confronting their mortality, or people battling depression.

Psychedelics are becoming tools of healing rather than a threat to the social order. And the scientists and organizations and training institutions leading the way are working within the system to reduce the potential for blowback. This is very different from the approach taken in the ’60s, and so far it’s been a success.

Your mind on psychedelics

Psilocybin is the drug of choice for most researchers in recent years for a variety of reasons. For one, it carries less cultural baggage than LSD, and so study participants are more willing to work with it. Psilocybin also has strong safety data based on studies conducted before prohibition, and so the FDA has allowed a small number of small clinical trials to move forward.

Although the most recent studies are still preliminary and the sample sizes fairly small, the results so far are compelling. In one 2014 Johns Hopkins study, 80 percent of the smokers who participated in psilocybin-assisted therapy remained fully abstinent six months after the trial. By way of comparison, smoking cessation trials using varenicline (a prescription medication for smoking addiction) has success rates around 35 percent.

In a separate 2016 study of cancer-related depression or anxiety, 83 percent of 51 participants reported significant increases in well-being or satisfaction six months after a single dose of psilocybin. (Sixty-seven percent said it was one of the most meaningful experiences of their lives.)

A typical psilocybin session lasts somewhere between four and six hours (compared with 12 hours with LSD), yet it produces enduring decreases in depression and anxiety for patients. Which is why researchers like Roland Griffiths at Johns Hopkins believe psychedelics represents an entirely new model for treating major psychiatric conditions. Conventional treatments like antidepressants don’t work for a lot of patients and can come with a host of side effects.

This is a big reason why many researchers believe that psychedelics will eventually be rescheduled by the FDA (more on this below) and legalized for medical use — though the timeline on this is far from clear. In November, in fact, officials in Oregon approved a 2020 ballot measure that would allow medical professionals to conduct psilocybin-assisted therapy. If it passes, Oregon will be the first state to let licensed therapists administer psilocybin. Other states like California are likely to follow suit.

For more on the broad medical potential of psychedelics, I’d urge you to read my colleague German Lopez’s 2016 review of the science. Here I wanted to focus on how psilocybin works and why it’s so powerful for the people who take it. To understand the clinical side, I traveled to Johns Hopkins to sit down with Alan Davis, a clinical psychologist, and Mary Cosimano, a research coordinator and trained guide. Both help lead the psilocybin sessions at Hopkins.

Researchers at Hopkins have worked with a number of populations since they received approval from the FDA to study psilocybin in 2000 — healthy adults without any psychological issues, cancer patients suffering from anxiety and depression, smokers, and even seasoned meditators.

A key part of the process at Hopkins is what they call “life review.” Before they provide the drug, they want to know who you are, where you’re at in your life, and what kinds of emotional or psychological walls you’ve built up around yourself. The idea is to work with patients to determine what’s holding them back in their lives, and explore how they might overcome it.

Davis and Cosimano both say psilocybin has benefited every population they’ve worked with. “It’s not for everyone,” Cosimano told me, “but for the right person at the right time, it can be positively transformative.” (They don’t accept patients anywhere on the spectrum of psychosis — it’s just too dangerous.)

The psilocybin sessions are intense and, in some cases, last all day. The rooms they use are a curious blend of drab doctor’s office decor and New Age ornamentation. There’s a vanilla-colored couch covered with embroidered pillows and draped on both sides by South American art. Near the couch, on an end table, is a ceremonial cup and mini sculptures of magic mushrooms; it’s not quite an altar, but it may as well be.

The important thing, Cosimano and Davis say, is to make the patient as comfortable as possible. They even encourage people to bring personal artifacts with them, or letters from loved ones, or basically anything with deep emotional resonance. Much like the underground guides, researchers do everything they can to create a safe psychological space.

Sessions can unfold in multiple directions, depending on the depth of the experience (which is hard to predict) and the mental state of the individual. Mostly, patients are lying on the couch with a sleep mask covering their eyes. Cosimano, Davis, and other clinical guides act as lodestars — holding the patient’s hand and helping them process what they’re seeing and what it means. “I never get bored with this,” Cosimano told me. “Every single session is different, every experience is different, and I’m just blown away at being able to witness each person’s journey.”

Yet it’s not entirely clear to the scientists what it is about these experiences that produce such profound changes in attitude, mood, and behavior. Is it a sense of awe? Is it what the American philosopher William James called the “mystical experience,” something so overwhelming that it shatters the authority of everyday consciousness and alters our perception of the world? What’s clear in any case is that psychedelic trips are often beyond the bounds of language.

The best metaphor I’ve heard to describe what psychedelics does to the human mind comes from Robin Carhart-Harris, a psychedelic researcher at Imperial College in London. He said we should think of the mind as a ski slope. Every ski slope develops grooves as more and more people make their way down the hill. As those grooves deepen over time, it becomes harder to ski around them.

Like a ski slope, Carhart-Harris argues, our minds develop patterns as we navigate the world. These patterns harden as you get older. After a while, you stop realizing how conditioned you’ve become — you’re just responding to stimuli in predictable ways. Eventually, your brain becomes what Michael Pollan has aptly called an “uncertainty-reducing machine,” obsessed with securing the ego and locked in uncontrollable loops that reinforce self-destructive habits.

Taking psychedelics is like shaking the snow globe, Carhart-Harris said. It disrupts these patterns and explodes cognitive barriers. It also interacts with what’s called the default mode network (DMN), the part of the brain associated with mental chatter, self-absorption, memories, and emotions. Anytime you’re anxious about the future or fretting over the past, or engaged in compulsive self-reflection, this part of the brain lights up. When researchers looked at images of brains on psychedelics, they discovered that the DMN shuts down almost entirely.

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Think of it this way: You spend your whole life in this body, and because you’re always at the center of your experience, you become trapped in your own drama, your own narrative. But if you pay close attention, say, in a deep meditation practice, you’ll discover that the experience of self is an illusion. Yet the sensation that there’s a “you” separate and apart from the world is very hard to shake; it’s as though we’re wired to see the world this way.

The only time I’ve ever been able to cut through this ego structure is under the influence of psychedelics (in my case, ayahuasca). I was able to see myself from outside my self, to see the world from the perspective of nowhere and everywhere all at once, and suddenly this horror show of self-regard stopped. And I believe I learned something about the world that I could not have learned any other way, something that altered how I think about, well, everything.

At Johns Hopkins, the drug experience is only one part of the treatment. Equally important is the therapy that follows. People regularly tell researchers that the psilocybin session is the single most personally and spiritually significant experience of their lives, including childbirth and the loss of loved ones.

But there’s a need, Davis said, “to make sense of these experiences and to bring them into your day-to-day life in a way that doesn’t discount the meaning.” That doesn’t necessarily have to be therapy or one-on-one counseling with a guide, but it’s crucial to integrate the experience into your daily life, whether that’s taking up a new practice like yoga or meditation, spending more time in nature, or just cultivating new relationships.

The point is that’s it not enough to take the ride and move on; it’s about establishing new habits, new mental patterns, new ways of being. Psychedelics can kick-start this process, but for many people, at least, that’s all they can do.

When I returned from my first ayahuasca retreat, I struggled to process what had happened to me. I had no formal help, no instruction, no real support. It’s jarring to slide back into your routine after having your inner world turned upside down like that. I’ve adopted new practices (like meditation), and that has gone a long way in keeping me connected to that initial encounter with psychedelics, but there are limits to what you can do alone.

Recognizing the need for more integration, schools like the California Institute of Integral Studies and psychedelic researchers like NYU’s Elizabeth Nielson are focused on training professional therapists to work specifically with psychedelic users. Nielson is part of the Psychedelic Education and Continuing Care Program, which does not conduct psychotherapy but offers instruction to clinicians who want to learn about psychedelics.

“People who have used psychedelics, or will use psychedelics in the future, will need help integrating their experiences, and many will feel safest doing that in a therapist’s office,” she told me. “That means we’ll need more therapists who understand these experiences and know how to have these kinds of conversations with patients.”

In the meantime, we’ve seen a parallel growth in a more informal support system for people experimenting with psychedelics, one that exists mostly underground.

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Psychedelics and the underground

For decades, a community of guides has worked quietly in the shadows, serving psychedelics to people across the country. And they’re not that different from their above-ground counterparts — or at least not as different as you might expect. Many of them have spent years apprenticing under traditional healers in places like Peru and Brazil and follow a strict code of conduct designed to formalize practices and ensure safety.

This was certainly true of Kat, the guide I sat with in San Diego. She studied under a Peruvian mentor for eight years and estimates that she’s used ayahuasca more than 900 times and led hundreds of ceremonies in Europe and the US.

She calls herself a “tone setter,” someone who controls the space. Mostly, she puts everyone at ease by projecting a calm and reassuring presence. “I take the pulse of the room, and when I have to go over to somebody, I try to be as grounded as the earth itself — that sort of calmness is contagious,” she said. “The key thing is to be attuned to what’s happening and how people are feeling, and respond to that.”

Her role is a tightrope walk between letting people go through whatever they’re going through and intervening when they’re too close to the abyss. If everyone’s fine, she’s somewhere in the room singing medicine songs and keeping a watchful eye on things. If someone panics, Kat must talk them down, and do it in a way that doesn’t overwhelm everyone else in the room.

Just a few months ago, she told me, a woman at one of her ceremonies was convinced demons had taken over her body. She became hysterical and threatened to call 911. Situations like this arise all the time, and the guide has to figure it out on the fly.

Unlike the clinicians at Hopkins, Kat manages the trips of multiple people at a time, sometimes dozens, and that carries risks. I asked her, why do this? Why risk managing someone reacting in ways she can’t control, or risk going to jail?

“Because it heals people,” she told me. “I see it every time I hold a circle, every time I walk a group of people through this experience. People enter with one perspective and leave with another. Sometimes that means they see the world with new eyes, and sometimes it means they realize they’re more than their addiction, that their flaws don’t define them.”

Kat, now 43, has had plenty of her own battles. Before discovering ayahuasca 13 years ago on a trip to Peru, she had alcoholism, bulimia, and bipolar disorder — at one point, she attempted suicide. “The medicine wasn’t a panacea,” she said, “but it set me on a different path, and basically I dedicated my whole life to this work.”

She tried traditional therapy for several years, mostly to treat her bipolar disorder and bulimia. When that failed, she dabbled in self-help workshops, from Radical Awakening seminars to Mastery in Transformational Training courses. “I was obsessed with finding some sort of relief,” she told me, “but nothing worked, nothing stuck.”

Everyone who shows up at Kat’s ceremonies has their own reason for being there. Some are psychonauts — people looking to explore altered states of consciousness through the use of psychedelics. Others, like Laura, a 35-year-old woman from Philadelphia, are drawn to plant medicine as a last-ditch effort to conquer an addiction.

In Laura’s case, it was a 14-year addiction to heroin. “I was at the edge of death. I tried every conventional method you can think of — detox, counseling, rehab — and nothing worked,” she told me. She eventually found ibogaine, a psychedelic compound derived from the roots of a West African shrub. “Ibogaine was like a myth on the streets, this miraculous modality that could reset your brain and save you from the throes of addiction.”

Laura told me that she eventually went to her family and said: “Put a gun in my mouth and pull the trigger or send me to an ibogaine clinic.” They sent her to an ibogaine treatment center just north of Cancun, where she did a few sessions. She has now been clean for the past eight years.

Ibogaine is not as well researched as psilocybin or LSD, and it’s comparatively dangerous, but it’s one of the most powerful known psychedelic drugs, and there is preliminary research suggesting it may be an effective treatment for opioid and cocaine addiction.

Another woman, a 48-year-old from Kansas whom I’ll call April, told me she spent 15 years hooked on Adderall, a stimulant prescribed for attention deficit hyperactivity disorder. “It consumed my entire life — every decision, every plan, basically every moment.” She tried several times to quit, but the withdrawal was too much. On a whim, she decided to look into psychedelics and found her way to Kat’s website. A few weeks later, she was sitting in a ceremony.

Her first ayahuasca trip was in September, nearly three months ago, and she hasn’t touched Adderall since. “The experience was rough,” she said. “It was like seeing myself and my life through a funhouse mirror, and I could see all the masks I wear, how Adderall had become this crutch, this source of false energy that propelled me through my life. I feel like it recalibrated my whole being.”

These stories are inspiring, but it’s not clear how representative they are. Psychedelics aren’t a magic elixir, and there are physical and psychological risks to taking them haphazardly, particularly if you’re on medication or have been diagnosed with a psychiatric condition. But used in a proper setting with a trained guide, they can be remarkably therapeutic. (As far as I know, there are no documented “bad trips” in the research literature.)

Kat believes this work could be more impactful if it wasn’t forced underground. “If this was legal, I’d spend more time with people before and after the experience. I’d want to build up my team and do this aboveground like a normal business and take care of people from start to finish. Because we’re in this legal gray area, people often come into the ceremony and then they’re shot right back into the world, and that can be traumatic.”

I asked Kat if she’s noticed a shift in the sorts of people attending her ceremonies. It used to be mainly the psychonauts, she told me, but lately it’s people, old and young, who want to make peace with mortality or face down deep traumas. She’s working with more and more veterans struggling with PTSD, many of whom tell her they failed to find relief from traditional mental health care.

Still, she hesitated when I asked her about legalization. “They should absolutely be legal, but I’m not sure they should be legal tomorrow,” she said. “We need a firm foundation in place, a way to keep the reverence around these medicines. If we lose that, if psychedelics become another substance like marijuana, I worry that we’ll blow this up and burn it down like we did in the ’60s.”

Kat’s concern, shared by many people in this space, is that the ceremonial aspects around psychedelics will be lost if they’re legalized overnight. There’s nothing inherently wrong with recreational use, but for those who regard psychedelics with a kind of sacred awe, there’s a genuine fear that these substances will be trivialized if we don’t make this transition wisely.

So how do we integrate psychedelics into the culture?

For better or worse, psychedelics, like all drugs, are going to be used outside the safer contexts of research facilities or private sessions with experienced guides. According to Geoff Bathje, a psychologist at Adler University who works with high-trauma patients, the question is therefore, “What sort of harm reductions do we need to help protect people?”

Several people I spoke with pointed to the “harm reduction” model. Harm reduction focuses on reducing the risks associated with drug use, as opposed to punitive models aimed at eliminating use altogether. It’s a practical and humane approach that has worked well in places like Portugal, where all drugs for personal use have been decriminalized.

Although the harm reduction model isn’t typically associated with psychedelics, the principles apply all the same.

For Bathje, it’s about doing good drug education in the general population, “making sure people understand the risks involved with psychedelics — how they can be misused, how people can be exploited when under the influence, etc.” There are already national harm reduction groups like Zendo Project, which is sponsored by MAPS, that focus on peer-to-peer counseling for people experimenting with psychedelics.

Bathje and some of his colleagues have established a harm reduction group in Chicago called Psychedelic Safety Support and Integration. The goal is to promote safety and help people process their psychedelic experiences. It’s a critical container that brings in the community, spreads awareness of the risks associated with psychedelic drug use, and creates a space for connection.

At the moment, there’s a gap between the harm reduction movement and the psychedelic research community. “You go to a psychedelics conference and it’s focused on the science and the therapeutic potential,” Bathje said, “and the general assumption is that if we just produce good science, these drugs will get approved as medicines and everything will just fall into place.”

“If you attend a harm reduction conference,”
he added, “it’s all about cultural change and how politicians don’t care about the science. The focus is much more on organizing and who has the power and how we can reduce risks and do things safely.” This is partly why the harm reduction movement can be useful to psychedelics. Science may be critical to legalization, but public health programs would have to help integrate these drugs into the broader culture.

Harm reduction groups like Bathje’s and the Zendo Project are the best models we have for this sort of integration, and we’d need to scale them up if psychedelics are legalized for medicinal use.

There are reasons to be cautious, but we should welcome the evolution of psychedelic research

After spending months thinking about these issues and talking to people involved at nearly every level, I’m convinced that the new culture of therapeutic psychedelics is evolving quickly. Just this week, a group of citizens in Denver gathered enough signatures to approve a ballot measure in the spring that would decriminalize magic mushrooms.

As Rick Doblin pointed out, the social and political milieu is much different today than it was in the ’60s, and there’s no reason to suspect a similar backlash. The cultural containers and the knowledge are there, and they could increasingly be brought out of the shadows.

What this transition on a larger scale will look like, and how long it will take, is less clear. Advocates like Doblin seem wise to continue playing the long game. Given the progress of the research, it’s possible that psilocybin will be recategorized from a schedule 1 drug (drugs with no known medical value) to a schedule 4 drug (drugs with a low potential for abuse and a known medical value) in the next three or four years.

The process of rescheduling drugs, however, is a bit muddled. Under federal law, the US attorney general can move to reschedule drugs on their own, but they are required to gather data and medical research from the secretary of health and human services before doing so. Congress can also pass laws to change the scheduling of drugs, and could, if they chose, overrule an attorney general.

We’re unlikely to see much progress on this front under the current administration, but the political winds can shift in a hurry, especially if the research continues apace. That the Drug Enforcement Agency is already comfortable with the possibility of rescheduling psychedelics is a very positive sign.

“We’re happy to see the research progressing at institutions like Johns Hopkins,” Rusty Payne, the DEA’s spokesperson, told me in a phone interview. “When the scientific and medical community come to the DEA and say, ‘This should be a medicine, this should be recategorized as a schedule 4 or 5 instead of a schedule 1’; then we will act accordingly.”

Support for psychedelics is also one of those rare issues that can, in some cases, cut across conventional political lines. Rebekah Mercer, the billionaire Republican financier and co-owner of Breitbart, has donated a $1 million to MAPS to fund their studies focused on veterans with PTSD. As the research advances, we could see more bipartisan support like this.

One big remaining question has to do with access. If you spend any time at all in the psychedelic subculture, you can’t help but notice that it consists mostly of privileged white people. This is largely a product of who’s holding these spaces, how much they cost (anywhere from $600 to well over $1,000 per session), where they’re being held, and the networks of people propping them up. That many people simply don’t know about the therapeutic potential of psychedelics is yet another barrier. All of this has to change, and hopefully it will when psychedelics aren’t relegated to the underground.

Within the psychedelic community itself, there are concerns about commodification. Companies like Compass Pathways are seeking to turn psilocybin into a pharmaceutical product. (Compass’s psilocybin study is the one that received the breakthrough therapy designation from the FDA in October.)

Compass began as a nonprofit venture with an interest in starting a psychedelic hospice center but has since pivoted to a for-profit approach. With major investors like Peter Thiel behind it, Compass might dominate the medical supply chain of psychedelics from synthesis to therapy. It’s also impeding the research efforts of nonprofit companies like Usona that are developing their own psychedelic medicines. If the market becomes monopolized, or if a few pharmaceutical companies control critical patents, lots of people could be priced out of access.

Despite all these concerns, we should welcome the evolution of psychedelic research. We need bigger studies, and we need to include more diverse populations in them to learn as much as we can about how these drugs work. As Richard Friedman, a clinical psychiatrist at Cornell University, told me, “I’m all for optimism, but show me the data. I embrace the enthusiasm for the therapeutic potential of psychedelics ... but as to whether it’s justified, the answer will be the data. And nothing but the data.”

So far the data is encouraging, yet there’s plenty we don’t yet understand. But we know enough to say that psychedelics are powerful tools for reducing suffering at least for some people. And we simply don’t have enough of these tools to justify their prohibition.

 
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Psychedelics: Overlooked clinical tools with unexplored ergogenic potential

by Steven B. Machek, Department of Health, Human Performance, and Recreation; Exercise and Biochemical Nutrition Laboratory; Baylor University, Waco, TX [2019]

Abstract

Psychedelics are a stigmatized, under-researched class of psychedelic drugs with unprecedented boundless potential. Despite a historically widespread cultural use, these drugs were denigrated and prematurely banned before clinical trials could demonstrate their value. It is now known that through full or partial serotonergic receptor agonist activity, psychedelics impart positive effects on a broad spectrum of psychiatric disorders including depression, anxiety, post-traumatic stress disorder, and obsessive-compulsive behaviors. Furthermore, extremely small, non-intoxifying microdosed psychedelics (1/10th-1/16th typical dose) may potentiate similar effects to full doses without undesirable side effects. These compounds are also unexplored for their potential role in physically active populations. A preponderance of subjective claims and fervent anecdote indicate psychedelics may enhance mental acuity and subsequent exercise performance. Through the same serotonergic-mediated mechanisms that invoke neuroplasticity, psychedelics possibly augment exercise adaptation and offer safer alternatives to current pain management strategies. Despite a wealth of promising clinical data and high drug safety, federal restriction remains a psychological barrier to research and general public acceptance. Therefore, the purpose of this short review is to 1) briefly demonstrate the clinical value of psychedelics, and 2) highlight the potential of microdosing as an effective alternative to full-dose psychedelics whilst emphasizing their latent ergogenic ability.

