Transforming Psychedelics into Mainstream Medicines | +50 articles

[mr peabody]

The Psychedelic Divide​

Growing interest in psychedelic therapy reveals two different visions of the future: one of spiritual interconnectedness and one of sober neurochemistry.

by Marianne Apostolides | NEO-LIFE | 11 Feb 2022

Two competing visions of the future of psychedelics reveal much more than a mere debate about drugs—legal or otherwise. They symbolize larger ideas whose evolution reflects how we perceive ourselves at this moment in history, and what societal changes could result.

On one side is a scientific view, where psychedelics are simply chemical compounds affecting the brain which, in itself, determines the emotions, motivations, perceptions, and actions of the person. In this “medical model” worldview, the mind is the brain, and a person is neither more nor less than the sum of their complex biological parts, which we can increasingly map, monitor, and alter with precision.

On the other side is a view of psychedelics that pays homage to the ancient ceremonial significance of these drugs, while also responding to our contemporary era. Under this “healing model” worldview, rules about morals and behavior are no longer imposed from above—not by God, the state, or corporate entities. Instead, they evolve in the same way nature evolves, through dynamic systems of interaction. That non-hierarchical interconnectedness drives decentralized, blockchain-powered concepts like Web 3.0 and cryptocurrency. It’s also the force governing the spread of COVID-19 and the effects of global climate change. Psychedelics bring those hard-to-see forces to light.

The chemical view

Statues of the Buddha line the window ledge of Bryan Roth’s office at the University of North Carolina. The psychiatrist and pharmacology professor invented a biological tool called DREADDs, which is now used in neuroscience labs across the world. “My lab invented it because I wanted to understand how psychedelics work,” Roth says.

The acronym, DREADDs, is short for Designer Receptors Exclusively Activated by Designer Drugs—a name that describes the way the tool works. Essentially, Roth created DREADDs by designing a neural receptor that no chemical in the human body could bind to; he then engineered the sole chemical capable of binding to that receptor. This created a biological switch that Roth could control, allowing him to turn neurons on or off, causing a cascade of reactions. The receptor he targeted was the G protein-coupled receptor (GPCR), a common class of proteins found in the human brain, and the one to which LSD binds.

In effect, Roth’s first DREADD let him precisely map the circuits and cells responsible for LSD’s action.

“A lot of people were trying to make these creatures,” Roth says, referring to DREADDs. He succeeded where others failed because he used a then-new method for drug discovery, called directed evolution. The power of this method is that scientists, not nature, decide which traits should survive through the evolutionary process.

Twenty years after Roth evolved a human protein through directed evolution, scientists are using the method to create everything from biodegradable plastics and clean energy to new medicines. The technique has gotten exponentially more sophisticated with advances in machine learning. The brute-force approach Roth used to create his first DREADD has been streamlined through AI. Instead of generating compounds in yeast, he can do so through his computer platform, called Ultra LSD. “We’re able to access this huge chemical space,” Roth says, since the compounds he’s evolving “don’t exist in the physical universe”—not until he chooses which ones to synthesize.

Roth is choosing LSD-like compounds whose binding actions cause the growth of dendrites—the neuronal spines that reach across the brain, connecting to other neurons—but don’t cause hallucinations.

This is the nub of the chemical view of psychedelics: that psychedelics are effective at treating mental illness because they induce dendritic growth, not because they initiate the experience of a trip.

Roth readily admits that psychedelics have therapeutic benefit, as shown by recent clinical trials. “It’s a gigantic effect,” he says. “They’re going to revolutionize the treatment of mental illness. No question. But wouldn’t it be great if you could just take a pill and the next day your depression would be gone? I mean, you may miss out on the mystical experience, but you wouldn’t be depressed anymore.”

Through Ultra LSD, Roth sought a drug that could do just that. He examined 11 billion chemical compounds, searching for those that could induce dendritic growth without hallucinations. After choosing a handful of the most promising candidates, he synthesized the drugs and tested them on mice. The results are currently under embargo since publication is pending in a peer-reviewed journal. All Roth can say is that he’s “very pleased” with the outcome.

Plastic fantastic therapeutics

Non-hallucinogenic psychedelics have been dubbed “psychoplastogens” by professor David Olson, a biochemist at UC Davis and co-founder of Delix Therapeutics, a company developing new drugs in this class for therapeutic use.