Background


Originally coined by Humphrey Osmond in 1957, the term “psychedelic” denotes mind-manifesting capabilities and hidden properties of the brain. As a class of psychedelic drugs, psychedelics encompass a bevy of compounds, including –but not limited to –lysergic acid diethylamide (LSD), psilocybin, mescaline, and N, N-dimethyltryptamine (DMT). Historically, several cultures have utilized psychedelics in sociocultural and ritualistic contexts. Psilocybin-containing mushrooms were used by the Aztecs in healing and religious rituals. The peyote cactus and its active psychedelic component, mescaline, were used as religious sacrament in the Native American Church. DMT has an extensive history in the Amazon valley of South America; natives brewed DMT-containing ayahuasca from the crushed bark of Banisteriopsis caapi and the leaves of Psychotria virdis. Regardless, these compounds were subject to scrutiny during periods of political unrest in the United States. Similar to cannabis at that time, psychedelics became a scapegoat for antiwar sentiments and rebellious attitudes, resulting in the Controlled substance act of 1970. This policy severely restricted psychedelics before sufficient research could surface to display their latent therapeutic potential. While sparse, the existing and growing psychedelic literature is optimistic. A dwindling stigma and concomitant improvements in public perception has motivated research to demonstrate the clinical value of psychedelics in populations from the depressed to the terminally ill. Several of these compounds are characterized for their ability to invoke neuroplasticity, resulting in profound effects on mood and anxiety. Beyond the clinical realm, otherwise healthy demographics are beginning to experiment with extremely small “microdoses” of psychedelics to improve their cognitive performance. Microdoses commonly entail subthreshold doses of psilocybin (0.1-0.5 mg) or LSD (6-25 μg) in lieu of full-fledged administration (6-20 mg and 75-150 μg for psilocybin and LSD, respectively). Despite their immense potential, psychedelics are heavily under-researched in human populations, require extensive subject screening, and are not without risk. Therefore, the purpose of this short review is to 1) briefly demonstrate the clinical value of psychedelics, and 2) highlight the potential of microdosing as an effective alternative to full-dose psychedelics whilst emphasizing their latent ergogenic ability.

Benefits of psychedelic use

While not fully elucidated, it appears that psychedelics function as serotonergic agonists or partial agonists. Several psychedelics, including psilocybin, LSD, DMT, and mescaline are structurally similar to 5-hydroxytryptamine (serotonin) and have high affinity for the serotonin 2A (5-HT2A) receptor. Primarily through 5-HT2A activation-mediated mood regulation, psychedelics impart effects on cognitive flexibility and associative learning, as well as exerting anti-depressive and anxiolytic properties. Additionally, there is evidence that psychedelics can attenuate obsessive-compulsive and post-traumatic stress disorder (PTSD) tendencies. Generally, psychedelic compounds like psilocybin have displayed an intriguing ability to reduce cerebral blood flow to areas of the brain tasked with social attributions, waking consciousness, and self-reflection. This reduction is hypothesized to accompany increased connectivity between brain regions (that normally function independently) to reduce depressive symptoms. Given these mechanisms, psychedelics may fit a unique role in treating psychiatric disorders. An investigation by Carhart-Harris et al. utilized an acute 25mg psilocybin dose in patients with treatment-resistant depression, where ultimately all patients showed a reduction in symptom severity. Surprisingly, this attenuation persisted at 3-months post-intervention. The long-term psychological benefits are corroborated by Griffiths et al., who investigated the impact of psilocybin on patients concurrently suffering from life-threatening cancer and clinical depression. Treated subjects saw acute improvements in subjective well-being and life satisfaction that persisted six months following a single high-dose.

Mood and anxiety disorders are a United States epidemic and economic burden. Shockingly, depression annually costs the nation $200 billion on clinical treatment. Patients suffering from depression are commonly prescribed selective serotonin reuptake inhibitors and benzodiazepines, which are subject to diminished returns and withdrawal, respectively. Conversely, psychedelics display no tendency for dependence or addiction. Psychedelics have even been touted for their ability to ameliorate addiction of drugs such as tobacco and alcohol. Daily use of psychedelic substances is not habit forming due to rapid 5-HT2A receptor downregulation, a phenomenon deemed tachyphylaxis. Persistent alcoholism and nicotine addiction are linked to altered serotonergic activity in the brain and an increased 5-HT2A receptor density. Ostensibly, psychedelic-mediated 5-HT2A receptor activation facilitates drug rehabilitation by exerting “mystical” subjective effects that promote acute enhancement in therapeutic suggestibility. Subsequent rapid downregulations in 5-HT2A receptor density further operate to prevent drug relapse. Unlike standard allopathic approaches, psychedelics are devoid of insidious, chronically damaging side effects. They have an extremely low risk of overdose, and a lethal administration is between 100-to-1000 times an effective quantity. Most undesired effects following acute administration are transient, including increases in (systolic and diastolic) blood pressure, as well as altered spatial working memory, delayed temporal perception, and slowed reaction time. Opponents of psychedelics are often concerned with psychedelic effects and subsequent alterations in behavior. Colloquially known as a “bad trip”, an improper dose of psilocybin, LSD, and other psychedelic compounds may result in extremely traumatizing experiences. Users have reported acute fleeting symptoms (i.e. dizziness, weakness, drowsiness, and dysphoria), but also more prominent feelings of fear, anxiety, and paranoia. Frightening illusions, distressing self-thoughts and even an awareness of a perceived “greater evil” may also manifest. These episodes are uncommon and typically occur from ingesting high relative doses and/or unfavorable associations with the user’s environment. Nevertheless, psychedelic use should be heavily cautioned in those with previous psychiatric disorder and/or with concurrent serotonergic-mediated medications.

Microdosing practice

First introduced in James Fadiman’s “The Psychedelic Explorer’s Guide”, microdosing is the practice of ingesting a very low dose of a psychedelic. Typically, a small dose (around one-tenth to one-sixteenth) of psilocybin or LSD is used, resulting in little-to-no identifiable acute drug effects. Microdosing may represent a method to actualize many of the benefits of psychedelic compounds without potentially deleterious intoxication. The practice has become extremely popular in mainstream media, with proponents claiming enhanced vitality, creativity, productivity, social ability, focus, analytic thinking, positive mood, memory, and general wellbeing. Many self-reports also claim that microdosed psychedelics are capable of clinical benefits similar to a full-fledged dose, attenuating symptoms of depression, anxiety, pain, as well as reducing PTSD-related and obsessive-compulsive behaviors. Catlow et al. previously demonstrated thatlow dose psilocybin administration (0.1 mg/kg for 1 month) in mice led to 5-HT2A-mediated increases in hippocampal neurogenesis and trace fear extinction, ultimately suggesting a reversal in PTSD-associated fear conditioning. Cameron et al. similarly found enhanced fear extinction in rodents administered low-dose DMT (0.1 mg/kg every third day for two weeks). Purported improvements in fear extinction may have future implications in clinical PTSD treatment, or perhaps in rehabilitation settings to restore normal movement after debilitating injury. While not fully elucidated, psychedelics may attenuate obsessive compulsive behaviors by rapidly inducing 5-HT2A receptor downregulation. Clinical manifestations of obsessive compulsive disorder are characterized by an upregulation in 5-HT2A receptors due to serotonin insufficiency and subsequent negative feedback between the thalamus, orbitofrontal cortex, the caudate nuclei, and the globus pallidus. Although microdosing mirrors many of the purported benefits of full-dose psychedelics, there is a stark paucity of literature investigating its efficacy. Regardless, psychedelic microdoses have gained traction in the general population as a means of augmenting work performance. Unlikely users, including students and Silicon Valley workers have adopted microdosing to gain a competitive advantage through enhanced work efficiency.

Ergogenic potential of full-dose & microdosed psychedelics

It may be pragmatic to view microdosed psychedelics as nootropics, or compounds used to enhance cognitive function. Nootropics are becoming an increasingly popular method to gain a cognitive edge in competitive environments. Adderall (amphetamine) and Ritalin (methylphenidate) are illicitly used to improve work efficiency and focus, disregarding addictive potential or risk of psychological dependence. The impetus to augment performance with precarious stimulant use is further present in the sports realm, where athletes are willing to risk their careers and health to gain an edge. Apart from inherent clinical value, psychedelic compounds might serve as a novel ergogenic aid in lieu of precarious stimulant use. To the author’s knowledge, no literature has investigated the effects of psychedelics on mental acuity in athletic settings. Curiously, historical reports give credence to this notion, whereby ancient Greek Olympic athletes consumed psilocybin mushrooms as a means to enhance performance. For nearly five decades, clandestine extreme sportsmen have used psychedelics in microdoses for their so-called “psycholytic” effects. They attest to improvements in stamina, reflex time, and balance. Athletes participating in extreme snowboarding, mountain-biking, surfing, and various other sports describe how psycholytic doses of LSD and psilocybin can facilitate an unparalleled focus, whereby time slows to their advantage and coordination becomes effortless. Notably,professional baseball player, Dock Ellis, pitched a no-hitter under the influence of LSD; a task deemed nearly insurmountable considering the extensive history of baseball. Notwithstanding these astonishing anecdotes, researchers have neglected the ergogenic potential of psychedelics in athletes. While there is no clinical literature investigating the effects of psychedelics on enhanced cognitive function, there is a mechanistic basis to suggest 5-HT2A receptor agonist (or partial agonist) activity plays a beneficial role in working memory. Furthermore, rodents administered mescaline demonstrated robust increases in the neurotransmitter, acetylcholine. It is important to emphasize that these drugs not only lack addictive potential, but also impart several qualitative effects valued amongst athletes. A wealth of survey-based subjective descriptions claim enhanced focus, vitality, and productivity, lending the potential to facilitate greater training quality across all exercise modalities. Lastly, psychedelics may find a supplementary role to caffeine. As a ubiquitous stimulant, caffeine has extensive evidence as an ergogenic aid to enhance athletic and cognitive performance. However, chronic use results in addiction, tolerance, and diminished effects. Psychedelics may improve athletic performance without risk of tolerance whilst simultaneously acting to attenuate caffeine addiction. Given the propensity of subjective psychedelic benefit, microdosing practice warrants further investigation on its ability to augment athletic endeavors.

Psychedelics also have a largely unexplored impact beyond neural physiology. Administration of microdosed DMT has shown increased rates of non-adipose weight gain in male rodents, which may indicate accretion of skeletal muscle or connective tissue. Activation of the 5-HT2A receptor stimulates the mammalian target of rapamycin (mTOR), promoting rapid growth of dendritic branches, spines, and synapses. The mTOR pathway is heavily studied in exercise science as a master regulator of muscle growth. Nevertheless, it is unknown whether psychedelic-mediated stimulation of this pathway may facilitate the accretion of contractile proteins. The extracellular regulated kinase 1/2 (ERK1/2) and p38 pathway are also activated in response to 5-HT2Aagonist action; these cassettes of the mitogen-activated protein kinase family play significant roles in cell proliferation and survival. Commonly discussed in exercise adaptation, ERK1/2 crosstalks with the mTOR pathway, facilitating muscle growth independent of ERK1/2-specific effects. On the other hand, the p38 pathway may exert hypertrophic-associated effects by increasing phosphorylation and subsequently inactivating the MRF4 myogenic regulatory factor, which is involved in the late stages of myogenesis and adult skeletal muscle maintenance. Inactivation of MRF4 promotes proper cellular differentiation via cell cycle withdrawal. Further research is required to uncover the utility of full-dose and microdosed psychedelics in serotonergic agonist-mediated lean mass modification. Perhaps these compounds play a dualistic role in potentiating the molecular responses to both neurogenesis and molecular exercise adaptation.

Finally, psychedelic compounds may facilitate pain management in both athletes and the general population. Subjective survey data indicates users commonly employ psychedelics for pain reduction. Furthermore, anecdotal reports from extreme sport athletes claim psycholytic doses of LSD make them impervious to pain and fatigue. These analgesic properties may be due to psychedelic-induced reductions in tumor necrosis factor alpha (TNF-a)-mediated inflammation across various tissues. TNF-a and several other pro-inflammatory cytokines are implicated in the initiation and persistence of chronic pain via activation of nociceptive neurons. Additionally, serotonin is thought to play a role in pain perception and 5-HT2A receptor agonist activity has demonstrated anti-nociceptive effects in non-human primates. Incessant pain is common in the general population and extremely prevalent in athletes, frequently leading to drug abuse. Athletes obtain over-the-counter and prescription non-steroidal anti-inflammatory drugs (NSAIDs) to manage minor aches and injuries, however there is evidence that NSAIDs delay the tissue healing process by inhibiting pro-inflammatory prostaglandin synthesis. For chronic and serious injuries, opiates may be prescribed to provide greater pain relief. These powerful drugs warrant extreme regulation, however, due to their highly addictive nature and causal relationship to drug-related mortality. Therein lies a novel position for psychedelics to augment existing pain management strategies: psychedelics have a propensity to attenuate pain symptoms without risk of inhibiting recovery or developing addiction. Furthermore, comparable to effects in alcohol and tobacco, psychedelics may assist in addiction recovery following opiate prescription. Opiate addiction is characterized by increased serotonergic activity in various areas of the brain, whereby psychedelic-mediated rapid 5-HT2A receptor downregulation may attenuate dependence. The overall utility of full-dose and microdosed psychedelics as analgesics are in desperate need of further investigation. Similar to their potential efficacy in psychiatric illness, these compounds may represent a safer alternative and/or preemptive treatment to standard, allopathic approaches.

Final remarks

Considering their potential to facilitate treatment in a variety of extremely prevalent national health issues, it seems rational to reconsider the role of psychedelics in society. A small number of cities in the United States have started a paradigm shift by decriminalizing psilocybin mushrooms and loosening regulation on distribution, consumption, and possession. Nevertheless, likely due to their legal status, data on the human physiologic response to psychedelics remains scarce. Statutory restrictions foster risk of illicit acquisition and the potential purchase of contaminated products. Additionally, the mercurial “bad trip” is largely uninvestigated and behavioral impacts of unregulated psychedelic use remain a concern amongst the general population. Microdosing small, non-intoxifying doses of these drugs may be the answer to reconcile the issue, but time alone will tell. Therefore, future research is tasked with elucidating the impacts of acute and long-term psychedelic administration in varying doses, as well as establishing appropriate subject psychiatric screening methods. With sufficient evidence, the decriminalization of psilocybin mushrooms may catalyze a paradigm shift where the full clinical potential of psychedelics may be realized.

*From the article here :
 
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Who will benefit from psychedelic medicine?

by Whitney Joiner | Washington Post | 21 Sep 2020

These substances are being touted as a game-changing intervention for mental health. But it’s not clear if their promise will be accessible to all.

On a sweaty Sunday morning in August of last year, Jamilah George was on the 16th floor of the historic Brown Hotel in Louisville, leading a spiritual service of sorts. George, a doctoral candidate in clinical psychology at the University of Connecticut who also holds a master’s degree in divinity from Yale University, asked the audience to shout out the names of ancestors or people they admired. With each name, George performed a libation ritual, pouring water into a leafy green plant, stationed at the front of the podium, as a gesture of thanks. “Maya Angelou,” called out one audience member. “Mama Lola,” called another. The names kept coming: Toni Morrison. Audre Lorde. Mahatma Gandhi. Harriet Tubman.

George, who had been part of a team at U-Conn. running the only clinical trial to study the effects of the psychotropic drug MDMA on post-traumatic stress disorder with participants of color, wanted the audience to connect with its cultural lineages before she started her presentation — a bracing call for inclusion and social justice within the burgeoning world of psychedelic healing. It’s a world that holds great promise but is overwhelmingly White and economically privileged. Part of the problem, as George sees it, is that academia has lost its connection to the histories of these consciousness-altering substances (also known as entheogens), many of which have been used by Indigenous cultures for physical and psychological healing for thousands of years.

“It’s up to us to find ways to disseminate resources and stop leaving them at the top, in the most elite research institutions,” she said to the small audience of psychotherapists, who were there to learn how psychotropic substances like methylenedioxymethamphetamine (MDMA) and psilocybin, the active ingredient in hallucinogenic (“magic”) mushrooms, could be used to heal mental and emotional distress. “We have to find ways to take this information and bring it down so it’s accessible,” she continued. “MDMA — you can’t even pronounce it! We have to find ways to make this information translatable. It’s like speaking another language.”

The next day, the public part of the inaugural Psychedelic Medicine & Cultural Trauma Workshop ended and the psychotherapist training began. Fifty therapists of color had been accepted into the week-long training, hosted by MAPS, the Multidisciplinary Association for Psychedelic Studies. In the training, therapists would learn best practices for using the entheogen MDMA to treat PTSD in their patients.

MAPS is currently studying MDMA-assisted psychotherapy as a method of treating PTSD. The clinical trials are in Phase 3 — the last stage before approval from the U.S. Food and Drug Administration — and MAPS, which has been working toward this moment since its inception as a research and advocacy organization in 1986, has been preparing for a post-approval world. Before the Cultural Trauma workshop in Kentucky, MAPS had trained 285 therapists, with the idea that — while they can’t legally practice yet — they will be ready to open their doors once approval is final. But fewer than 10 percent of those trained were people of color. If MAPS wanted therapists to treat clients of color, they would need to train therapists of color.

Last year, there were at least 20 conferences in the United States covering the latest developments in psychedelic science and medicine. It’s a conference-happy community, which makes sense: Most of the substances discussed at these events are labeled as Schedule 1 or 2 by the U.S. Drug Enforcement Administration, so, outside of clinical research, their use is illegal. (Schedule 1 drugs are considered to have the highest potential for abuse, with “no currently accepted medical use.” MDMA is a Schedule 1 drug, as is cannabis, and is ranked as more dangerous than oxycodone and cocaine, which are both Schedule 2.) Conferences are one of the few places where researchers, clinicians, advocates and the curious public can learn about developments in the field and meet other psychedelic proponents. Compared to a huge event like New York City’s Horizons: Perspectives on Psychedelics conference, which has convened every fall in New York for 13 years and last year brought in over 2,800 attendees, the two-day public workshop in Kentucky was tiny, with fewer than 100 participants and very little attention from a media that energetically covers psychedelic developments.

But the gathering — which featured talks on drug legalization and systemic racism, presentations on Indigenous healing methods, experiential group exercises, and even a dance performance — was groundbreaking. It was historic not only because it was the first such training for therapists of color, but because it marked a turning point in the mainstreaming of psychedelics. Many of the organizers and presenters are part of a larger effort to diversify the world of psychedelic healing. They are pushing back against the popular narrative that psychedelics originated in White, mid-century countercultural movements and, perhaps most significant, fighting to ensure that the new field of psychedelic medicine — often touted as a miracle for long-standing and deep-rooted struggles like treatment-resistant depression, addiction, anxiety and PTSD — will be accessible to all. This includes Black and non-White communities that have been historically over-policed and heavily incarcerated for possession or sales of some of these substances. (White people and Black people are equally likely to use illegal drugs, a 2009 Human Rights Watch report found, but Black people are arrested for drug offenses at much higher rates than White people.)

George, who is Black, spoke directly to these inequities at the climax of her talk. While White people might see psychedelic use as edgy or controversial, there is little legal risk in White use of these substances. “Western researchers have taken some of these Indigenous religious traditions, using them outside of their spiritual context ... and then take it for ourselves and go to a rave and jump around and flash the lights,” George said. “We go in the mountains and have a self-discovery kind of experience.” Her voice rose as audience members clapped in agreement. “All of that is amazing. Let’s do that. But let’s bring others with us. Let’s find ways for those who have been oppressed for generations to experience the same freedom that some of us in this room have on a Saturday morning because they feel like it. Not on a Tuesday night when they’ve had to take off work and find a babysitter to take care of the kids so they can come to the clinic and participate in this research and pray that it frees them, so they can keep their families and keep their jobs.”

She continued: “Lives depend on us. You see what I’m saying? When you really think about it, when you break it down like that, lives depend on us.”

There is little legal risk in White use of psychedelic substances. But Black and non-White communities have been historically over-policed and heavily incarcerated for possession or sales of some of these substances.

It would be hard to avoid coverage of what’s been called “the psychedelic renaissance”: It’s everywhere. In a recent episode of “60 Minutes,” Anderson Cooper reported on successful clinical trials at Johns Hopkins and New York University that found psilocybin can help with, respectively, smoking cessation and binge drinking. Gwyneth Paltrow’s Netflix show “The Goop Lab” dedicated an episode to following Goop employees at a healing psilocybin retreat in Jamaica, where mushrooms are legal. And, of course, there’s science journalist Michael Pollan’s No. 1 New York Times bestseller “How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence.” The politics around psychedelics are changing as well: With great effort from advocates, various measures to decriminalize possession of certain entheogens have passed in Oakland and Santa Cruz, Calif., as well as Denver, and similar campaigns are underway in Chicago and other cities. In November, this movement will come to D.C., when residents will vote on whether to decriminalize magic mushrooms.

Entheogens like peyote and ayahuasca have been used within Indigenous cultures for thousands of years, but this latest wave of research has mostly focused on two substances: MDMA, a derivative of the sassafras tree, which was first synthesized in a lab in 1912 and used in therapeutic settings throughout the ’70s and early ’80s before being labeled a Schedule 1 drug in 1985; and psilocybin, added to Schedule 1 in 1971. Psilocybin is found naturally in some mushrooms and has been used in Indigenous cultures all over the globe; mushroom iconography has been found in prehistoric cave paintings.

In the late 1990s, a handful of researchers started to take up the work that had been dropped when these substances were criminalized. (Dropped, at least, in aboveground situations; therapists continued, and still continue, working underground.) Now the field has exploded: When George says that “lives depend” on therapists learning to use these modalities, she’s not being dramatic. The numbers would impress anyone. In the Johns Hopkins smoking-cessation study, conducted in 2006 with a small group of participants, 80 percent of long-term smokers stopped smoking for at least six months after their psilocybin treatment. After a year, 67 percent were still nonsmokers. Nine years later, Johns Hopkins published the results of another trial in which psilocybin was used successfully to treat depression and anxiety in cancer patients, with the changes lasting in 80 percent of participants after six months. The university has invested so much in the field that it launched a stand-alone Center for Psychedelic and Consciousness Research last year and is working on studies to use psilocybin to treat addiction, anorexia and many other issues.

Meanwhile, in 2017 the FDA granted “breakthrough therapy” status to MDMA-assisted psychotherapy to treat PTSD, after privately funded MAPS studies found that 56 percent of participants experienced significant relief — so much so that they no longer met the requirements for PTSD. (The FDA can’t discuss ongoing trials, a spokesperson told me over email.) Breakthrough status is given to therapies that have shown great promise, with the idea that they will be given priority within the FDA approval process, and MAPS predicts MDMA-assisted psychotherapy will be available sometime in the next few years. I’ve experienced the treatment myself: After editing a story about MDMA-assisted psychotherapy many years ago, I connected with a highly skilled underground therapist to address the lingering effects of my father’s death when I was 14, effects that talk therapy and meditation hadn’t relieved. While it was difficult and painful to face the trauma that I’d buried, I greatly benefited from the work.

But as study after study showed positive outcomes over the years, one thing was constant: There was little diversity among both the study leads and the participants. In 2015, Natalie Ginsberg, MAPS’s director of policy and advocacy, came across the name of Monnica Williams, a clinical psychologist then at the University of Louisville. Williams, who is Black, studied obsessive-compulsive disorder, anxiety and the effects of racism, and her work excited Ginsberg, who wrote Williams to ask if she might be interested in working with MAPS. “Social marginalization compounds trauma,” Ginsberg wrote me via email. Regardless of the origin of their trauma, which could stem from any number of causes, including sexual assault, childhood trauma and military service, “people who experience the highest rates of trauma are those most marginalized from society, which in the U.S. includes people of color.”

Williams had no previous experience with psychedelics. “I had a boyfriend in high school who used LSD once or twice, and I don’t remember any remarkable transformations happening as a result,” she told me. It took some convincing. “It kind of seemed like maybe the fad of the week, you know?” recalls Williams. “Where they say, you know, you drink a glass of water with vinegar and lemon juice and you lose 50 pounds. Like, yeah, right. But actually reading the research, seeing the videos of the participants getting better ... when you do this work, you can look at people and you can tell: That person is really ill. And then you see that same person later and they’re smiling and their face is bright. And they’re making eye contact and they’re talking about the future. Seeing that whole progression on a videotape, that’s kind of what convinced me.”

In 2016, MAPS invited Williams to join its clinical trials to study MDMA for PTSD, but her trial would be unique: It would include only participants of color and mostly therapists of color. There was no reason to believe that MDMA would not work as well with people of color, but there was so little data that MAPS and Williams had no way to tell.

Jamilah George researched anxiety and racial trauma, and came aboard the study after meeting Williams at a conference. George was initially wary. “I’ve always seen drugs as dangerous, leading to violence and incarcerations,” George told me. “Never something that I saw as a means to healing, certainly not for exploration or fun. Learning more about psychedelics was strange for me: I was around all White people, talking about their experiences with these substances and how they’d changed their lives and how much they’d learned about themselves. It was so foreign to me and really difficult to wrap my mind around. A world in which you can use an illegal substance and aren’t at risk for being arrested? It was like, Where am I?”

The team spent two years preparing, using the guidelines set out by MAPS. First they went through their own training, including an MDMA-assisted therapy session of their own, called MT-1, so they could relate to and understand their participants’ experiences. They also had to find the right lab space at the University of Connecticut. Since MDMA alters consciousness, rendering participants more open and vulnerable — a state that allows for safe exploration, and then reprocessing, of trauma — the protocol requires them to spend the night after a treatment, which adds more regulatory issues and staff hours.

Trying to put the treatment into words — how does it work, exactly? — is a challenge, since psychedelic experiences are often ineffable, and people will respond differently depending on their unique circumstances, their brain chemistry and the setting in which the experience takes place. A note of caution, however: The research about psychedelic-assisted psychotherapy stems from therapeutic settings, where clients are carefully supervised, with adherence to protocols around usage and dosage — not a recreational one where multiple variables could be at play, like the purity of the substance and the surrounding environment. The few scientific voices expressing concern focus not on the research, but on the quick expansion of the field as a whole and the lack of research in nonmedical settings. “If these drugs are approved as therapeutic treatments, will pharmacological-grade drugs become easily available and used and abused recreationally?” asked Washington University psychiatry professor Eugene Rubin in a 2018 Psychology Today article.

To describe the treatment, MAPS therapists will often use the analogy of the body, says Sara Reed, a therapist in and study coordinator of the U-Conn. trial. “The MAPS language of the treatment approach is that there’s an intelligence that our body has, that wants to move towards healing,” says Reed, who is Black. “When you get a cut on your arm, as long as you are in a pretty healthy, functioning body, your body’s going to know what to do to heal itself, to stop the bleeding and create the scab. We believe that the psyche also has that same property. The psyche wants to move towards healing, but sometimes there are barriers that get in the way of that healing process. Our philosophy in this treatment is to create a container where some of those barriers are removed, so folks can process traumas in their own way, at their own time.”

The therapy “helps you look at the bigger picture,” says Terence Ching, a doctoral student in clinical psychology at U-Conn. and a therapist in the trial, who is Singaporean Chinese. “It almost feels like your life before was just zooming in on the puzzle pieces. Now you’re taking a step back — a few steps back — to see how things fit in. ... I can easily see how, for a person with PTSD who hasn’t responded to talk therapy, cognitive behavioral therapy or even medical marijuana, that this might be the thing that they might need to push things along so it clicks. And they can begin to enjoy their lives again.”

Despite the researchers’ optimism after their own experiences with MDMA-assisted psychotherapy, they soon faced obstacles. Williams quickly realized that the MAPS protocol for how to recruit participants, and then how to take them through treatment, was not going to work. “We were basically trying to take a study that had already been designed for White people and make it work for people of color,” she says. “The therapy has to make sense and feel like a good fit for the person getting it. And what may feel like good therapy for a White person may not necessarily resonate with somebody from a different ethnic group.”

This discrepancy showed up in recruitment. It seemed almost impossible to find participants. “The other clinics had long waiting lists of people trying to get into the study,” George says. “Our waiting list was empty.” The team realized they’d need to make some small but highly significant changes, like making sure they used the words “participant” and “study” in their materials, instead of “subject” and “experiment.” “We’re pretty aware of the history of medical atrocities committed against communities of color in the United States,” Ching told me. “We really wanted the language, at least, to reflect that we’re aware of that. We want to be more inviting, because there’s already that layer of stigma and mistrust of the medical system that communities of color have.”

Education during the recruitment period was different, too. “People of color needed more support in the screening process,” Reed says, to combat the cultural stigma associated with seeking mental health help, as well as fears that using psychedelics, even in a clinical setting, might lead to a harmful outcome. “What are psychedelics? What is MDMA? Am I coming here to get high? Could you tell me about what the overnight session is going to be like? Am I going to be safe? So we had to spend a lot of time educating participants and providing the language throughout the screening process, from informed consent to enrollment.”

“ ‘I would be your therapist,’ ” George recalls telling potential participants. “ ‘Me, a Black woman. The other person in the room will be a person of color. There’s a whole team committed to make you feel safe.’ Then you have to make them feel safe enough to want to hear more, then provide education about what the drug actually is. You have to get them to want to do the study.”

Once participants did enroll, the team had to tweak MAPS’s protocol further. MAPS was on board, George says: “Like, ‘Hey, we hadn’t thought about any of these things, and thank you.’ ” During MDMA-assisted psychotherapy sessions, participants listen to music through headphones — often relaxing, instrumental pieces that you might hear in a spa or a yoga center. The U-Conn. team wanted to curate these playlists to allow for music that would match each participant’s cultural background and intersecting identities.

The physical space also allowed for more cultural representation. “The paintings on the wall, the magazine on the table, the coffee mug we had — we were just really intentional that anything that our participants would come in contact with would only further their feeling of safety and that they belong,” says George. “We wanted folks to come in and say, ‘This is familiar. I recognize this artwork. I see people who look like me.’ We were explicit about cultural representation in our individual presentation as well. Maybe I’d wear a kente cloth head wrap. Making sure that we ourselves represented our own culture as a means to model that behavior for our participants so they can be fully themselves and let all their pain come forth — which is really difficult to do in a new space with new people, especially if you’ve never talked about that pain before.”

“What may feel like good therapy for a White person may not necessarily resonate with somebody from a different ethnic group,” says Monnica Williams, a clinical psychologist leading the trial.

Each enrolled participant was a small victory, a product of hours of psychoeducation. Reed says MAPS wondered why things were different with their team. “They would ask questions like, ‘You are spending a lot of time with your participants. What’s this about?’ It wasn’t like, ‘You need to stop,’ but it was just more of a curiosity. ‘What’s the difference in need at the site as opposed to other sites?’ The difference was that people of color needed more support during the onset of the screening process and this treatment, so we could actually retain them. There were some participants who, if there weren’t active engagements with them during this introductory process, the participants got overwhelmed and would leave or withdraw from the study prematurely.”

Time was another issue. The current protocol for MDMA-assisted psychotherapy includes 42 hours of therapy over 12 weeks. This includes multiple sessions with therapists before the actual dose of MDMA. Then, there are three dosing sessions spaced a month or so apart, and each dosing session lasts a full day (MDMA’s most intense effects last around four to six hours) with an overnight stay. In between, participants are supposed to see therapists regularly to explore what came up in the dosing sessions, with a series of sessions after the final dose. Some of the potential participants in the U-Conn. trial, however, found this time commitment to be insurmountable. The team wondered: Could they combine appointments? “We were trying to accommodate, but it was really impossible for a lot of people to commit to it,” says George. The obstacles continued: Potential participants had trouble convincing their families and partners that the treatment was worthwhile and safe. “[MDMA] is not a form of treatment that we’d typically experience,” says George. “It’s too foreign and scary for people.”

After two years of work, one participant made it all the way through: a client working with Sara Reed. The participant had “endured many experiences of trauma from his childhood, race-related trauma, trauma where his body was violated,” says Reed. “He carried so much in his body. In his first dosing session, [my co-therapist and I] saw his body relax in profound ways. He was laughing in such a way that I absolutely believe it was part of the release. He kept saying, ‘I feel so relaxed,’ and [my co-therapist and I] were looking at each other, witnessing his process of being able to relax for the first time in a long time — or ever, as an adult in this body, with all of its histories and complexities and memories. For him to be human: He wasn’t a person of color, he wasn’t a person who had traumatic experiences; he was someone who got to be human. It reminded me of my own experience of MT-1, where I felt freedom for the first time in my body. Of course we need more research to back this up, but I’ve found that people are able to experience some sense of freedom in their body with this medicine. To me, that’s something that has been part of my mission in this work — to help more people of color to be human, to relax. When presented in the right container, that is the power and the potential of this medicine.”

But after losing the prescribing psychiatrist on her team — the only member legally able to prescribe MDMA — Williams was forced to shut down the clinical trial altogether. It was a crushing disappointment, but also not surprising considering the obstacles they faced. “I think it’s more symbolic in a lot of ways,” Williams says of their research. Even if they’d successfully completed treatment for the 10 participants they’d originally planned for, it still wouldn’t have been enough data to say for certain how MDMA-assisted psychotherapy works with people of color vs. their White counterparts. “I think the bigger value is the amount of attention that this effort has gotten within the psychedelic research community," Williams says. “And how that’s been able to bring more changes, much more than we could have gotten out of the study itself.”

The training conference in Kentucky was a direct result of their partially completed study: The obstacles and the systemic issues pointed out by Williams and her team got the attention of MAPS and, crucially, its donors. (Donors to MAPS, a 501(c)(3) organization, span the political spectrum and include Dr. Bronner’s soap company, author Tim Ferriss and the Mercer Family Foundation; the Kentucky workshop was funded by the Open Society Foundations, Libra Foundation and the RiverStyx Foundation, among others.) “If you want this [treatment] to be accessible to people of color, you can’t use the same strategies that marginalized them in the first place,” says George. Marcela Ot’alora, a Boulder, Colo.-based psychotherapist who has been involved in MAPS’s MDMA work since the organization’s inception, helped lead the therapy training in Kentucky. “There are so many places where marginalized communities have to put up with going to a practitioner that is White and is not going to treat them the same way, or is not going to understand, and is going to maybe do things that are harmful in some way without knowing it,” she says.

Even with a new focus on inclusivity within psychedelic-assisted psychotherapy research, questions remain around issues of access. If and when the FDA approves MDMA used for PTSD, it will not be widely available; it will be an option only for people with a formal clinical diagnosis of PTSD. It will also be incredibly expensive: Estimates range from $13,000 to $15,000 per treatment round, and it’s not clear what might be covered by health insurance. The cost is not about the substance; it’s the therapeutic hours that will be required — the 42 hours of therapy, including three overnights — and the fact that therapists work in teams of two, a measure taken for patient safety. Clinicians are trying to figure out how to bring that immense cost down. Fewer appointments? Can the work be done in a group, so multiple clients can work together at the same time? (This is often how entheogens are used in traditional and Indigenous settings.) A sliding scale? Pro bono?

As lengthy as the process to FDA approval has been, there’s still a lot on the line for clinicians and activists. They want to see these treatments available, but they want to get them right. To this end, MAPS is launching a health equity initiative this fall to benefit marginalized clients, including therapist and supervisor scholarships and patient access funds. “It’s important to really slow down and really think about what — if we move towards mainstreaming psychedelics using psychotherapy — what implications does this have,” says Reed. “Is this going to be an elusive form of medicine, where there’s going to be a select few who have the luxury to take the time off to get the treatment, or who have the funds to purchase the treatment? Or are we going to make it accessible to some of the most vulnerable populations that need it: people of color, Black folks, trans folks, trans women of color particularly? ... Who are we really targeting in psychedelic medicine? That’s a huge question.”

 
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Psychedelic medicine is coming. The Law isn’t ready.

by Matt Lamkin | Scientific American | 31 Jul 2019

A surprising resurgence of psychedelic research has produced its first FDA-approved treatment, with more likely on the way.

In March, the U.S. Food and Drug Administration approved esketamine, a drug that produces psychedelic effects, to treat depression—the first psychedelic ever to clear that bar. Meanwhile the FDA has granted "breakthrough therapy" status—a designation that enables fast-tracked research—to study MDMA (also called "ecstasy") as a treatment for post-traumatic stress disorder and psilocybin as a treatment for major depression.

While these and other psychedelic drugs show promise as treatments for specific illnesses, FDA approval means doctors could also prescribe them for other, "off-label" purposes—including enhancing the quality of life of people who do not suffer from any disorder. Hence if MDMA gains approval as a treatment for PTSD, psychiatrists could prescribe the drug for very different purposes. Indeed, before the federal government banned MDMA, therapists reported striking success in using MDMA to improve the quality of intimate relationships. Recent research bolsters these claims, finding that the drug enhances emotional empathy, increases feelings of closeness, and promotes thoughtfulness and contemplativeness.‌

Similarly, while psilocybin has shown potential as a treatment for depression and anxiety, physicians could also prescribe the drug to promote the well-being of healthy individuals. When researchers at Johns Hopkins gave psilocybin to healthy participants with no history of hallucinogen use, nearly eighty percent reported that their experiences "increased their current sense of personal well-being or life satisfaction 'moderately' or 'very much'"—effects that persisted for more than a year.‌

Yet while the FDA generally does not regulate physicians' prescribing practices, a federal law called the Controlled Substances Act bars them from writing prescriptions without a "legitimate medical purpose." Although this prohibition aims to prevent doctors from acting as drug traffickers, the law does not explain which purposes qualify as "legitimate," nor how to distinguish valid prescriptions from those that merely enable patients' illicit drug abuse.‌

Would prescribing a psychedelic drug simply to promote empathy or increase "life satisfaction" fall within the scope of legitimate medicine—or would these practices render the physician a drug dealer?

To many the answer may seem obvious: to qualify as a "medical" use, a drug must be prescribed to treat an illness. But in fact, medical practice has always included interventions aimed at promoting the well-being of healthy individuals. Doctors provide contraceptives and induce abortions regardless of whether their patients' health is threatened by pregnancy. Plastic surgeons first honed their skills treating the traumas of the First World War, but quickly found themselves reshaping normal bodies and faces simply to enhance appearance.

Today physicians may prescribe stimulants to improve performance at school or minor tranquilizers to help cope with the ordinary stresses of modern life, regardless of whether patients meet the diagnostic criteria of a specific disorder. Indeed, some diagnoses themselves seem little more than thinly-veiled excuses to prescribe drugs simply to enhance quality of life—as when the FDA approved flibanserin to treat a condition called "hypoactive sexual desire disorder," which consists of not desiring sex as much as one would prefer.

At a time when "lifestyle drugs" are marketed as consumer products, it is increasingly difficult to draw a bright line that distinguishes legitimate medical practices from their illicit cousins. If prescribing mind-altering drugs to help healthy people achieve desirable mental states falls within the bounds of legitimate medicine, what is left of the concept of recreational use?

These line-drawing challenges argue for moving away from the drug war's simplistic, punitive approach in favor of more sophisticated strategies for minimizing the risks of psychotropic drugs. For example, when the FDA determines that a drug poses special risks, the agency can require Risk Evaluation and Mitigation Strategies, or "REMS," to promote the safe use of the drug.‌

Rather than focusing on whether a drug is prescribed for a "legitimate medical purpose," REMS can require physicians to register with the FDA and receive special training in order to prescribe the drug. Risk management plans can also stipulate that physicians may only dispense the drug in specific healthcare settings and that a healthcare professional must monitor each patient using the drug.

Similar strategies could be used to mitigate any unique risks posed by psychedelics, without limiting their use to patients suffering from particular disorders. One can imagine a system in which psychedelic drugs could be lawfully prescribed to a healthy individual, but only as part of a guided therapy session led by a specially trained physician. Multiple studies have found that both MDMA and psilocybin can be safely administered in well-supervised clinical settings like these, without harming patients or promoting drug dependence.

The prospect of psychedelic drugs gaining approval as treatments will force a reckoning for our existing system of drug control. While current policies characterize any use of these substances as illicit abuse, acknowledging that these drugs may offer meaningful benefits will require more flexible approaches. Psychedelic medicine may prove to be the thin end of a wedge that moves drug policy away from the elusive goal of eradication in favor of more nuanced strategies that harness the benefits of psychotropic drugs while minimizing their risks.

 
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Psychedelics, Therapy, and the Law - The risks and pitfalls of the emerging industry of psychedelic medicine​

by Psychedelic Frontier on Dec 8, 2020

The legal view of psychedelics is quickly heading for a change. A few organizations, like MAPS and Erowid, had maintained their position as providers of information during the illegal years. MAPS has focused on research, Erowid on information. They and others have held the fort, so to speak, but their effects have been small and, by themselves, they would not have precipitated social change.

Law and policy are not driven by science, they’re driven by expediency and advantage. In the US in the 1980s, psychotherapy was replaced by pharmaceuticals as subsidies for therapy were cut as part of a shift toward managed care. This was in spite of the success of therapeutic models and the lack of managed care alternatives.

Today’s interest in the potential of psychedelics are not solely due to breakthroughs in their use. That potential has been noted since the “Good Friday Experiment” of 1962, and there have been sixty years of positive reports since then. What’s different now is not the science, but institutional attitudes and social directions.

It appears that the promise of psychedelic-assisted psychotherapy is a leading force for this kind of change, but I suspect that this is more of a common cause and a rallying cry.

Psychotherapy, a new “white knight” on the scene, seems to be leading psychedelics in a drive toward legality but there is more going on. As prospective users, or as people who will be impacted by their use, it behooves us to look a little deeper into the alliances that are being formed. Let’s go back and look at some of the history.

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The Law

Scheduled drugs are a broad set of categories used to designate drugs purported to have no socially redeeming value. Schedule I includes heroin, LSD, MDMA, and peyote, which reflects little in the way these chemical are used or their risks. Schedule II drugs include cocaine, methamphetamine, and fentanyl, drugs that are harming more people but less punishable than the schedule I drugs. These categories were ill-advised and hypocritical from the start.

Amphetamines were used by all armed forces since WWII. The Axis forces, from those in the field to the High Command, subsisted on continuous drug abuse. US forces—all Allied forces I presume—also used amphetamines widely. In 2003, Dr. Pete Demitry, an Air Force physician and a pilot, stated that the use of speed was “is a life-and-death issue for our military.”

What’s different now is not the science, but institutional attitudes and social directions.

If you’re sending people out to kill each other, then you might as well extract every last bit of energy from them. A similar argument would hold that providing relaxation justifies servicemen’s use of marijuana, as roughly half of servicemen in Vietnam smoked it. This argument might not apply to the military’s use of opiates, as ten to fifteen percent of US servicemen were addicted to heroin during the Vietnam war. Or maybe it does, if it kept them fighting. But stateside, marijuana was illegal.

Marijuana’s illegality was not based on health factors but appears to involve racism and economics. An unpopular increase in Mexican immigration brought the herb into the country in the early part of the century, and the hemp industry threatened the news and paper industry.

Waves of laws were passed controlling pot from the early 20s until the blanket illegalization in the 1970s. These laws were peddled under false pretenses and with stunning biological ignorance. They followed the general mandate of outlawing alternative recreational drugs that threatened the alcohol and tobacco industries. These laws were also aimed at weakening the power of those who used them.

In 1970, President Richard Nixon spearheaded the Comprehensive Drug Abuse Prevention and Control Act. In 1971, Nixon initiated the “War on Drugs,” whose main goal was not public safety but the consolidation of power. John Ehrlichman, Nixon’s Assistant for Domestic Affairs, made this clear in 1994, long after the fact, when he said,

The Nixon campaign in 1968, and the Nixon White House after that, had two enemies: the antiwar left and black people. You understand what I’m saying? We knew we couldn’t make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did.

Nixon referred to Timothy Leary as “the most dangerous man in the world.” One might say this was a case of the pot calling the kettle black were not the Nixon administration more dangerous by far. Closely correlated with Nixon’s drug war, the incarceration rate of black Americans went up tenfold. In 2008, the Washington Post reported that one in five black Americans would spend time behind bars due to drug laws.

Subsequent administrations continued Nixon’s well-documented racism and exceptionalism, funneling money to fascist governments in Latin and South America through selective management of the illegal drug trade. This continued in Panama until it was exposed when Nicaraguan Contras downed a CIA airplane. Then, finally, the CIA had to wash its hands of Panama.

The hypocritical War on Drugs continued through all administrations, and continues still. Mexico’s former defense minister was just arrested in Los Angeles, finally identified as the long-elusive Mexican drug kingpin “the Godfather.” He was Mexico’s top military official from 2012 to 2018.

The war on drugs has been a war to make money, further political goals, personal interests, and to control people’s minds. It was clearly okay to mess with people’s minds when it benefited our imperial objectives or furthered specific interests at home. And while I think Donald Trump is, himself, about as helpful as global warming, what he refers to as “the deep state” has clearly been up to its armpits in drug money.

The War on Drugs has been divisive since its inception. Its purpose and method has been to divide and conquer, but tides have changed. Now racism is less fashionable—though still popular—and new money is to be made. In 2008 and again in 2018, polling revealed seventy-five percent of Americans believed the War on Drugs was failing.

The pretense of the War on Drugs is falling apart. People with drug addiction were first framed as devils, then criminals, and then as mentally ill. Toxic street drugs are now synthetic. Pot is not only tame by comparison, but a profitable legal business, a source of huge tax revenues, and even therapeutic—it’s questionable how much that really matters, though it’s good for public relations.

Now comes the next beachhead: psychedelics. The forces carrying the standard are psychotherapists with entrepreneurs close behind. Given how much graft, evil, and bullshit has been perpetrated so far, just how warmly should we welcome these new initiatives?

Are we trading illegality for medical restrictions in a situation where psychedelics should be legal for all? The inclination of the medical industry is not clear but, in the past, these organizations have struggled for the right to control medication.

I’ve spoken to leaders who recognize both the risk and the potential for moving restrictive powers from one authority to another. The general view is that this is an opening. The hope is that as the population becomes more experienced, they will become more accepting.

The general population has been clueless about the undercurrents of drug policy. How well-informed are these psychologists and entrepreneurs regarding the truth of the fray they’re entering? We may be enthusiastic to join enlightened psychologists in removing old restrictions, but what new rules are we working toward?


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Three sadhus, Indian spiritual ascetics who use cannabis to connect to the divine.

Therapy

The American Psychiatric Association, the APA, publishes the Diagnostic and Statistical Manual, the DSM, which is considered the final dictionary of mental disease and dysfunctions. It’s updated every decade or so and is now on its fifth version, last updated in 2012. The manual is written by committee or rather by many committees. Its contents and decisions are not scientifically validated, they are designed to meet current social standards and economic needs. The DSM serves many purposes as it is used as the basis for medical services, legal decisions, political programs, and individual diagnoses.

The APA serves three audiences. They serve the needs of their members which includes psychiatrists, psychologists, social workers, and their own management. They serve the public and public institutions which include your insurance company, courts, and legislatures. And they serve patients and clients of mental health services. Because this mandate and these services are so broad, you will not be surprised that there’s always a lot of discussion about every element of the DSM, from its general structure to its individual diagnoses.

Most users of the DSM think it was written just for them. Health service providers largely believe that the ailments described are real things that truly exist in people, for which they need therapy and from which they seek a cure. Clients involved in the legal system believe mental competence is well defined through reference to the DSM though, if pressed, attorneys will quickly admit that it’s what succeeds in court that counts, not what works at home. Hospitals and insurance companies are even less concerned with arguing the fine points. For them, the DSM is a structure they can build upon, and the truth is measured by their bottom line.

It is in this context that you must understand that the DSM is not written to meet any of these needs. It is written to provide a language for description and discussion of major social trends and dominant personal conditions. Its descriptions are not diagnoses in the usual medical terms, but rather behaviors and presentations that more or less define collections of people. There is no pretense of identifying disease or cure. The DSM really is a dictionary, a description of ideas, not an explanation or a proof of anything.

Psychedelics

When it’s said that psychedelics are being used for psychotherapy, what is meant is that psychedelics are being used to move people from one category of the DSM to another. You may think that what is meant is that your trauma, dependence, or depression might be cured, but cure is not part of the DSM. What is meant is that your presentation will be shifted such that you no longer fit the category. That is to say, it’s not what you think that counts, it’s what the doctors think, and it’s always this way when you surrender yourself to experts.

In these turbulent times, great cures are heralded as coming out of the jungle and from new studies. New cures are trumpeted for illness and addiction, and new means for revelation and personal growth. But as other ailments have shown, and as your insurance company will attest, it’s the people who set policy who will determine how these resources are made available. If we leave the power for change in the hands of the psychological and medical establishment, then it will be case in the terms currently established by the DSM. Mind expansion, revelation, insight, universal consciousness, and divine connection are not categories in the DSM.

If you want to benefit from mental health services then you’re going to need to present yourself as someone with a recognized dysfunction. If you want to be treated with psychedelics, then you’re going to need to have a diagnosis. Right now, as trials and experiments are being done, the criteria are lax. You can be included in a trial based on whatever the experimenters decide. But once treatments are established, you’ll need to fit within the paradigm.

It’s not clear how narrow or carefully controlled these parameters will be. Currently, Canada is moving to legalize psilocybin for terminal patients. That might mean you need to qualify for hospice, and this is probably something you’d rather not be qualified for.

We may be enthusiastic to join enlightened psychologists in removing old restrictions, but what new rules are we working toward?

MDMA is being tested in a therapeutic context for various forms of distress and dysfunction, but that’s not what most Ecstasy users are using it for. Should you need to be sick or dying before you’re allowed to use psychedelics?

The history of drug legalization spans everything from the eminently reasonable to the totally corrupt. Poisons should be regulated, and all medicines are poisons. Yet most poisons are not regulated.

You can make a fatal brew from the Foxglove you’ll find in almost every garden. Sales of Drain-o are not regulated and it will kill you quick. Sales of alcohol are regulated, but you’d be hard pressed to take a fatal dose. You can buy as much ethyl alcohol as you want if you pay the government tax, but you can’t buy any if you don’t. Ether is now considered toxic and you need a chemical permit to buy it, but it used to be freely available and people made it into cocktails. Who gets to say what poisons are legal?

Psychedelics are illegal out of medical ignorance and for political advantage, and remain illegal for those reasons. Accepting their use for psychotherapy proposes a laudable medical use, but does not address the enduring issues of ignorance and manipulation.

We would like to think that this is a step in the right direction, but where do these steps lead? Are we surrendering control to a more trusted authority?

We’ve been trained to trust our doctors. I’m a doctor—a doctor of physics—and a therapist, and I know better than to trust doctors and therapists. I don’t trust them in physics and I don’t trust them in medicine. Doctors and therapists are trained as practitioners within their scope of practice. Psychedelics are outside their scope of practice. There is little chance that revelation will fit within this scope. How would you feel if your personal growth required your doctor’s approval?

If these new initiatives lead to more exploitation and control for profit and politics, then we should not be so enthusiastic. Psychedelics hold more promise than returning things to normal, and I object to the limited view that psychedelics should only serve psychotherapy.

If what we want is intelligence, insight, and autonomy, then we should remain attentive to the full promise of personal growth for the reform of individuals, society, and ecology. Psychedelics are not toxic medicinals, they have the potential to be consciousness expanding entheogens. This is a far larger goal that assisting psychotherapy. We must keep these larger personal and social goals in our sights.


 
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The struggle to turn psychedelics into life-changing treatments

by Nicola Davison | WIRED | 12 May 2018

Scientist Robin Carhart-Harris wants to use psychedelic drugs to treat psychiatric disorders. Early results are promising – but can he convince big pharma and the public of their potential?

In late 2016, Robin Carhart-Harris had a morbid IDEA. The head of psychedelic research at Imperial College London and his lab were about to embark on a study of dimethyltryptamine (DMT). The compound is more commonly ingested in the form of ayahuasca, a psychoactive brew boiled from the Banisteriopsis caapi vine and Psychotria viridis, or chacruna, leaves. It has been used for centuries by indigenous cultures in Latin America to communicate with the spirit world and, more recently, by millennials on voyages of self-discovery. People who take ayahuasca report of mental journeys to other realms. Many have visits from unearthly entities. Experiences like these are also described by those who come close to death. So Carhart-Harris set out to discover whether psychedelics in general, but especially DMT, induce a state in the brain that is similar to the act of dying.

I meet Carhart-Harris at his office in Hammersmith, west London. Out of the window, muddy playing fields stretch beneath a midwinter sky. The conversation is suitably gloomy but, in a way, it is typical of the research fellow, who can be pensive and grandiose.

Scanning the brain of a volunteer who is tripping on DMT is not a simple procedure, Carhart-Harris tells me. Electroencephalogram (EEG) caps are full of sensors that are disturbed by the slightest movement.

Participants are blindfolded. A minute or so after the drug is injected, they begin to hallucinate vivid geometric patterns that bloom in texture and scale. Every minute, the researchers ask the participants to rate the intensity of their experience from nought to ten. In Carhart-Harris’s previous studies of LSD and psilocybin, the psychoactive compound found in magic mushrooms, the peak would be around seven.

“For volunteers, there seems to be some kind of threshold at which there’s almost a pop,” – he snaps his fingers – “into this DMT world.” On the EEG monitor the researchers can see when the threshold had been crossed. The peaks and troughs of the oscillating traces of the reading usually become shallow, indicating that a lot was happening.

While under the influence of DMT, participants do not always hear the researcher’s questions. “I was in this place that was unbelievably bright and full of unconditional love,” one subject tells me. “And when I was coming back to my body it was more blue, purple and dark. Then I saw this being, this insect-like being that was female, and she opened her arms and then her tongue came out of her mouth and she entered me.”

It takes participants about 15 minutes to fully return to their normal selves. Afterwards, they are asked to describe their experience using a questionnaire: Did you feel separated from your physical body? Did you feel a sense of harmony with the Universe? Of course, the ratings were subjective, one of the limits of psychology. Yet when the answers were tallied and compared to those of people who had been through a near-death experience, there was little statistical difference.

Carhart-Harris was not surprised with the results. He has long suspected that psychedelics induce some kind of mind death that mimics an aspect of the death process itself. He felt that the measure was useful because it revealed something about the nature of the drugs in their ability to give users a new way of thinking. Similarly, people who have had a near-death experience will say that they are able to see the world afresh.

For half a century, researchers interested in psychedelic drugs have inhabited the fringes of neuroscience. In the UK, Carhart-Harris is responsible for making this field of study respectable again. He has spent much of the past decade investigating the ways certain compounds give rise to uncommon conscious states. He thinks that Lysergic acid diethylamide (LSD), psilocybin and DMT are powerful tools for accessing the brain. “The term ‘psychedelics’ comes from Greek words for ‘mind-revealing’ – and that’s what these drugs do,” Carhart-Harris says.

“The question is, what is dying? I guess a major part of the death process is that the thing at the top of the hierarchy, if you like, that tends to dominate consciousness ordinarily when you’re awake, is the first thing to go. That’s why DMT is useful. You can appeal to the lessons that are there when you understand that your ego isn’t absolute. That’s an amazing insight, and it can be a really healthy insight. It can allow you put things in perspective.”

He also believes that psychedelics could potentially be used for treating mental illness. Current treatments for depression, anxiety and addiction can be life-saving, but they also have limits. About a third of people treated for depression never fully recover.

In England, antidepressant prescriptions have doubled in the last decade: one in every 11 UK adults is prescribed them. Psychedelics, Carhart-Harris thinks, could be used to deliver a turbo-charged form of therapy, one that does everything that psychoanalysis does, but in a more cost-effective manner.

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Patients are given capsules containing psilocybin, a naturally occurring psychedelic.

Robin carhart-Harris is not the first scientist to think that psychedelic drugs could be used to treat psychiatric disorders. Albert Hofmann, the Swiss chemist who first synthesised LSD in 1938, referred to his discovery as “medicine for the soul”. In the 50s and 60s, tens of thousands of patients were given psychedelics for disorders such as anxiety and addiction. A 2016 meta-analysis of 19 studies published between 1949 and 1972 found that 79 percent of patients showed “clinically judged improvement” after treatment. But the heyday would be short-lived: in 1971, LSD was made illegal thanks to the United Nation’s Convention on Psychotropic Substances treaty, ending all major research programmes.

Carhart-Harris, who is 37, entered the field just as the disapprobation of drugs was waning. In 2006, a study by Francisco Moreno at the University of Arizona, Tucson, found that psilocybin reduced the symptoms of obsessive-compulsive disorder in nine patients. Then, in 2011, another study found that the same alkaloid significantly eased the anxiety of people dying of cancer. Each year, there are progressively more clinical trials with psychedelics. In 2016, three investigated the therapeutic action of psilocybin; another looked at ayahuasca.

Brain imaging has also transformed neuroscience. The development of functional magnetic resonance imaging (fMRI) means it’s now possible to observe the brain thinking, doing and feeling. Scientists in the 60s “second wave” of psychedelic research – the first being the use in indigenous cultures – could only guess at the biological mechanisms by which the drugs change the brain. Carhart-Harris uses imaging to unpack their mysterious power.

The offices of the Psychedelic Research Group are on the fifth floor of Imperial’s Burlington Danes building. There, on Thursdays, Carhart-Harris holds a team meeting. On the day I attend, he has just returned from Peru where he had been invited to carry out a brain scan on a participant in a traditional shaman-led ayahuasca ceremony.

In person, Carhart-Harris is polite and warm. He is medium height and athletic, with just-greying hair and electric-blue eyes. His humour runs on the dry side. “I’ve just come back from a retreat in the Amazon,” he tells the group. “It’s now very clear to me that the spirits are real and science is a waste of time.”

In his office is a framed poster, bought at the Sigmund Freud Museum in Vienna, containing the quote: “It is not easy to deal scientifically with feelings.” On shelves above his desk, behind a bottle of mouthwash and a disposable razor, are Freud’s complete psychological works. “I have something quite frightening,” he says, reaching for an A3 pad on the top shelf. Text copied from Freud’s books, referenced and colour-coded, filled every sheet. On a page entitled “The Ego”, one phrase – “WITH THIS IDENTITY IS ATTAINED” – is capitalised and highlighted.

Carhart-Harris has a reputation in the department for excessive indexing. “At one point he asked if I could borrow a book from the library for him,” David Erritzoe, a psychiatrist and research fellow, tells me. “I said, ‘OK, but why can’t you go yourself?’ He was like: ‘It’s a bit problematic.’” Carhart-Harris had been banned for highlighting and scribbling in the library’s books. The ban remains in place today.

As a scientist, Carhart-Harris has two overarching and interlacing concerns: he wants to understand how psychedelic drugs act on the brain in order to so dramatically alter thought, mood and behaviour; and he wants to see if their power can be harnessed to serve humankind.

A few years ago, he undertook a study to see if psilocybin could be used to treat depression. He enlisted 20 people who had tried at least two courses of medication, so called treatment-resistant depressives. On average they had lived with the disorder for 17.7 years. On dosing day, each patient would arrive at Imperial at 9am. After answering a questionnaire in the patient lounge and taking a urine test, they were led to a room that had been decorated to look more like a bedroom than a clinic, with drapes, flowers, music playing and electric lights that flickered like candles. After swallowing the psilocybin capsule, the patients were invited to stretch out on a bed. Two psychiatrists stayed in the room – Carhart-Harris believes that a soothing environment and psychological support before, during and after dosage is essential. People on psychedelics are psychically vulnerable; anxiety and paranoia are not uncommon.

When the results came in, they showed that the depression had reduced in all of the patients. (The results reflect the experiences of 19 people; one dropped out.) Three weeks after dosage, nine were in remission; after five weeks, all but one felt less depressed.

Carhart-Harris admits the study has its problems: it was not placebo-controlled and because of the small sample size it is not possible to make grand inferences. Yet for some of the participants, the treatment was life changing. “Before, I was like a beetle on its back, now I am on my feet again,” reported one. Another went out for dinner with his wife for the first time in six years, feeling “like a couple of teenagers.”

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In the UK, Carhart-Harris is responsible for making the study of
psychedelic drugs in neuroscience respectable again.


The second of three brothers, Carhart-Harris was born near Durham in northeast England. When he was four, his family moved to Poole on the south coast. He was raised Catholic, and though he is now an atheist, traces of the altar boy remain. Psychedelics, he says, were suppressed during the 60s like a “forbidden fruit” of which knowledge was too dangerous.

In his youth, Carhart-Harris was not academic. He liked PE and science, but would hide his school reports. “I remember one that started, ‘Robin’s behaviour gives cause for concern as he progresses into his GCSE years’,” he says. “I was a bit of a precocious raver.” He was also hobbled by anxiety. Once, when asked to read aloud to his classmates, he found he couldn’t breathe. He went to the University of Kent to study biochemistry but dropped out. He returned home and applied to his local university to study psychology. “I wrote this personal statement – you know what young people are like sometimes, grand and over the top – I was saying how I wanted to help people to just live and not be shackled by mental-health problems.”

Carhart-Harris first encountered Freud in 2004, during his masters at Brunel University London. At a seminar on “methods to access the unconscious mind”, he discovered that Freud’s theories rest on a belief that the mind is like an iceberg, with the majority of its mass hidden from the view of the conscious self, which he called the “ego.” He was captivated by Freud’s ideas but saw that there was no empirical evidence to support them. “I thought, what is this cult if all it is is us believing?” Born in an age before computers and brain imaging, Freud had relied on blips in the system, be it slips of the tongue, compulsive patterns of behaviour or dreams. Carhart-Harris was amazed that these were still the methods espoused by his professor. Dream interpretation just seemed too kooky.

Back in his room, he typed “LSD unconscious mind” into the library search engine. It returned a title from 1975, “Realms of the Human Unconscious: Observations from LSD Research” by Stanislav Grof. He took out the book and read it that same day. Something clicked: “I was like: this is fucking big. You can prove something really fundamental about the mind.”

Freud had said that dreaming was the “royal road” to the unconscious. Carhart-Harris felt sure the same was true of psychedelics. He began to wonder: how is the ego represented in the brain? What are the neural correlates? He felt that the obvious place to start was with a scan of someone’s brain on LSD. He looked for a lab where such a thing might be possible.

Carhart-Harris wrote to David Nutt, then the head of the psychopharmacology unit at Bristol University. (Nutt has since moved to Imperial.) Nutt was interested in brain circuitry and addiction and was publicly critical of drugs policy; in 2007 he lost his place on the Advisory Council on the Misuse of Drugs, a body that advises the government, over outspoken remarks. He agreed to meet.

“I went along, nervous as hell,” Carhart-Harris said. “I told him ‘I want to study the brain on LSD, I think it could tell us a lot about Freudian principles and their biology.’” Nutt heard him out, but rejected his proposal. Then he asked if Carhart-Harris was interested in MDMA. The department was in need of a PhD student to investigate whether the drug damages the brain’s serotonin systems. Carhart-Harris said that he was interested but left feeling despondent. On the way home he called his mother. She advised him to accept the offer, that it could act as a stepping stone.

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An MRI scanner in Carhart-Harris’s laboratory at Imperial College London.

The study of neurons to try to understand how consciousness arises is a waste of time, says Carhart-Harris. All experiences – from the disgust of seeing a dead rat to the memory of a childhood holiday – happen as diverse parts of the brain become networked. In an fMRI scan, electromagnets detect changes to blood flow in the brain. Since neural activity increases blood flow, it is possible to observe discrete parts of the brain reacting to various stimuli; on screen, engorged regions are presented as colourful splotches. Zoom in too closely and the full picture is lost. “It’s not thinking about the quarks or atoms in the neurons,” Carhart-Harris said. “That’s kind of meaningless, there are too many steps and levels to get up to a point at which you have a functioning system that maps on to something that you can feel.”

Normally the brain is good at hiding its vast and unfathomably complex machinations. Most mental activity is not under conscious control, and we only notice the fact if we make a Freudian slip or pause to consider a pupil dilating. One barrier between the self and the vast data-processing thought-swamp of the rest of the brain is what neuroscientists call the “default-mode network”. It is an intricate system of interlinking brain regions that together give rise to what some call the “monkey mind” – the stream of internal chatter that surfaces in between periods of more focused thought.

By studying LSD, Carhart-Harris has found that psychedelics do something unusual to the default-mode network. In a 2016 study published in the Proceedings of the National Academy of Sciences journal, he injected 20 healthy volunteers with either 75 micrograms of LSD or saline, a placebo, on two separate occasions. As the drugs kicked in, volunteers reported a “sense of eerie dread” as their anchorage in the world shifted. “Usually, depending on how it goes, there’s a bit of a kick back, there’s some anxiety.” They then had two fMRI scans followed by a magnetoencephalography (MEG) scan – if the various scans pointed to the same mechanisms the results would be stronger. Afterwards, volunteers responded to a questionnaire so that scan data could be correlated with experience. Statements included “sounds influenced things I saw” and “edges appeared warped.”

In the brains of the volunteers, as the visual network became more connected (all the LSD-injesting participants hallucinated), the blood flow in the default-mode network receded, indicating that it had lost its force. For the participants, this correlated with a change in the way they processed the world. The monkey mind had gone quiet.

In society we talk approvingly of “well-rounded” individuals and “getting ourselves together”. But a little chaos can be a good thing. In certain psychiatric disorders, the brain becomes entrenched in pattern. Someone with depression might have relentlessly negative thoughts about themselves; people with obessive-compulsive disorder get trapped in repetitive action.

Carhart-Harris believes that psychedelics work like a reset button. He likes the analogy of shaking a snow globe. Under LSD, as the default-mode network disbanded, other segregated parts of the volunteers’ brains began communicating in an unpredictable way – a state of increased entropy. Psychedelics seem to break down entrenched ways of thinking by dismantling the patterns of activity on which they rest.

For instance, the most-prescribed class of antidepressants, selective serotonin reuptake inhibitors (SSRIs), raise levels of serotonin in the brain by blocking its natural reabsorption. When we are anxious or stressed, parts of the brain become overactive. Serotonin, a neurotransmitter, binds to receptors in the brain that are prevalent in regions involved in stress and emotion, the 5-HT1A receptors. Once bound to the receptor, serotonin initiates a signal that decreases the activity of the neurons. By keeping the 5-HT1A receptors doused in serotonin for longer than normal, SSRIs calm the stress circuitry. But they also blunt emotion more generally.

Psychedelics work on the brain rather differently. Though they also temper serotonin, they target the 5-HT2A receptors, concentrated in the cortex. Humans have vastly more cortex than other species, and the 2A receptors are dense in regions with human-specific traits such as introspection, reflection, mental time travel and the self itself.

Carhart-Harris thinks that when psychedelics disrupt the level of connectedness in the cortex they create space for insight and catharsis. For patients, the process can be difficult. “You need to be able to say to people: this could be tough, it could at times be the worst experience of your life and you may see your worst fears staring at you in the face.” But he believes that the process can be freeing. “I think it’s possible to know your defences and know your insecurities and through knowing them not be at the mercy of their force.”

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In July 2017, Carhart-Harris gave a talk at a conference called Breaking Convention, which bills itself as “the largest psychedelic conference in the known Universe”. Held at the University of Greenwich, the gathering was good-natured, with a propensity for tie-dye. The programme listed 150 speakers from across the psychedelics spectrum. One talk was on the nascent field of phenomenoconnectomics, a largely theoretical method of quantifying altered states. Another was titled “Encounter with the Jaguar.”

Carhart-Harris stuck around for most of the conference, fielding entreaties from undergraduates, hobnobbing and catching a few science talks. He attended a lecture called “Mental Organs and the Depth and Breadth of Consciousness” by Thomas Ray, a biologist at the University of Oklahoma. As talks on consciousness go, it was difficult to follow, whipping through molecular compounds, the evolutionary tiers of the mind and the “rise of insanity.” When Ray presented his central idea, that “conscious space” is modulated by the brain’s 5-HT7 receptors, Carhart-Harris sat forward. “These are wild extrapolations,” he whispered.

In the question-and-answer session, Carhart-Harris’s hand shot up. “Have you plotted the correlation between the affinity of psychedelics for the 5-HT7 receptor and the drug’s potency?” Ray said that he had not. “I think that you should, it’s important.” People fidgeted: this was not a hostile crowd.

Afterwards, Carhart-Harris left the conference and stopped in a local café for lunch. He was quiet, almost ruminative. “How can you present such poor science? I think that people should be allowed to speculate. But the people who contribute to the mainstream perception that this research is pseudo-scientific undermine the field.”

The episode had tapped into something deeper. Research with drugs that are strictly controlled by the law is not straightforward. In the UK, LSD is a class A, schedule 1 drug. Heroin, which causes more harm to individuals and society than LSD, and is addictive, is in the slightly less prohibitive schedule 2 because it is a diamorphine, which can be used for medication. For a lab to stock LSD it must acquire a licence from the Home Office and meet certain criteria, such as having a fridge that is bolted to the wall. All this is demoralising. It took Carhart-Harris three years to execute the psilocybin-depression pilot.

Funding is also an issue. Big pharmaceutical firms are generally not inclined to back research into drugs that are illegal and un-patentable. Carhart-Harris’s studies have been largely financed by grants, donations and crowdfunding. In 2016, he applied to the Wellcome Trust, the largest charitable supporter of science in the UK. When he was shortlisted, he thought he stood a chance. He had meticulously designed the two trials he was hoping to carry out if he got the £1 million-plus grant. But one of the judges on the panel took issue with his suggestion that “well-being” should be a primary outcome. Carhart-Harris had the impression that the judge considered it flowery. He didn’t get the grant.

“I’ve got a feeling they’re always thinking: he’s a hippie,” he tells me at lunch. “And when something comes out of your mouth like: ‘I want to measure well-being’, they are like: I knew it! He’s a hippie, he’s not a real scientist.” Carhart-Harris went back to the trust, asking them to be honest: was it the area he was researching? But when they said it wasn’t, he didn’t believe them.

Later that evening, at the conference soirée, Carhart-Harris gets talking to the organisers of a Finland-based conference on psychedelics at which he is scheduled to speak. What, they want to know, does he think of ketamine? A study at the University of Oxford has found that some patients with treatment-resistant depression responded positively to the drug. Carhart-Harris tells them that the work is interesting, but he does not think ketamine is as important as psilocybin.

Of all the psychedelic drugs, Carhart-Harris believes that psilocybin is probably the closest to becoming legal. It has fewer stigmas attached to it, and in the brain, LSD is active for far longer, making it less practical in the clinic, while DMT is probably too powerful. The fact that psilocybin occurs naturally in mushrooms also helps. It could be marketed as a natural alternative to antidepressants. He believes that, one day, psychedelic therapy will be available on the NHS, just like SSRIs and cognitive behavioural therapy are today.

This spring, he plans to do another psilocybin study, this time directly pitching psychedelics against SSRIs. Fifty people living with depression will receive either daily doses of escitalopram, an antidepressant, or a single 25mg shot of psilocybin, plus therapy. The contest is unequal, in one sense, because those taking escitalopram will have a regular reminder that they are taking medication. “Maybe psilocybin will work at least as well, that’s my prediction,” Carhart-Harris says. “But imagine that psilocybin is more effective? That’s really quite…” he tails off. “That would be something.”

 
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Taking Psychedelics Seriously

Ira Byock, MD, FAAHPM

Recently published studies in peer-reviewed journals and high-profile articles in the New Yorker, New York Times, and Wall Street Journal, have rekindled professional and public interest in the therapeutic use of psychedelic drugs. It is easy to understand the enthusiasm. The magazine and newspaper articles include accounts of patients with profound depression, demoralization associated with terminal illness, and anxiety related to post-traumatic stress disorder (PTSD), who experienced remarkable improvements, including some who had previously considered suicide.

Nevertheless, psychiatric and palliative care clinicians who care for profoundly depressed, anxious, and seriously ill patients have every reason to be skeptical. As people become more mentally or physically ill and established treatments remain insufficiently effective, patients' susceptibility increases. Physicians play an important role in protecting vulnerable patients from spurious, nonevidence-based miracle cures, as well as from scientifically grounded, but overly zealous burdensome treatments that are certain to do more harm than good.

An abundance of caution should be accorded psychedelics, which carry real risks and are formally designated Schedule I drugs, signifying that they are dangerous, without therapeutic value, and illegal. Older clinicians remember news stories of deaths of individuals high on hallucinogens who thought they could fly, those with bad trips and flashbacks, and studies that purported to show chromosome damage associated with use of LSD.

However, given the extent of persistent emotional and existential suffering that palliative care clinicians encounter in the patients we serve, these medications deserve serious consideration by our field.

Background

Psychedelic properties of mushrooms and cactuses have been used for centuries by indigenous cultures to induce expanded states of consciousness and spiritual experiences. During the 1950s and early 1960s, research sponsored by the National Institute of Mental Health demonstrated potential for drugs of this class to markedly alleviate depression and existential suffering among people with cancer.11–13 Subsequently, non-medical use of these drugs and associated political and cultural upheavals resulted in the Schedule I classification, abruptly banning psychedelics from further clinical research and medical use. Although many of the mid-twentieth century clinical trials involved people with terminal conditions, few references to these published studies can be found in the literature of palliative medicine, a young specialty that developed after this period. Over the past 20 years, a few small clinical studies were conducted abroad, mostly in Europe and the United Kingdom. In the United States, over the past decade, with support from the Multidisciplinary Association for Psychedelic Studies and private funders, a few tenacious researchers earned governmental permission to carry out carefully designed trials of pharmaco-assisted therapy with psilocybin and MDMA.

The recently published research strengthens findings of earlier studies, showing significant efficacy and few adverse effects when these medications are administered as adjuncts to psychotherapy to carefully screened patients, under medical supervision. Three drugs, psilocybin, ketamine, and MDMA, have attracted most of the recent attention. Psilocybin, a naturally occurring drug found in psilocybe mushrooms, has strong and durable benefits for some patients with treatment-resistant depression, and for those with demoralization, anxiety, and depression associated with terminal illness. Ketamine, a Federal Drug Administration (FDA)-approved anesthetic with analgesic and psychedelic properties, has been used off-label in patients with treatment-resistant depression. In case studies and small clinical series, ketamine has shown notably positive effects. MDMA, a drug synthesized in 1912 as a potential anticoagulant, was later found to have strong psychoactive properties. In the 1970s and early 1980s, psychiatrists who administered MDMA in the context of psychotherapy observed sometimes dramatic improvements in patients suffering from severe, treatment-resistant PTSD.

In deciding how to think about these drugs, the distinction between skepticism and cynicism bears examining. Skepticism is warranted, but cynical nonscientific bias can result in therapeutic nihilism. The history of medicine is studded with occasional leaps in progress—consider small pox vaccination, penicillin, and computed tomography scans—that, shortly before they occurred, might have seemed too good to be true. When I graduated from medical school, the idea that duodenal ulcers were caused by bacteria would have been risible; stem cell transplants and gene-editing therapies were the stuff of science fiction. Surprising medical advances humbly remind us to suspend cynicism and that honest inquiry is warranted.

The need is great

While not only for people who are dying, specialty palliative care teams serve the sickest patients in our health systems and communities. It is, therefore, not surprising that we occasionally encounter incurably ill people whose suffering persists despite all available evidence-based treatments.

In treating pain and other physical distress, established treatment protocols guide escalations of doses and combinations of analgesics and co-analgesic medications. When a patient is dying and physical pain, dyspnea, seizures, or agitated delirium persists and causes intolerable suffering, as a last resort, comfort can reliably be achieved with proportionate sedation.

However, not all suffering is based solely in physical distress. Palliative care clinicians and teams also encounter patients whose misery is rooted in emotional, social, existential, or spiritual distress. Cancer, heart failure, liver failure, and amyotrophic lateral sclerosis (ALS) or motor neuron disease are among the diseases that can result in a progression of personal losses: Of feeling in control. Of taking care of one's self. Of contributing to others. Of enjoyment. Of meaning and purpose. Ultimately, some ill people say they have lost any reason to go on living.

People who are incurably ill and living with progressive disease-related disabilities can experience anxiety, depression, and demoralization. Psychotherapy alone and drug treatments for such syndromes are often insufficient. Medications for depression may take weeks to become effective or prove ineffective. Antidepressants and anxiolytics carry side effects that can include mental slowing and confusion. These adverse effects are particularly common and hazardous in patients with advanced physical illness, who are also at risk of polypharmacy, multidrug interactions, and concomitant disequilibrium and falls. When nonphysical suffering persists despite prudent approaches, published, evidence-based guidelines are limited.

Severe psychological and existential suffering can rob people of feeling that life is worth living. A sense of unending helplessness and hopelessness compels some to consider ending their lives. Suicide rates have risen 24% over the past two decades and are highest among middle-aged and elderly adults, particularly men who may suffer most from feelings of dependency. Public health data from Oregon show that since implementation of the Death with Dignity Act, the large majority of patients who received prescriptions for lethal drugs were motivated by nonphysical suffering. Current or fear of future pain contributed in just 26% of cases, while loss of autonomy, decreased ability to enjoy life, and loss of dignity most often brought these people to contemplate hastening their deaths.

Exercising an abundance of caution: screening, supervision, set and setting

Prescribed to carefully screened patients, in recommended doses, in the context of professional counseling and supervision, psilocybin and MDMA have proven to be notably safe. They have no tissue toxicity, do not interfere with liver function, have scant drug–drug interactions, and carry no long-term physical effects.

These drugs are not intoxicants in the usual sense. They do not dull the senses or induce sleepiness. On the contrary, sensory perception is intensified and attention is aroused. Although abuse syndromes have been reported, few people become habituated to these drugs.

Adverse physiological effects are few and of short duration, but can be substantial. During the onset of psychedelic experiences nausea and vomiting are not unusual. In this first hour or more, visual and spatial orientation are commonly disrupted, which can give rise to anxiety. Sympathetic nervous system arousal may occur both because of fear, and from direct effects of the drugs. Particularly during the initial phase of sessions, psychedelics dissolve barriers between physical senses resulting in synesthesia; touches, smells, and tastes can take on sounds, shapes and colors. Similarly, emotions and thoughts may evoke visual images and sounds. These phenomena explain why the term hallucinogen is often used synonymously with psychedelics to refer to this class of drugs.

Clinicians and researchers familiar with this class of pharmaceuticals emphasize the importance of screening, supervision, and “set and setting.”

Screening

Not every suffering patient is a candidate for therapy involving psychedelic drugs. As a general guideline, people who have cognitive and emotional conditions associated with disorganized or diminished ego strength are not good candidates for pharmaco-assisted therapy with psychedelics. MDMA may represent a partial exception to this exclusion, because it has fewer cognitive and sensory effects and more salutary emotional and interpersonal properties. Contraindications include people with borderline personality disorders or schizophrenic tendencies.

Supervision

Supervision is necessary for ensuring safety of psychedelic experiences. Short-term psychological effects are profound. If used in unsupervised fashion by unselected and unprepared people, these drugs can be highly dangerous and, in extreme cases, cause death. The sensory effects described above interfere with hand-eye coordination and fine motor function, making operating a vehicle or machinery or even walking in public potentially dangerous. These effects are sufficient to emphasize that professionals who are skilled in managing adverse effects must be present. Most research into pharmaco-assisted therapy with psychedelics has by protocol required subjects to remain in a single comfortable room throughout the sessions. In addition to safety, the supervising therapists are able to guide patients through their experiences to optimize the drug's beneficial potential.

Set and setting

Anthropologists studying traditional use of psychedelics by shamans and indigenous people recognized the influence of expectations and motivation on subjective experience. Since the earliest psychological research into pharmaco-assisted therapy with psychedelics, clinicians have emphasized the importance of “set and setting.”

The dissolution of assumptions and diminution of barriers caused by these drugs extend to psychological and interpersonal realms of experience. An enhanced sense of connection to others not only underpins some of the therapeutic effects, but also results in vulnerability to emotional contagion. When taken without adequate preparation and when surroundings are anxiety-provoking—either physically uncomfortable or emotionally intimidating—the psychedelic experience predictably results in fear, a prolonged sense of dread, or full panic. Conversely, in controlled settings with elements of soft light, art, and appropriate music, or nature, and gentle, compassionate people, such adverse reactions are rare.

With adequate counseling and preparation, and when psychedelic experiences unfold in calm, aesthetically pleasing environments, they prove beneficial in a high proportion of cases. In these situations, the healing motivations of both therapists and patients may contribute to therapeutic outcomes.

Therapeutic effects

Clinical case studies and research trials describe common patterns of subjective experiences that are associated with therapeutic benefits for people with severe anxiety and depression. As the initial phase of psychedelic experience wanes and people regain familiar barriers between visual, auditory, tactile, olfactory senses, people typically report heightened cognitive clarity and expanded emotional receptivity. Previously unrecognized or unquestioned assumptions related to one's place in the world and relationships to nature, one's physical and social environments become available to being considered anew.

While psychedelic experiences vary significantly from one individual to another, research subjects and people interviewed for journalistic articles commonly express attributes, which include heightened clarity and confidence about their personal values and priorities, and a renewed or enhanced recognition of intrinsic meaning and value of life. People often voice a sense of exhilaration, insight, and strengthened connection to others, as well as a richer sense of relationship with nature or God. People who take psychedelics with an intention of spiritual introspection often report that the drugs opened windows into deeper realms of existential experience. In safe and supportive environments, these effects typically induce a state of wonder, conceptual frame shift, expanded capacity for love, and an intensified sense of connection. Patients living with medical conditions that had robbed them of hope or reason to live may experience a transformative shift in perspective and experience of inherent meaning, value, and worth.

Not all psychedelics drugs are alike and subcategories have been described. Drugs, such as psilocybin and LSD, classified as entheogens, are associated with introspection and new insights, shifts of perspective, and reframing of experience and relationship to others and the world. MDMA is characterized as an empathogen, referring to prominent emotional effects of interpersonal warmth, empathy, and openness. These properties may underlie the benefits of MDMA in the context of therapy for those suffering from severe PTSD.

For most of these drugs, a single six to eight-hour session or short series of sessions suffices for therapeutic benefit. Alleviation of anxiety and depression may persist for weeks to months and, for some, proves permanent. Exceptions to this treatment pattern include protocols of daily low-dose ketamine for depression and recent nonmedical reports of daily or every third day microdosing of LSD.

Political and regulatory considerations

Psychedelic drugs were closely associated with the cultural wars of the 1960s and 1970s when strong political undercurrents contributed to this class of drugs being classified Schedule I. Similarly, MDMA became well known as Ecstasy or Molly, a popular, illicit rave and party drug. In the mid-1980s, despite evidence of MDMA's striking efficacy and relative safety when used therapeutically, the FDA declared MDMA a Schedule I agent. Court rulings challenged that classification; however, in 1998 the FDA reaffirmed and made the Schedule I classification permanent.

The process of renewing clinical research of psychedelics has been long and painstaking. Future efforts to reclassify selected psychedelics, such as psilocybin, as Schedule II drugs, enabling both research and clinical administration will likely meet predictable political resistance. There are compelling reasons, however, to address the expected concerns of opponents and proceed with efforts to reclassify these drugs.

Treatment-resistant depression and anxiety associated with PTSD causes untold suffering and contributes to thousands of deaths each year. A few population health studies suggest that rising suicide rates may in part be due to suicide becoming less shameful and more socially acceptable, lowering barriers for people who feel hopeless. A person with severe depression, who has a coexisting serious, life-threatening physical condition, may feel that his or her quality of life is not worth living and may forgo arduous, but potentially life-saving treatments. Additionally, nearly one sixth of Americans live in states where physician-hastened death is legal and those with terminal illness may choose this option in absence of alternative sources of relief.

There may be higher ground on which political conservatives and progressives—as well as those on opposing sides of the issue of legalizing physician-hastened death—might build consensus. Given the life-threatening nature of persistent, treatment-resistant depression and PTSD, including among veterans of America's wars, and the rising incidence of suicide, the reclassification of psilocybin and MDMA can be legitimately cast as a right-to-try issue. Right-to-try legislation has been used to provide terminally ill patients access to potentially life-extending medications that have been tested in Phase I trials but are of uncertain benefit. Similarly, the FDA's expanded access or compassionate use provisions may make use of drugs that have not been approved available to patients who are otherwise facing death. By diminishing a desire to die among people with severe depression, anxiety, PTSD, and those with terminal cancers, genetic and neurodegenerative diseases, psychedelics may have greater life-saving effects than other drugs that have earned right-to-try and expanded access status.

Final thoughts

Faced with novel therapies with reported clinical benefits that seem too good to be true, skepticism is warranted to protect vulnerable patients from harm. Cynicism, however, may prove more dangerous still. Unscientific bias and nihilistic assumptions can keep effective treatments from people who desperately need them.

Despite the controversial history of psychedelic medications, palliative specialists who care for patients with serious medical conditions and common, difficult-to-treat nonphysical suffering have a duty to explore these hopeful, potentially life-preserving treatments. Against the backdrop of physician-hastened death becoming legal in five states, expanded research of clinical psychedelics must proceed.

In reexamining the use of psychedelics in pharmaco-assisted therapy, we must not allow preconceptions, politics, or puritanism to prevent suffering people, who are now considered helpless and hopeless, from receiving promising, at times life-saving, treatments.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867510/
 
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Sgt. Pepper

Why doctors are turning to psychedelics to treat depression, addiction

by Julia Savacool | Men's Journal | Dec 20 1019

For decades, mental health experts have amassed anecdotal evidence that psychedelics could help people with intractable diseases like addiction, depression and PTSD. Scientists at the Johns Hopkins Center for Psychedelic and Consciousness Research in Baltimore, which opened in the fall, plan to test these drugs rigorously so that one day they could be prescribed. We talked with two of the center’s founding members, Alan Davis and Albert Garcia-Romeu, who are seeking out mental health and addiction treatments, to find out more about their research and how they plan to change our lives.

A lot of your focus is on psilocybin—the psychedelic agent in magic mushrooms. How does it help people suffering from depression or addiction?

DAVIS: There are a couple of ways we believe it works. First is the experience itself. People who take psilocybin report having a deeply positive, mystical experience that seems to help them alter their perspective on their situation. More specifically, people with depression tend to feel isolated and disconnected from their daily lives. The experience of taking psilocybin makes them feel an intense interconnection that stays with them after the experience is over. People also report gaining insight on their depression, like they suddenly have an awareness of what they want to change in their life to help them move forward. That awareness, coupled with this mystical-like experience, serves as the catalyst for change.

ALBERT GARCIA-ROMEU: It helps people change their perspective, which is really useful for someone who is depressed or dealing with addiction. On the physical side, psilocybin disrupts patterns in the brain—patterns of negative thinking that become entrenched over time.

How does it do that?

GARCIA-ROMEU: In a nutshell, psilocybin and other psychedelics like LSD bind to serotonin 2A receptors, creating mood-altering effects and changes in brain function. We know psilocybin decreases amygdala blood flow in people with depression, which is associated with better antidepressant effects. This is important because depressive symptoms seem to be associated with over-reactivity in the amygdala. Keep in mind that the data for psilocybin brain mechanisms in depression is very limited, from fewer than 20 people total. We are only starting to scratch the surface of how this works.

When people hear psychedelics, they picture mushrooms growing in the back of their college roommate’s closet—not the stuff of scientific rigor.

GARCIA-ROMEU: Honestly, it’s closer to a dorm room than a science lab. Our study setting looks like a therapist’s office: sofa, chairs, soft lighting. The most clinical item is a blood pressure monitor, which we use to keep track of physiological measures at 30- to 60-minute intervals throughout the sessions. One of the strongest predictors of a challenging experience or “bad trip” can be an overly cold and clinical setting, so we do our best to make it a place that feels warm and safe. Volunteers usually spend around eight hours here before any drug is administered, with the two people who monitor them after they’ve taken the drug.

Where do you get the drugs?

DAVIS: The psilocybin is made for us by an academic chemist and put into a capsule that’s taken orally. This isn’t microdosing. A dose is moderate to high—more than recreational doses in a festival environment, for example.

How are the results looking?

DAVIS: We just wrapped up the main portion of the depression study, and now we’re doing follow-ups and preparing the data for publication. We had 24 participants—all studies here are done on people, not animals. Preliminary findings show approximately half of the participants had complete remission of depression at one month after the intervention of psilocybin plus psychotherapy, which is very promising.

When will potential treatments be available to the public?

DAVIS: We expect the full study to be published this coming year. After that, it can take several years before the treatments are approved by the FDA and made available to the public.

What has been the biggest challenge you’ve encountered in your research?

DAVIS: Funding. The government hasn’t been backing this kind of work. So to get $17 million in private money [donors include entrepreneur Tim Ferriss, WordPress co-founder Matt Mullenweg, and the Steven & Alexandra Cohen Foundation]—that goes a long way to getting the quality of studies we need to move the therapeutic research forward.

A psychedelic experience lasts a few hours, but depression can haunt a person for years. How can a single dose of psilocybin have such a lasting effect?

DAVIS: A couple of days after use, the person experiences a halo effect. Their mood improves, and they may be more open to suggestion. We use that time to help them make lifestyle changes to alter their outlook. It’s not like the person just takes psilocybin, and that’s it. We still use a full therapy approach, and we’re optimistic this may lead to greatly improved outcomes in people who have not found success in traditional treatment in the past.

So it’s 10 years from now, and psilocybin has been approved for medical use. How will it work, practically speaking? Will a person get a prescription for psilocybin?

GARCIA-ROMEU: That is probably one of the greatest misconceptions around this work. This is not a take-two-and-call-me-in-the-morning type of treatment. Nor is this like cannabis dispensaries where patients pick up the medication and take it at home, unsupervised. Psychedelics have the potential for much more intense and unpredictable psychoactive effects, so it’s best to administer them under carefully controlled conditions, in conjunction with intensive psychological support. Probably the best parallel in current medical care would be getting general anesthesia before surgery—this only happens at a medical facility under the careful supervision of a specially trained doctor and support staff.

Even so, this sounds life-changing for some people.

DAVIS: Absolutely. We see a future where we can actually heal these problems instead of simply trying to reduce symptoms. Our results point to a potential neurological and psychological basis from which we can understand this healing potential, and that could revolutionize our understanding of what “treatment” actually means. No longer would we be trying to help people get by, but they might actually heal and then thrive.

 
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Ayahuasca: A possible cure for Alcoholism and Depression

by Pablo Noguiera | VICE | 25 Dec 2015

Brazil is at the forefront of research into ayahuasca as a therapeutic drug.

Jorge* is around 60 years old, works a white collar job, has gray hair, married children, and grown grandchildren. People who work with him would never imagine that he participates in religious rituals using a mind altering tea.

And yet, thanks to ayahuasca, Jorge became a teetotaler. A big change for someone who, when he was younger, would buy several cases of whiskey at once. "I opened the boxes and started emptying the bottles in the kitchen sink. My wife was shocked," he told me.

He's not the only alcoholic to renounce booze after an experience with the mystical drink. In 2010, after a decade of failed treatments, Robert Rhatigan took a trip to the Peruvian Amazon, where he participated in four rituals conducted by a shaman. During a speech at a TEDx event, he recounted how he "saw the several components from his mind floating in space, as if they were pieces of a puzzle" while under the effects of ayahuasca. The experience lasted two hours and included hymns sung by the shaman and severe purging sessions. By the end of the ceremony, he "saw" the pieces returning to his head. The one that corresponded to his alcohol addiction no longer fit in. There he knew that he was cured. "My transformation is something far from understood in Western medicine," he says.

There are some hospitals, universities, and research institutes in the West and around the world that are experimenting with powerful psychoactive substances, such as psilocybin, ibogaine and even LSD are being analyzed in hospitals and research institutes all around the world.
"Regarding ayahuasca studies, Brazil is at the forefront of research."
"Regarding ayahuasca studies, Brazil is at the forefront of research," said Luis Fernando Tófoli, professor of the medical psychology and psychiatry department of Unicamp and coordinator of the Laboratory of Interdisciplinary Studies of psychoactive drugs, in Portuguese.

This year, a study conducted by Brazilian researchers was published in Nature. The piece examined the effects of the drink on two men and four women who showed symptoms of depression, ranging from moderate to severe. The participants consumed ayahuasca only once in doses that ranged between 120ml to 200ml prepared by a church of Santo Daime. They then had their mental health monitored through three questionnaires repeated eight times, the first one 40 minutes after intake and the last one three weeks later.

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The results showed that there were improvements shown by every participant, disregarding the levels of depression they displayed. According to one of the surveys, one day after the experiment, there had been a reduction of 62 percent in symptoms. One week later, the efficacy kept going up, getting up to 72 percent. According to another survey, depression symptoms such as sadness, difficulty concentrating, suicidal and negative thoughts, had been reduced by 82 percent. Side effects were not detected, although half of the subjects had vomited under influence of the tea.

The results impressed the researchers. "We observed antidepressant effects the first hours after administering ayahuasca, and they remained significant for two to three weeks," Flávia de Lima Osório and Rafael Guimarães dos Santos, two of the authors, said in an email in Portuguese. She's a lecturer in the department of neurosciences and behavioral sciences of the Universidade de São Paulo (USP) Medical School in Ribeirão Preto and he is a postdoctoral researcher in the same department. "Besides, ayahuasca was tolerated quite well by the patients. The majority described the experience as positive, even if there was vomiting and nausea."

The fast results could be good news for those who need quick-acting treatments. "Antidepressants that are currently available take weeks to produce therapeutic effects, in addition to having significant side effects, such as sexual dysfunction and weight gain," Flávia wrote. "Many patients don't get an effective therapeutic response. New pharmaceuticals, that act faster and more efficiently with less side effects, are necessary."

Tófoli agreed. "Antidepressants that were recently introduced to the market, do the same as the older ones. New substances able to act on other receptors, haven't been introduced yet. Psychopharmacology has not been able to get that type of response," he said.

The combination of being thirsty for good news with the thrill associated to mind altering performed in labs can help one understand the hype that followed the release of the research. After becoming news on Nature, the research was highlighted by some leading news channels around the world, from Huffington Post to Scientific American.

The news coverage made the researchers wary. Flávia requested to be interviewed only by email "because there were already issues with previous reports." She also reiterated that nothing is really demonstrated. "This is a pilot-study, with a few volunteers and without double-blind testing controlled by placebo. On studies with antidepressants in general, the placebo effect can be very significant. Therefore, we can't affirm yet that ayahuasca has antidepressant capabilities, let alone that it can cure depression," she wrote.

A new wave of ayahuasca enthusiasts may appear in the very near future. In Natal, the researcher Dráulio de Barros Araújo, from the Brain Institute of UFRN, coordinates a study using placebos to compare the effects of the tea in a group setting of 80 people, half of them diagnosed with depression. On top of receiving medical supervision, the subjects will be submitted to high definition electroencephalography (EEG) exams. "A study with this kind of consolidated methodology aiming to evaluate the potential benefits of ayahuasca for depression patients has never been done before" said Tófoli, one of the researchers. "If we find positive results, we have all we need to cause a certain impact."

Another study, published this year in the journal Physiology and Behaviour, analyzed the effects of ayahuasca on lab rats that were addicted to alcohol. The study was authored by Alexandre Justo de Oliveira-Lima, who is a pharmacology professor at State University of Santa Cruz; Eduardo Marinho, of the same university; and Laís Berro, of Federal University of São Paulo; along with researchers from Brás Cubas University and from the Institute of Forensic Science of São Paulo.

Research with animals is one step in the development of new drugs and, also, a resource for better understanding of organic alterations caused by the process of addition. The problematic of use of drugs, by both animals and by humans, is linked to the feedback loop between the ventral tegmental area (VTA) and nucleus accumbens, which theoretically make up our reward and pleasure system.

Oliveira-Lima already had experience with analyzing how drugs like anti-psychotics fight alcohol addiction. Stories about the possible benefits of ayahuasca caught his attention. "We decided to do this research because there's this ambivalence regarding what causes benefits, if it's the religious experience or the tea acting directly," Lima said in Portuguese.

During the study, rats were injected with ethyl alcohol to induce changes in cerebral activity and behavior. Their motor skills were then evaluated. Because low doses of alcohol have a stimulant power, the subjects tend to move through greater distances when they are under the influence.

There were two experimental phases. During the first phase, the animals were separated into groups. One group received doses of saline, which served as a control. Others received doses of ayahuasca with different concentration levels and, later, alcohol injections. "We are simulating a situation where a person goes to a ritual, takes the tea and then drinks alcohol," Lima said. One group received just alcohol injections, always with the same dose.

Ten days later, the researchers compared the frequency with which the animals moved. The results showed that those who received ayahuasca moved about 50 percent less than those who only had alcohol, suggesting that the tea desensitized the rats to alcohol. The tea appeared to prevent the changes in cerebral activity induced by alcohol, resulting in milder behavioral responses.
"We decided to do this research because there's this ambivalence regarding what causes benefits, if it's the religious experience or the tea acting directly."
In the second experiment, the animals were again split in several groups. One received saline injections only to serve as a control. The remainder of them were sensitized by alcohol, that is, they became dependent. Afterwards, ayahuasca injections were administered for eight consecutive days, in attempt to revert the sensitization. After seven days, new alcohol injections were given and movement frequencies between groups were compared. The graph showed that animals that were experiencing the effects of alcohol for the first time, as well as the ones submitted to the desensitization process with the tea earlier, displayed exactly the same behavior. In other words: the "dependency" was reverted.

It's as if an individual who was addicted to alcohol went to rehabilitation and got treated by being given ayahuasca for just a few months, Olivera-Lima said. "With sensitization reversal, that person would be less prone to feel like drinking again," he said. "And even if they relapsed, at first the experience would be milder."

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In theory, as we learn more about the neurochemistry of ayahuasca, we could engineer medications that wouldn't require patients to spend hours vomiting while hallucinating in a sweat lodge (by the way, it's worth to point out that the rats didn't vomit during the study).

"Nowadays there are few medical options that are effective enough for the treatment of alcoholism. From studies like these, pharmaceutical companies can become dedicated in developing new products. I believe that ayahuasca will be a big source for the treatment of addiction in the next decades," Lima said.

The next step for the researchers will be to repeat the process of sensitization and desensitization and then remove the brains from the rats to analyze the changes. Unfortunately, a recent budget cut for Brazil's National Program of Post-Graduation will likely impair these experiments. "Although scholarships have been preserved, those cuts affect up 75 percent of the budget that cover the necessary means for the research," Lima said. "One equipment line that was going to be purchased, for example, was cancelled for the year. That will reflect negatively on Brazilian science for the next five years."

One of the reasons Brazil has some of the most active research in ayahuasca is because back in the 80s, legislation was passed to permit religious use of the tea. "We are grateful for the religious groups because they gained rights and conditions that allow us now to do research," said Tófoli.

He emphasizes that studies have shown ayahuasca is not for everyone. "There are people who can have psychotic breakdowns," he said.

The ayahuasca debate still is far from resolution. There are many external factors that may play into the effectiveness of a medication. Getting a prescription involves so much more than just consuming a drug. That experience includes many seemingly irrelevant, but potentially important, sub-experiences. The patient is thinking, either subconsciously or consciously, about whatever negative stigma or positive association they have with the drug. They're having an experience with the psychiatrist, and another at the pharmacy. There may be effects of stress or emotion at any of these stages.
Studies have shown ayahuasca is not for everyone.
The same is true of ayahuasca, but such emotional impacts may be magnified because the drug is so mind-altering. This can introduce new ethical questions as well as uncertainties about what's actually causing the effects.

Recall the experience Robert Rhatigan had, where he cured his addiction after "seeing it" outside of his own mind. With ayahuasca, there seem to be more things involved than just neurochemistry.

"Many people decide to change things about their lives during the experience. There are those who decide to become vegetarians, for example," said Tófoli. "How would we talk about whether the benefits are caused by the chemistry or what a person experiences during the mind altering process? We can't be sure."

But wait. Didn't the experiment with the rats demonstrate that it is essentially a physiological matter, independent of what happens in the conscious mind of who is experimenting ayahuasca?

"And who says that the rats don't have a conscious mind?" Tófoli said.

A very psychedelic response. But it's a good reminder that we're still far from understanding the fundamentals of ayahuasca therapy.

 
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How medical science is grappling with psychedelic plants*

by Wesley Thoricatha | Psychedelic Times | 4 May 2020

In our continuing conversation with Professor David Nutt, we discuss the latest research efforts at Imperial College London where he is the Edmond J. Sapfra chair in Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences. We also touch on the challenges of using psychedelic plants such as ayahuasca and iboga in modern scientific research contexts.

Thank you again for speaking with us, Professor Nutt. What current research and frontiers are you exploring at Imperial College London?

Well, I’m very excited about three things. One is that we’ve just finished the first MDMA and alcoholism study—a safety, tolerability and feasibility study given to alcoholics to see if MDMA could help them overcome the traumas that lead them to drinking. We used exactly the MAPS protocol: 2 x 125mg doses 2 weeks apart. It was well-tolerated, considering these are often very physically sick people, and the MDMA didn’t show any unwanted effects. A significant number stopped drinking completely, so it was a very positive outcome—safe and effective, looking way better than conventional talk therapy. So we’re writing that up now.

Within the next few months we will have finished our head to head of psilocybin study, 2 x 25mg doses [three weeks apart] vs Escitalopram for depression. That’s going to be a very interesting study looking at clinical outcomes, side effects, and brain mechanisms. That will be out in probably August or September of this year.

We’re also just finishing analysis of our first DMT imaging study, which is I think the first fMRI study of DMT given intravenously. We’re looking forward to seeing those results, hopefully quite soon.

So those are three things we’re quite excited to happen this year. Coming up, we have a psilocybin OCD study and a psilocybin anorexia study, and hopefully a psilocybin for opiate addiction study which is one I’m particularly interested in—to see if psilocybin can help people free their brain from heroin dependence.

Interesting—when it comes to opiates, you hear mostly about iboga and ibogaine.

You do… The thing about ibogaine is it’s quite a difficult drug to use. It has way more cardiac effects than psilocybin. I don’t know whether we could use ibogaine in Britain because of its cardiac effects. But you know, there’s no theoretical reason why ibogaine should be better than psilocybin. Both have powerful ego-dissolving effects and people find them useful to help them stop using harmful drugs, but maybe psilocybin will be just as good. It’s something we can use here, whereas we can’t use ibogaine.

You sometimes hear about ayahuasca too, but it’s difficult for us as scientists to use ayahuasca because you can never be sure what’s in it. That’s one of the reasons we did the DMT imaging study—because DMT is DMT. They say the effects are too short to be properly therapeutic, but we are working on a slow infusion so you can potentially mimic the prolonged effects of ayahuasca. This could also avoid the complications of having to give plant products whose strength and authenticity can’t really be validated, and also without having to give harmaline (which in itself could have therapeutic actions as well; we don’t know.) Ayahuasca isn’t necessarily just a DMT product—it’s got a lot of harmaline, and harmaline is a monoamine oxidase B inhibitor, and that complicates interpretations of the findings because those are powerful drugs themselves.

When I spoke with Brad Adams a few years ago, he mentioned that a group in Spain found a way to freeze-dry and encapsulate ayahuasca preparations to make it easier to control strength and dosages.

Yes, but the reality is that ayahuasca will never be licensed as a medicine under the current regulations. In Europe, and with the FDA, they set such strict standards for replication of purity and concentration that I don’t see how it could be done. I mean, I suppose you could make a thousand liquid tons of it and freeze it, but that’s not going to be cheap.

You’d need an army of curanderos and curanderas blessing it and praying over it!

[Laughs] I mean, I wish things were different. I’d rather we loosened up our attitudes on these things. But the current approach we have towards pharmaceutical safety and marketing is so heavily biased in favor of huge pharma companies that can do the very expensive safety and replication studies, which are almost certainly not needed for drugs that have been in use for millenia by thousands of people. The model is wrong for plant products. But it’s going to be easier to get the products on the market than it is to change the model. That’s why we do our psilocybin studies—trying to bring something to people within the model, rather than break the mold. But I think at some point, the mold may well break.

Right, It’s an interesting dichotomy there. These ancient indigenous traditions and their healing methods simply aren’t compatible with our “scientific rigor.”

But isn’t it lovely that we are discovering people that knew more than we did? It’s very satisfying as a scientist to discover that all you’re doing is framing ancient knowledge in a new way, a more rigorous and pharmacological way, but the actual understandings are the same. The plants are the same, the effects are the same… you’re just giving them a different notation, a different explanation. But the content and the process is the same that it’s been for thousands of years, I find that really quite satisfying. There are very few areas of science where that is true. Maybe none.

Yes, isn’t it humbling? And in a sense, does the ayahuasca perhaps not want to be tamed and put into that paradigm? It’s almost saying, “You have to come to me and approach this with a different set of ideals and understandings in order to have this experience.”

I certainly think in terms of nonmedical insights, it’s definitely preferable to have a good shamanistic experience rather than just going to your doctor and getting a capsule.

*From the article here :
 
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Embracing Ecstasy

by Liza Gross | The Verge | May 22, 2019

On a chilly spring morning in 2017, Boris Heifets took the podium to talk about MDMA in an Oakland, California, hotel ballroom packed with scientists, therapists, patients, and activists. If he noticed the occasional whiffs of incense and patchouli oil coming from the halls of the Psychedelic Science meeting, he didn’t let on. After all, anyone studying the therapeutic benefits of the drug that sparked an underground dance revolution 30 years ago knows that ravers, Burners, and old hippies flock to this meeting. It’s the world’s largest gathering on psychoactive substances.

Ecstasy enthusiasts and university professors alike heard several research teams report that MDMA helped patients recover from post-traumatic stress disorder (PTSD) and other disabling psychiatric conditions after conventional treatments had failed. Meeting rooms buzzed with excited chatter about the prospect of MDMA getting approved as a prescription therapy for PTSD. That could come as early as 2021 if it proves safe and effective in large clinical studies that are just getting underway. For many advocates of this work, regulatory approval can’t arrive too soon.

But Heifets, a Stanford neuroanesthesiologist, had come to lay out an even grander role for the drug federal officials banned in 1985 in a futile effort to quash the burgeoning rave scene. Psychiatric treatments lag decades behind the rest of medicine, even though serious mental disorders carry just as much risk of disability and death as cardiovascular disease, Heifets explained. Psychiatrists desperately need more targeted therapies to give their patients the same kind of rapid, enduring relief that stents and bypass surgery provide for heart patients. He thought they’d benefit from thinking like surgeons. “I don’t want to suggest that we can cure psychiatric disease in 30 minutes in the operating room,” Heifets said. "But we can harness powerful drugs like MDMA that act like a surgeon’s knife to alter consciousness and exorcise psychological demons."

For many at the meeting and in the reemerging field of what some call psychedelic medicine, there’s no reason to look further than MDMA. A few hours after Heifets spoke, two therapists who used MDMA in sessions with 28 PTSD patients in Colorado reported that 19 participants no longer met the criteria for their diagnoses a year after treatment. "MDMA helps melt the walls people hide behind to protect themselves," said Marcela Ot’alora, the principal investigator of the study. "That allows patients to explore the coping strategies that have failed them for so long." Other teams reported encouraging results from small studies using MDMA to alleviate severe anxiety in adults with autism and in people confronting life-threatening illnesses.

"MDMA’s therapeutic power may come from strengthening the bond between therapist and patient by enhancing feelings of trust, emotional openness, and empathy," Heifets told the audience, pointing to the commentary he and his mentor, Robert Malenka, published in the journal Cell. To his surprise, a few therapists approached him after the talk to say they quote the paper to tell their patients that the world needs more empathy.

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There’s no question that MDMA is showing therapeutic promise and could potentially help a range of socially debilitating disorders, Heifets allows. But MDMA, an amphetamine derivative, can raise heart rate and blood pressure, which can prove dangerous for people with cardiac and vascular problems. Though ecstasy is almost never pure MDMA, recreational use can cause panic attacks. In rare cases, it can trigger psychosis in susceptible individuals, which is an unnerving experience ravers have shared on Reddit. Such risks, combined with its bad rap as a party drug, may limit its ability to help patients, Heifets cautions. He’s convinced that MDMA has an even greater potential to revolutionize psychiatric care by giving scientists clues about how to develop next-generation drugs. Ideally, those drugs would be more clearly targeted and have fewer risks than MDMA. Potentially, they could even treat more disorders.

If psychiatrists are ever going to catch up with the rest of medicine, they need a better understanding of how the brain works so they can guide it back to health when it breaks down. MDMA is the only psychoactive drug that enhances positive social interactions and empathy. Heifets believes this offers researchers a unique opportunity to probe the brain.

The same properties that make ecstasy-fueled ravers hug between dance grooves also make the drug uniquely suited to help scientists figure out how the brain supports social behaviors. Because its powerful effects don’t last long, researchers can model those behaviors in animals and link them to cellular networks in the brain. "Go to a rave, and you’ll find people glassy-eyed, staring inches from each other’s faces in rapt conversation," Heifets says. "What they’re saying doesn’t matter. The deep emotional connection they’re experiencing, however, does. That’s what we’re after. How can we bottle that?”

If scientists can capture that magic, he believes, they can sidestep the inherent difficulties of working with a demonized substance steeped in the trappings of a subculture that still inhabits the fringes of society. After the Colorado investigators described how they used MDMA in therapy, a woman in the audience complimented them on the power of their aura, which she said was violet blue and “pretty incredible.” After a brief pause, Ot’alora smiled and thanked the woman, who said she works in the Akashic Records, described by adherents as a sort of cosmic transcript of everything that has ever happened in the history of the world.

Talk of auras and Akashic Records comes with the territory at a meeting with “psychedelic” in the name, and most researchers take it in stride. They’re waiting to see if mainstream medicine will embrace MDMA, assuming the promising results from early PTSD studies hold up under the scrutiny of the larger clinical trials. But Heifets doesn’t want to take any chances that shifting political winds will once again shut down work with the still-popular club drug — along with any hope of ushering in a new era of psychiatry.

Heifets works in Malenka’s lab in one of the nation’s largest regenerative medicine facilities. The center was built a decade ago to foster groundbreaking therapies for some of medicine’s most intractable diseases. A massive Chihuly chandelier hangs just inside the center’s front entrance where the sculptor’s trademark glass tendrils evoke the networks of neurons that hold the secrets to health and disease. It’s just a short walk from the lab to the hospital where Heifets spends one day a week tending to brain surgery patients.

Heifets didn’t set out to study a controlled substance. “My mom told me I should never study psychedelics,” he says with an impish grin. “It’s a good way to kill a promising career.”

Still, MDMA piqued his interest even as an undergrad. So when he wandered into Malenka’s lab one day and heard him speaking with a colleague about a controlled substance application to do research with MDMA, he went “full in.”

Heifets was just seven years old in the summer of 1984 when the Drug Enforcement Administration proposed new rules to ban MDMA under Schedule I of the Controlled Substances Act, citing “illicit trafficking,” high abuse potential and “no legitimate medical use.” "By then, ecstasy had become so popular," Heifets says, "that you could buy it with a credit card over the counter at clubs in Texas."

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The allure of MDMA’s feel-good effects has captured the imagination of adventurers ever since a trailblazing cadre of psychotherapists started using it in the late 1970s. MDMA was discovered in 1912 by German chemists looking for drugs to stop bleeding. It was rediscovered in 1976 by chemist Alexander Shulgin. The legendary psychedelic chemist famously cataloged the effects of nearly 200 psychedelic compounds he’d made in his home lab. He reported feeling “pure euphoria” on MDMA, which he called his “low-calorie Martini” with the “special magic,” and shared the compound with psychotherapists he thought might find it of use.

Those therapists had seen more than a thousand MDMA-assisted breakthroughs with patients, with no major side effects, by the time the government moved to criminalize the drug. Many of them petitioned federal officials to keep it available for their patients. Philip Wolfson, a San Francisco-area psychiatrist who’d used MDMA in hundreds of therapy sessions, testified that the drug had helped patients in severe emotional distress with a poor prognosis. “I am extremely concerned that this promising new psychotherapeutic agent will be lost to the medical profession,” he said.

The government’s campaign to ban a drug with potential medical benefits caught the attention of the era’s king of daytime talk TV, Phil Donahue. In 1985, he devoted an entire show to MDMA. “It makes you love everybody,” Donahue said. “Now, who doesn’t want to take ecstasy?” Several people on the show explained how MDMA had helped them come to terms with life-threatening illnesses and heal fractured family relationships in therapy. Chicago addiction expert Charles Schuster, however, said he had “great concern” about MDMA because he and his colleagues had found that MDA, a chemical cousin, produced long-term brain damage in rats. “If MDA does this,” Schuster warned, “then I have reason to suspect that MDMA may as well.”

That was all DEA deputy assistant administrator Gene Haislip, who also condemned MDMA on Donahue’s show, needed to hear. A month after appearing on Donahue, Haislip announced an emergency ban on MDMA.

The DEA’s ban effectively shut down research on MDMA’s medical benefits, but it did nothing to stop the explosion of underground ecstasy-fueled parties where DJs prided themselves on spinning the most eclectic electronica. Filmmakers mined raves’ trance-inducing beats and light shows as the backdrop for thrillers, crime capers, documentaries, and love stories. Irvine Welsh of Trainspotting fame explored his fascination with “rolling” on ecstasy in a collection of “chemical romance” stories, one of which was eventually adapted for the big screen.

Meanwhile, Schuster was tapped to head the National Institute of Drug Abuse (NIDA), which showered scientists investigating MDMA’s toxicity with millions of federal dollars. It didn’t take long for the NIDA’s investment to pay off. In 2002, researchers led by George Ricaurte — a co-author on Schuster’s MDA study — reported in the prestigious journal Science that recreational doses of ecstasy could cause permanent brain damage in monkeys and possibly lead to Parkinson’s disease. Psychiatrists familiar with the drug questioned the plausibility of the $1.3 million study, which was funded partly by grants on methamphetamine toxicity. Politicians, meanwhile, cited the research to push the Illicit Drug Anti-Proliferation Act — originally introduced in 2002 by Sen. Joe Biden (D-DE) as the Reducing Americans’ Vulnerability to Ecstasy (RAVE) Act — to imprison and fine club owners and promoters for allowing MDMA on their property.

Five months after Congress passed its anti-rave legislation, Ricaurte reported that he’d mistakenly given his animals meth, not MDMA, and retracted the paper. The fiasco, described as an “almost laughable laboratory blunder,” got its own chapter in the book When Science Goes Wrong: Twelve Tales from the Dark Side of Discovery. But the damage had been done. Federal officials continued to bankroll their preoccupation with proving that MDMA causes brain damage while ignoring known risks along with its healing potential.

It took researchers almost 20 years after the ban to get federal permission to test MDMA as an experimental therapy. But federal agencies don’t fund clinical studies on the drug, forcing researchers to rely on nonprofit sources such as the Multidisciplinary Association for Psychedelic Studies (MAPS).

MAPS director Rick Doblin, who founded the organization in 1986, has been instrumental both in getting the Food and Drug Administration’s permission to test MDMA in people and in shepherding it through the drug approval process. Although MDMA could gain FDA approval for PTSD within two years, Doblin is working to make it available as soon as August under the agency’s expanded access program. "The program gives patients with severe or life-threatening illnesses access to experimental drugs when no other suitable options exist. They’ll have to pay for the drug themselves and recognize that there could be risks since the drug hasn’t been approved yet," Doblin explains.

"To qualify for the trial, patients will need to have PTSD and tried multiple therapies that didn’t work. MAPS is training therapists to work with MDMA, and it’s setting up expanded access sites around the country," Doblin says.

While Doblin’s trying to make up for time lost to restrictive drug laws, Heifets worries about moving too fast. “MDMA might work for a lot of people, but there’s going to be a large subset for whom it may create problems,” he says. The clinical trials exclude people with conditions that MDMA might exacerbate, and they give the drug under closely supervised conditions. Using pure MDMA in this way has revealed minimal risks.

That’s not what concerns Heifets. Rather, he’s concerned about what might happen if MDMA is given in unrestricted, unsupervised settings. "Say therapists use the drug without following the carefully crafted MAPS protocol. Who will help people manage the tidal wave of emotions that come up without feeling overwhelmed? Plus, some psychiatric drugs don’t mix with MDMA, so patients will have to be weaned off their meds," Heifets says. “Who’s watching that process? We’re in new territory here.”

"Ideally, everyone who provides MDMA-assisted therapy will have received MAPS training. But expanding use from a few hundred to the millions of people with PTSD raises the potential for a susceptible person to have a bad reaction that triggers another government backlash,"
Heifets says. “How are we going to avoid that outcome this time?”

That’s why he wants to focus on nailing down the brain networks associated with MDMA’s heightened feelings of emotional closeness and empathy. Learning how MDMA works could point to other treatments, maybe ones with fewer risks.

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Heifets knew he wanted to study the brain from an early age. But at medical school, he grew increasingly frustrated with his profession’s failure to help people. During a rotation at the Bronx Psychiatric Center, where most patients had failed to respond to every treatment offered, it hit him just how little doctors knew about the roots of psychological distress. “I was so dissatisfied with our ability to do anything,” he says.

A stint in the operating room gave him hope that he could find a way to help people. "Psychiatrists are stuck with “wimpy,” often ineffective drugs that take weeks or months to kick in," he says. But anesthesiologists have access to the most powerful psychoactive drugs in the hospital and can monitor major changes in consciousness in ways that aren’t possible outside the OR. That’s when he started thinking: what if psychiatrists could harness potent consciousness-altering drugs to heal broken brains the way cardiologists use surgery to repair broken hearts?

“This is really where psychiatry meets anesthesia,” he says. Anesthesiologists rely on potent drugs that quickly alter consciousness so surgical patients don’t feel physical pain. Similarly, psychiatrists working with drugs like MDMA can harness fast-acting mind-bending drugs to mold the brain’s perception of psychological distress. Researchers reported 20 years ago that MDMA, in the proper therapeutic setting, alleviates the fear that prevents patients from revisiting traumatic events, a vital part of the healing process. Exactly how MDMA does that still remains unclear.

A few years ago, the Department of Veterans Affairs declared psychotherapy to be the definitive treatment for PTSD; conventional drugs mostly just mask symptoms. But therapy often fails because people can’t bear to relive their trauma. Studies show an increased risk of suicide for veterans with PTSD. Effectively, people are dying for want of better therapies. The success stories from when MDMA was still legal convinced second-generation researchers like Michael Mithoefer that the drug might jump-start the psychological healing process. But whether it could pass muster as a standard treatment had never been pursued in formal research until Mithoefer, a clinical assistant professor of psychiatry at the Medical University of South Carolina, launched the first study with MAPS nearly two decades ago.

Today Mithoefer, a PTSD specialist, is overseeing clinical trials of MDMA-assisted therapy for hundreds of patients at 15 sites in North America and Israel. If all goes well in these formal studies, MDMA could get the green light from the FDA as a prescription drug for PTSD within two years. He’s cautiously optimistic. “We have to wait to see the results before we can say that we’ve definitively established safety and efficacy,” Mithoefer says. “It’s looking promising, but we need to see what happens.”

To get FDA approval, Mithoefer and his team don’t have to show how MDMA works. (“If we did, Prozac would never have been approved,” he says.) "Still", he says, "there may well be other drugs that are even better than MDMA."

As far as MAPS’s Doblin is concerned, there’s no point in trying to find another MDMA-like drug when the real thing is showing such progress. “Alexander Shulgin tinkered with the molecule in hundreds of different ways, but ended up feeling that of all the ones that he did actually produce MDMA was still the best at what MDMA does,” he says.

Doblin allows that drug companies could potentially improve on MDMA. But they’ve shown little interest in a controlled substance with an expired patent that can’t deliver a fast return on investment. And nonprofits like MAPS don’t have the resources to invest in drug discovery or to produce the amount of safety data the FDA requires.

A lot of that safety data, ironically, came from government efforts to demonize the drug, to no avail. “Big governments all over the world have spent hundreds of millions of dollars trying to identify the risks,” Doblin says. “So we have summarized the world scientific literature on MDMA and presented that to FDA.”

Aside from elevated heart rate and blood pressure, the risks include overheating and water intoxication. But it was nothing like the long-term brain damage NIDA seemed so intent on proving. Doblin envisions a day when MDMA will be available far beyond the clinic for everything from couples therapy to personal growth.

It’s a prospect that concerns some psychiatrists, including Charles Grob who led a recent study using MDMA to ease severe anxiety in autistic adults. "The idea of millions and millions of people taking MDMA “makes me dizzy,” says Grob, director of the Division of Child and Adolescent Psychiatry at Harbor-UCLA Medical Center, Los Angeles. "MDMA needs to be administered by trained professionals in special settings with clear-cut safety parameters," he says. Without these measures in place, he worries about “the whole enterprise going off the rails.”

Marcela Ot’alora, who runs the MAPS PTSD study in Colorado, agrees that MDMA may not be for everybody. About three-quarters of PTSD patients in her study learned to cope with their symptoms, but that leaves a quarter who did not. “It’s great if we can find something else that maybe would help people that are not going to be helped by MDMA,” she says.

That’s another thing that suggests Heifets’ approach might be a good one: finding better treatments depends on getting a better handle on how they work, which is insight that’s missing for most psychiatric drugs.

"Scientists stumbled upon the original antidepressants by accident: patients who took new drugs for tuberculosis in the 1950s reported feelings of euphoria. That led to theories about tinkering with neurotransmitters to improve moods and decades of drug development. That pipeline, however, is now dry," Heifets says.

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Both Prozac — a selective serotonin reuptake inhibitor (SSRI) — and MDMA affect the same brain chemical: serotonin, which regulates mood, learning, and memory. But no one gets an insatiable urge to approach strangers after taking Prozac, Heifets points out. Clearly, they act in different ways.

"Psychiatrists have long treated the brain as a chemical soup and enlisted drugs to target one chemical after another," he says. "But those drugs can cause terrible side effects because they’re not specific enough. Increasingly, researchers view psychiatric disorders as changes in the connections between specific groups of cells, or circuits, in the brain. Different regions of the brain talk to each other to support normal responses to everyday events, like meeting strangers or navigating potential threats. When those lines of communication between circuits break down, normal responses do, too. Figuring out how MDMA changes these connections to enhance emotional closeness may help explain what goes wrong in people who can’t manage social situations," Heifets says.

"In general, psychiatry hasn’t paid much attention to how social factors affect mental health," says Harriet de Wit, director of the University of Chicago’s Human Behavioral Pharmacology Laboratory. "Yet depression, schizophrenia, and psychosis, for example, share a strong sense of withdrawal from social interactions and society, even though the underlying process likely differs," she says. "A better understanding of how MDMA works might point to other drugs that can specifically affect the different social processes."

Heifets has been trying to do just that under the guidance of Malenka, a leader in enlisting cutting-edge tools in rodents to understand how changes in brain circuits affect behavior. “Rob’s been my biggest advocate and mentor,” Heifets says. “I’m the only one in the lab working on MDMA.”

“This is where Boris and I bonded,”
Malenka says. “It’s just a fascinating drug that I’ve been wanting to study for, my god, probably over 30 years because I think it’s a window into the brain and how the brain works.”

Malenka believes MDMA could ultimately help people whose illness makes healthy social interactions difficult or impossible. “Imagine going through life where you can’t have a positive social experience,” he says. “MDMA really taps into something that enhances the ability to have the most positive social experience.” But where Doblin sees a role for MDMA for everything from PTSD to personal growth, Malenka sees a powerful compound with the potential to harm as well as heal. "That’s not demonizing the drug," he says, "but recognizing the need to understand the good and the bad." For Malenka, MDMA is like any other substance that can affect brain function. "Drilling into the details of how it works will help clinicians make rational decisions about how to use it," he says.

Toward that end, Malenka hopes the experiments they’re doing in mice will influence the clinical studies by showing, for example, that a specific brain circuit isn’t functioning properly in a specific psychiatric disorder. That, in turn, could suggest new therapies that drug companies would be willing to invest in.

Recent work from Malenka’s lab shows that the release of serotonin in a region of the brain’s “reward circuit” — which reacts to pleasurable activities like eating and sex — can enhance social behavior in mice bred to have autism-like behaviors. Research from other groups working in mice showed that MDMA increases “fear extinction,” a decline in fear responses triggered by trauma, which appears to be critical for successful PTSD therapy.

"MDMA may be acting like a sort of psychological accelerant, hastening changes in the brain that lay the groundwork for recovery. The idea of starting a process as a bridge to healing is a concept that’s been missing in psychiatry," Heifets says. "The trick is figuring out novel or existing drugs that can build that bridge. We probably have a ton of drugs that are already FDA approved that we just don’t know what their potential is,” he says.

Beyond exploring how MDMA works in the brain, psychologists are still figuring out how it works in the therapist’s office. “We’re still kind of waving our hands around,” says de Wit. “There’s general agreement that it’s not just the drug itself, but it’s the combination of how the drug changes the therapeutic interaction. I don’t think we know enough about what happens in therapeutic interactions to know whether it’s something about the connection that the patient feels with the therapist or their willingness to be open about their emotions or whether they feel less judged.”

Whatever is going on is a radical departure from standard psychiatric treatments. Rather than taking SSRIs indefinitely to keep symptoms from returning — assuming they ever go away — patients take just a few doses of MDMA in therapy and experience lasting relief.

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At the Oakland Psychedelic Science meeting, where Heifets spoke two years ago, several practitioners emphasized the power of the relationship between therapist and patient to aid recovery. Psychiatrist Philip Wolfson, who urged the DEA to keep MDMA legal in the 1980s, said that MDMA revolutionized psychotherapy in part because therapists had to stay with people for as long as they needed. “That meant we exposed ourselves more as therapists,” he said. “And we changed from the 50-minute hour, which was always repugnant to me.”

Wolfson reported preliminary results from sessions using MDMA in 18 patients facing life-threatening illnesses. His study, like other MAPS-funded studies, involved intensive psychotherapy lasting at least eight hours in three sessions. The initial analysis for a subset of patients showed marked improvement in scores for both depression and fear of dying for those who took MDMA. But patients who took placebos also improved, a result Wolfson attributed to the effects of such intensive psychotherapy. Even so, after he recently finished the full analysis, it was clear that the MDMA group had the bigger drop in anxiety compared to the placebo group. Everyone had the option to do a follow-up MDMA session, he told me. Everyone opted for MDMA, and everyone felt even better as a result.

Ot’alora, the PTSD researcher who handled the compliment on her aura without missing a beat, has seen similar therapeutic breakthroughs without MDMA. But it can take years. "With MDMA sessions, people often show improvement right away," she says, "as the drug gives them the inner resources to work through their trauma. Even people who still had trouble coping with their PTSD symptoms after the treatment said it helped them when nothing else had," she says. “Every single participant I’ve worked with has said, ‘I don’t understand why this is not available to everybody who’s suffering.’”

Researchers feel buoyed by the promising results. Yet they’re keenly aware of the stigma around drugs like MDMA. “Now we have data saying that, yes, this is actually helping. It’s no longer anecdotal,” says Ot’alora. “And there are still people who are incredibly skeptical.”

Blame George Ricaurte’s fateful lab blunder. It doesn’t matter that his paper was retracted. It’s still on the internet, including the NIDA’s website. "Even today," Ot’alora says, "people tell her they read that MDMA causes holes in your brain. And she’s seen both patients and parents of younger patients bristle at the idea of using what they see as a club drug for therapy — until they see the results."

For years, meetings like Psychedelic Science were the only place scientists researching psychoactive drugs were invited to speak. “The government and industry have not put one cent into this research, so it has to be supported by donors,” Mithoefer says.

"Still, attitudes among psychiatrists have changed radically since the first MDMA studies," Mithoefer says. Now, he and his colleagues are presenting their work mostly at mainstream meetings where he’s seeing a lot of excitement around the idea that drugs like MDMA can trigger a therapeutic process with higher rates of success. “And nobody’s bringing up their auras,” he says with a laugh.

And now, scientists who study MDMA don’t have to worry about throwing away their careers.

For Heifets, one of the most intriguing things to come from lab work on MDMA is the notion that a drug can strengthen the bond between patient and therapist. “There’s no real precedent for that in psychiatry,” he says. "And that may be where the path to transforming psychiatry begins: in abandoning the notion that you can treat complex human brain disorders with drugs alone. It’s time to recognize that you can’t treat millions of veterans with PTSD by giving them a pill, whatever it is, and sending them home," Heifets says. "The research on MDMA is showing that you might be able to kick off recovery with a drug, but interaction with other people matters, too. In fact, the relationships with other people — like therapists — may matter even more."

“Fundamentally, there is a need for some kind of human connection,”
he says. “We can’t just farm out all of our psychiatric issues to the drug industry.”

 
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The pitfalls and challenges of Psychedelic Medicine

by Joshua Falcon, MA | Psychedelic Science Review | 10 Mar 2021

Psychedelics present some unique epistemological and ethical challenges.

In a recent opinion piece written by Matthew W. Johnson of the Johns Hopkins University School of Medicine, it is suggested that psychedelic researchers should take heed of three pitfalls that commonly arise in the practice of psychedelic medicine.

According to Johnson, these challenges include 1) working with limited conceptions of ‘consciousness’; 2) introducing personal religious or spiritual beliefs, whether intentionally or inadvertently, into the practice of psychedelic medicine; and 3) maintaining a disposition of ‘psychedelic exceptionalism’ regarding how strictly ethical and clinical boundaries should be adhered to. The following sections of this article delve into greater detail of each of these challenges, including Johnson’s suggestions on how to enhance future research practices with psychedelics.​

1. Use of the term ‘consciousness’

The term ‘consciousness’ is regularly evoked in psychedelic literature given the effects that classic psychedelic substances have on human perception, cognition, and experience. Since consciousness is an inherently ambiguous concept, Johnson argues that research that fails to define consciousness in precise terms may lead to misleading assumptions. If consciousness is used to refer to a range of phenomena, it can result in the belief that distinct phenomena are in fact identical, resulting in what Johnson refers to as a jingle fallacy.

As a way of avoiding this pitfall, Johnson proposes that researchers draw from the discipline of philosophy which has developed comprehensive treatises on the subject of consciousness. Drawing on the work of philosopher David Chalmers, Johnson suggests that the “hard problem” of consciousness, or the problem of explaining the nature and existence of experience itself, is currently out of the reach of the empirical sciences. However, Johnson also argues that many of the “easy” problems of consciousness, or the contents and processes associated with consciousness, can be fruitfully investigated by psychedelic researchers as long as they adopt more systematic and nuanced approaches to their use of the term consciousness.​

2. Improper introduction of spiritual or religious beliefs

A second pitfall that clinicians and scientists alike must remain wary of is introducing their personal spiritual or religious beliefs within the context of psychedelic medicine. As with the term consciousness, ‘spiritual’ can refer to a variety of things that may range from non-empirical supernatural belief systems to empirically verifiable beliefs such as caring for one’s friends and family. According to Johnson, researchers and practitioners in the practice of psychedelic medicine should focus on empirically based and secular meanings of ‘spiritual’ since these factors have been shown to positively contribute to psychological health and wellbeing.

Aside from remaining mindful of the concepts introduced to study participants, Johnson also urges clinicians and scientists to avoid incorporating religious iconography or symbols into the spaces of their clinical practice. For Johnson, the issue lies not in the researcher having their own personal belief systems, but in introducing those beliefs into therapeutic practice. The goal for clinicians and researchers is to ensure that patients have a supportive and open environment in which to make their own meaning during psychedelic therapy sessions.​

3. Ethical and clinical dilemmas

A final challenge that commonly arises in the practice of psychedelic medicine involves what Johnson refers to as ‘psychedelic exceptionalism’, or the belief that psychedelic substances and experiences need not adhere to the regular protocols and boundaries established by clinical psychology, medicine, ethics, and philosophy of science.

By disregarding or altering the longstanding guidelines and best practices developed in clinical psychology and medicine, researchers expose their participants to greater potential risks such as abuses of power or other inappropriate behaviors, given the suggestibility of psychedelic experiences and the vulnerabilities they may present. Furthermore, a belief in psychedelic exceptionalism is one of the errors that was committed by some of the early psychedelic researchers in the United States during the 1960s.​

Discussion

Johnson’s advice to researchers, clinicians, and others working in the field of psychedelic medicine is to maintain as transparent a process as possible while also adhering to proven and longstanding professional boundaries. While Johnson encourages the study of phenomena associated with consciousness, he suggests that researchers should proceed by way of specifying operative definitions of consciousness drawn from philosophy.

For scientists interested in how psychedelic experiences might potentially change one’s personal philosophy, Johnson warns against conflating these personal philosophies and beliefs with validity. Finally, clinicians and practitioners should avoid the use of religious icons in the practice of psychedelic therapy, as should they avoid introducing personal, nonempirical beliefs whether they be religious or spiritual in nature.

 
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Psychedelic Science holds promise for Mainstream Medicine

by Tony Allen | University of Nevada | 8 Mar 2021

UNLV neuroscientists Dustin and Rochelle Hines join rising number of researchers studying possible medical benefits of psychedelics; their work on brain activity recently published by Nature: Scientific Reports.

Psychedelic healing may sound like a fad from the Woodstock era, but it’s a field of study that’s gaining traction in the medical community as an effective treatment option for a growing number of mental health conditions.

While the study of psychedelics as medicine is inching toward the mainstream, it still remains somewhat controversial. Psychedelics have struggled to shake a “counterculture” perception that was born in the 1960s, a view that had stymied scientific study of them for more than 50 years.

But that perception is slowly changing.

Mounting research suggests that controlled treatment with psychedelics like psilocybin mushrooms, LSD, and MDMA – better known as ecstasy – may be effective options for people suffering from PTSD, anxiety disorders, and depression. The U.S. Food & Drug Administration recently granted “breakthrough therapy” status to study the medical benefits of psychedelics. And two years ago this month, the FDA approved a psychedelic drug – esketamine – to treat depression.

An increasing number of states and municipalities are also grappling with calls to decriminalize psychedelic drugs, a move that UNLV neuroscientist Dustin Hines says could further the recent renaissance in psychedelic science.

“The resurgence in interest in psychedelic medicine is related to multiple factors, including decreasing societal stigma regarding drugs like hallucinogens and cannabis, increasing awareness of the potential therapeutic compounds found naturally occurring in plants and fungi, and the growing mental health crisis in our nation,” says Hines.

“Because of the intersection between the great need for innovation and wider social acceptance, researchers have started to explore psychedelics as novel treatments for depressive disorders, including work with compounds that have been used for millennia.”

In the Hines lab at UNLV, husband and wife researchers Dustin and Rochelle Hines are uncovering how psychedelics affect brain activity. Their work, published recently in Nature: Scientific Reports, shows a strong connection in rodent models between brain activity and behaviors resulting from psychedelic treatment, a step forward in the quest to better understand their potential therapeutic effects.

We caught up with the Hineses to learn more about the evolution of psychedelic science — which actually dates back thousands of years — their research (which doesn't date back as long), misconceptions about this emerging field of study, and what to expect next.​


The scientific study of psychedelics holds great promise for people suffering with mental illness. Where do we stand?

Dustin Hines: It’s estimated that 1 in 5 American adults suffer from some type of mental illness. And while not all require pharmacological treatment, unfortunately there’s been limited progress in advancing novel therapies for depressive disorders in 50 or more years.

Rochelle Hines: It’s also worth noting that available therapies for major depression are only effective in specific segments of the depressed population. That’s what makes the study of psychedelic compounds so fascinating. Recent clinical studies have empirically demonstrated that these compounds can exert rapid antidepressant effects – essentially bringing into the clinic a practice that Mesoamerican and other cultures have used for thousands of years. But there are still quite a few regulatory barriers that limit even research use of psychedelics. We’re hopeful that as the public view of psychedelic compounds changes, so too will the federal regulations that currently govern their study.

Current therapies for mental health disorders can take weeks to become effective. Recent research, including your own, shows the potential for psychedelic compounds to work much more quickly. What do we know about how this happens?

Rochelle: Clinical research on the use of psychedelics as therapeutics suggests that they work by altering the connectivity, or communication, between brain regions. Multiple studies suggest that the connectivity of cortical sensory regions and other brain areas is strengthened. Studies have also reported alterations in the patterns of brain activity during psychedelic treatment in patients with depression.

Dustin: Our recent studies support the evidence for changes in patterns of brain activity, and provide additional detail into specific patterns of brain activity that are generated during psychedelic treatment. The brain activity patterns that we’ve characterized are related to specific behaviors known to occur following treatment with psychedelic hallucinogens. These findings support the idea that generation of specific brain activity patterns may be a key aspect of the beneficial effects that psychedelic compounds exert.

In your research, you discuss the long history of hallucinogens for ritualistic practices. What did these cultures know that we don’t, and how does your work draw upon this ancient evidence?

Rochelle: Modern medicine – which includes our research team – is reinvestigating psychedelic practices with a 5,000-plus year history. Mesoamerican practitioners are known to engage in specific processes that were honed over millennia of skilled use, often including the addition of nicotine to their ritualistic and therapeutic practices with psychedelics. At present, very little research has investigated the synergistic effects of psychedelics and nicotine.

Dustin: Despite this long history and recent clinical promise, we still really don’t know just how these drugs actually work on the brain to influence mood. This knowledge is essential to optimize their therapeutic potential. In our study of brain activity in a rodent model, we found that nicotine enhanced both the brain’s slow waveform as well as behavioral arrest, both hallmark aspects of the response to psychedelic hallucinogens. We’re now working on studies examining the synergy between psychedelics and nicotine, and whether nicotine enhances the anti-depressant effects of psychedelics.

Rochelle: We’re also investigating the cellular and molecular mechanisms that underlie the specific changes in brain activity following treatment with psychedelics. With this understanding, we may be able to further refine the clinical utility, applicability, and efficacy of psychedelic hallucinogens as medicines.

As researchers who study the possible therapeutic benefits of psychedelics, what are some of the biggest misconceptions you’ve encountered? How can further scientific study combat them?

Dustin: Microdosing of psychedelics — where users gain benefit, though not the prototypical “high” from small amounts the drugs is a practice that’s been in the news a lot lately. While there are some data suggesting that low doses can exert beneficial effects, the idea that a person can purchase controlled substances without clarity on the content of psychoactive ingredients and regulate their own dosing with precision is in my opinion misguided. By conducting research to examine both purified and synthetic compounds, we can more accurately establish dosing.

Rochelle: There’s a long-standing belief that these drugs are addictive. However, much of the research suggests that these drugs don’t result in maladaptive patterns of substance use behavior. To the contrary, some research actually suggests that these compounds may be effective in treating substance use disorders. More research on the effects of these compounds in models may provide better clarity on not only the acute effects, but the effects of repeated dosing.

Dustin: An important point to drive home with all of this is that psychedelics are powerful psychoactive drugs, and they should not be used for therapeutic purposes without an experienced practitioner.

The context surrounding the use of psychedelics as a therapy is emerging, but further research into the clinical use of psychedelics is needed to establish procedures and protocols that we hope will ultimately support positive outcomes for patients.

 
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The Future of LSD Psychotherapy

Stanislav Grof, M.D.

The Epilogue from LSD Psychotherapy, ©1980, 1994 by Stanislav Grof​

Hunter House Publishers, Alameda, California. ISBN 0-89793-158-0​


In the preceding sections of this book I have tried to express and illustrate my belief that LSD is a unique and powerful tool for the exploration of the human mind and human nature. Psychedelic experiences mediate access to deep realms of the psyche that have not yet been discovered and acknowledged by mainstream psychology and psychiatry. They also reveal new possibilities and mechanisms of therapeutic change and personality transformation. The fact that the spectrum of the LSD experience appears puzzling to most professionals and cannot be accounted for by the existing theoretical frameworks does not mean that the effects of LSD are totally unpredictable. The safe and effective use of this drug requires a fundamental revision of the existing theory and practice of psychotherapy. However, it is possible to formulate basic principles for LSD-assisted psychotherapy which maximize its therapeutic benefits and minimize the risks.

It is very difficult at this point to predict the future of LSD psychotherapy. The fact that it can be used safely and effectively does not automatically mean that it will be assimilated by mainstream psychiatry. This issue is complicated by many factors of an emotional, administrative, political and legal nature. However, we should clearly differentiate between the future of LSD psychotherapy and its contribution to the theory and practice of psychiatry. I mentioned earlier in this volume that LSD is a catalyst or amplifier of mental processes. If properly used it could become something like the microscope or the telescope of psychiatry. Whether LSD research continues in the future or not, the insights that have been achieved in LSD experimentation are of lasting value and relevance.

The theoretical formulations and practical principles that LSD psychotherapy has discovered or validated include a new, expanded cartography of the human mind, new and effective therapeutic mechanisms, a new strategy of psychotherapy, and a synthesis of spirituality and science in the context of the transpersonal approach. In addition, the recent rapid convergence between mysticism, modern consciousness research and quantum-relativistic physics suggests that psychedelic research could contribute in the future to our understanding of the nature of reality.

It is true that psychedelic experimentation has its dangers and pitfalls. But ventures into unexplored areas are never without risk. Wilhelm Conrad Roentgen, the discoverer of x-rays, lost his fingers as a result of his experiments with the new form of radiation. The mortality-rate of the early pilots who paved the way for today's safe jet travel was allegedly 75 percent. The degree of risk is directly proportional to the significance of the discovery, and its potential; thus the invention of gun powder involved a different level of risk from the development of nuclear energy. LSD is a tool of extraordinary power; after more than twenty years of clinical research I feel great awe in regard to both its positive and negative potential. Whatever the future of LSD psychotherapy, it is important to realize that by banning psychedelic research we have not only given up the study of an interesting drug or group of substances, but also abandoned one of the most promising approaches to the understanding of the human mind and consciousness.

The present prospects for systematic LSD research and its extensive use in psychotherapy look rather grim. It is difficult at this point to say whether or not the situation will change, though there are indications that the general climate might become more favorable in the years to come.

One of the major problems in LSD psychotherapy was the unusual nature and content of the psychedelic experience. The intensity of the emotional and physical expression characteristic of LSD sessions was in sharp contrast to the conventional image of psychotherapy, with its face-to-face discussions or disciplined free-associating on the couch. The themes of birth, death, insanity, ESP, cosmic unity, archetypal entities, or past-incarnation memories occurring in psychedelic states were far beyond the conventional topics of psychotherapy which emphasized biographical data. An average professional at that time felt reluctance toward or even fear of the experiential realms of this kind because of their association with psychosis. At present, intense emotional outbursts, dramatic physical manifestations, and various perinatal and transpersonal experiences are much more acceptable to and less frightening for many therapists because they can be encountered quite routinely in the context of the new experiential therapies, such as Gestalt practice, encounter groups, marathon and nude marathon sessions, primal therapy, and various neo-Reichian approaches. Many modern therapists value and encourage various dramatic experiences which in the framework of classical analysis would be seen as dangerous acting-out and considered a reason for discontinuation of treatment or even psychiatric hospitalization. Some modern approaches to schizophrenia actually encourage deep experiential immersion into the process instead of its chemical inhibition. For new therapists of the above orientation, psychedelics would naturally be the next step to help accelerate and deepen the process.

LSD entered the scene at the time of the psychopharmacological revolution, when new tranquilizers and antidepressants had their early triumphs and generated excessive hope for easy chemical solutions to most of the problems in psychiatry. At present much of the original enthusiasm in this area has tapered off. While appreciating the humanization of the mental hospitals and pacification of psychiatric wards which has brought their atmosphere close to that of general hospitals, it is becoming increasingly obvious that tranquilizers and antidepressants are, by and large, only symptomatic remedies. They do not solve the problems and in more serious cases lead to a life-long dependence on maintenance medication. In addition, there is an increasing number of professional papers that emphasize the dangers of massive use of these drugs—irreversible neurological symptoms of tardive dyskinesia, degenerative changes in the retina, or actual physiological addiction with a withdrawal syndrome.

We should also mention important social forces that might play a role in the future changes of policy toward psychedelic research. Many of the young persons who are in or will be moving into various positions of social relevance—as lawyers, teachers, administrators, or mental health professionals—had intense exposure to psychedelics during their student years. Those individuals who had experiences themselves, or had the opportunity to observe the process in close friends and relatives, will have formed an independent image and will not be dependent on second-hand sources for information. Elements of sanity in the new marijuana laws in many states may be the first fruits of this development. The fact that ritualized and responsible use of psychedelics received social sanction in some ancient societies and pre-industrial countries and was meaningfully woven into the social fabric represents a somewhat hopeful precedent.

 
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Medication



Psychedelic medicines for pain go mainstream*

by Frieda Wiley, PharmD | Drug Topics

An estimated 32 million individuals 12 years and older used psychedelic medicine in the United States in 2010, according to a US population survey. As the opioid epidemic has eclipsed concerns about illegal drugs in recent years, the medical community and the federal government alike have begun reexamining certain illicit drugs as potential alternatives to opiates in pain management.​

Cannabis

Cannabis has been studied extensively for its potential benefits in neuropathic pain, chronic pain, and inflammation. A 2014 study found that most patients cited relief from chronic pain as the most common reason for their medicinal use of cannabis. Yet the plant's psychoactive properties continue to draw concerns regarding abuse potential, owing to the effects of 1 phytochemical, Delta-9-tetrahydrocannabinol, known for its psychoactive properties.

However, these are not the only challenges pharmacists face when it comes to assisting patients. "The biggest pitfall in advising patients on cannabis is that dosing is so difficult to standardize," said Victoria Starr, RPh, a cannabis pharmacist at SageLife, LLC, in Portland, Oregon.

Cannabis for medicinal purposes is highly complex, largely because of its high number of phytochemicals, called constituents. To date, the plant has been found to contain more than 560 constituents. When individuals consume these as the whole plant, the chemicals offer synergistic and therapeutic benefits while mitigating potential toxicities, what's known as the entourage effect. Synthetic cannabis typically contains only 1 active ingredient and lacks additional chemicals that can help regulate undesirable effects. However, customizing cannabis dosing to even the individual patient is no small feat.

"Besides attaching medical benefits to each of these components, the combination of synergistic benefits needs to be determined, along with the proper ratio and dose," Starr explained. "So unlike Western medicine, in cannabis, there exists a multitude of different medications—with a wide range of potencies, targeting a vast array of medical conditions—made up of varied combinations of cannabinoids, terpenes, and flavonoids."​

Psilocybin

Psilocybin, the primary ingredient found in mushrooms that produce psychoactive effects, in enjoying an increased share of popularity and renewed exploratory use.

"It’s exciting that patients are starting to ask their pharmacist about psilocybin,” said Emily Kulpa, PharmD, an integrative health pharmacist and psychedelic medicine consultant based in Milwaukee, Wisconsin.

Although psychedelic mushrooms have been used for millennia, they gained popularity in the United States for recreational use during the 1960s and had spawned some academic interests as well. From 1960 to 1962, psilocybin, along with psychedelic relatives LSD and mescaline, became the focus of a series of trials known as the Harvard Psilocybin Project. At the time, these drugs were legal. Criminalization of these drugs would later erupt in the following decade as safety concerns grew.

Fast-forward to the new millennium. Psilocybin sparked some interest in its potential analgesic effects in cluster headaches and migraines. Psilocybin agonizes the 5-hydroxytryptamine receptor and may interact with nociceptive and antinociceptive processing. The results from one 2016 retrospective study Googling the keywords “cluster headache discussion forums” and “migraine discussion forums” found that patients who self-treated themselves with psychedelic tryptamines such as psilocybin and LSD reportedly experienced a reduction in cluster frequency and severity.

Although these claims may warrant clinical study in pain management, research has focused on the role of psilocybin in mood disorders. Kulpa credits events in popular culturwith helping bring psilocybin into the mainstream. In the fall of 2019, Johns Hopkins announced the opening of the Center for Psychedelic & Consciousness Research, the first institution in the United States devoted exclusively to psychedelic research.​

Kratom

Indigenous to Thailand, Malaysia, Myanmar, and other regions of Southeast Asia, kratom (Mitragyna speciosa) belongs to the coffee family and also exhibits dose-dependent sedative and stimulatory effects. The plant is typically consumed in pill, capsular, or extract form, although some individuals brew dried or powdered leaves as a tea. Others may chew, smoke, or consume the leaves in food. However, because of kratom’s harmful adverse effects and abuse potential, the FDA warns individuals against using the substance.

Kratom contains mitragynine, an alkaloid bearing a tryptamine-like structure that exhibits µ- and ∂-opioid receptor agonist activity that results in dose-dependent stimulatory and analgesic effects. In lower doses, mitragynine produces stimulatory effects, whereas higher doses result in opioid-like activity. However, its metabolite, 7-α-hydroxymitragynine, exhibits significantly stronger µ-opioid receptor agonist behavior.

Although kratom is not an opioid, the CDC found an association between kratom use and overdose deaths, also involving opioid and nonopioid use, in the State Unintentional Drug Overdose Reporting System. Moreover, based on toxicology results, medical examiners or coroners determined kratom as the culprit in deaths in 11 states from July 2016 to June 2017 and 27 states during the last 6 months of 2017.

“There is no legitimate medical use for kratom in the US,” the Drug Enforcement Administration (DEA) wrote in a report on its website. On August 16, 2016, the DEA announced its intent to classify kratom as a Schedule I controlled substance, noting that "kratom has been abused for its ability to produce opioidl-ike effects, and is often marketed as a legal alternative to controlled substances.”

Pharmacists should be aware of the substance so they can educate patients about the potential harms.​

Psychedelic medicine in the near future

Varanasi believes the importance of cannabis in pain management will only continue to grow. “Preliminary evidence demonstrates cannabis’ ability to provide significant pain relief as well as to help individuals taper off opioids particularly in the setting of addiction,” she said. “Though the research is inconclusive, patient anecdotes support the continued use of cannabis in pain management.”

In Oregon, the Oregon Psilocybin Program Initiative will appear on ballots in November 2020. “If passed, it would be the first state-sanctioned program for the administration of psilocybin services between a certified practitioner and a patient,” Varanasi said. “This would not only set the standard for other states but also support published studies reporting that a strong patient-practitioner relationship improves overall health outcomes.”

In the meantime, patients and practitioners alike will have wait to see how these and other psychedelics will alter integrative medicine and the world of health care.

*From the article here :
 
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