In stress-related conditions like depression, post-traumatic stress disorder (PTSD), and substance abuse, dendrites are often seen to “shrivel up,” Olson says. “If you think of neurons like a tree,” where the branches are dendrites and the leaves are synapses, “you basically lose all your leaves, and the branches get trimmed.” The neurons become less robust in communicating across the brain’s various regions. Psychedelics’ ability to rapidly regrow neurons, known as “plasticity,” inspired Olson’s work on psychoplastogens.

“The idea of harnessing neural plasticity to rewire neural circuits is a paradigm shift in neural psychiatry,” Olson says.

But plasticity isn’t uncommon, says Alex Kwan, professor of neuroscience at Yale University. Other psychoactive chemicals like cocaine and nicotine induce neural plasticity—as do ordinary neuronal development and lifelong mental processes like learning. Yet psychedelics are unique. “There’s something about psychedelics,” Kwan says. “What regions is it targeting, what cells it is targeting, why is this plasticity different?” To find out, researchers need to map the regions in the brain that feed all those new dendritic spines. That’s not yet possible, although Kwan is collaborating with an optical engineer to design a microscope to image neurons across the three-dimensional space of the brain, taking various simultaneous views to follow the elaborate, distributive structure of dendrites in a way that can’t be done with two-dimensional images. “This imaging technology—looking at a whole dendritic tree in a live animal—will give us a lot of new insight into how these drugs work.” Which, in turn, will shape the questions researchers ask, Kwan says.

The new microscope won’t be operational for a few years, but advances in microscopy have already altered researchers’ fundamental knowledge of the brain. Roth capitalized on a cutting-edge technique called cryo-electron microscopy to see LSD actively binding to its receptor—a goal he’d had since the 1980s. Even before this, though, Roth made the cover of Cell for his work on LSD binding. In describing his work at a conference, he mused that imaging data might make it possible to create a chemical analog of the psychedelic compound that would be non-hallucinogenic.

Representatives from DARPA were in the audience. Roth soon got a call from the government.

Roth says he’s “agnostic” about whether non-hallucinogenic psychedelics will have any therapeutic benefit. Only clinical trials can answer that question, he says. Even so, he’s optimistic, especially because of one fundamental idea: “LSD is just a drug,” he says. “It’s a drug. And when it interacts with neurons, those interactions are all biochemical.” In other words, the mechanism through which LSD works isn’t an “interaction with dark matter in the cosmos… It’s just interacting with the receptor.”

The interconnected view

For Rick Doblin, the director of MAPS, the most important interaction that can take place in a psychedelic experience is not between a drug and its receptor or between the neurons in the brain, but between two people: the person taking the drug, and the one guiding the experience—a therapist, friend, or religious leader, for example. Doblin is arguably the person most responsible for the reinvigoration of clinical research into psychedelic therapy because he was the first to systematically pursue a long-term plan to convince the FDA of the efficacy of these drugs according to the medical model.

Doblin has been working toward the legalization of psychedelics for decades, overcoming regulatory barriers by designing studies that address potential roadblocks to legalization, providing evidence that clears a path for further research or policy change. After forming MAPS in 1986, Doblin submitted five different protocols for MDMA clinical trials—and was rejected each time. He then stepped back, deciding to fund animal-toxicity studies while also supporting research on human safety, finding people who’d used MDMA to voluntarily undergo spinal taps to show that MDMA hadn’t adversely affected their health. These basic building blocks paid off, with the first FDA-sanctioned, phase 1 clinical trial with MDMA approved in 1994.

Doblin has shown an ability to ease institutional resistance, in part by forging alliances with organizations like the Department of Veterans Affairs, a body that’s diametrically opposed to the counterculture narrative of psychedelics’ past, but shares MAPS’s commitment to improving mental health treatment. Doblin can also connect with audiences from the FDA and members of Congress to the CBS Sunday Morning show and the magazine GQ. He comes across as honest and genuine, not hiding any ulterior motives or seeking to profit from the booming business of psychedelics.

Although MAPS’s public statements have focused on clinical trials and research, Doblin has never concealed the fact that he seeks more than the legalized prescription use of psychedelics for specific disorders like PTSD or anorexia. He’s always sought the legal and cultural acceptance of psychedelics—“it’s just that nobody paid attention until now!” he says. Nobody thought the day would come when psychedelics would be embraced by the mainstream. But somewhere in the past twelve months, he says, that day arrived.

Three windows into society’s mind

Doblin portrays three possible ways through which psychedelics will enter mainstream culture. The first is a continuation of religious freedoms enshrined in various U.S. laws, including the Religious Freedom Restoration Act of 1993. These laws grant exemptions to religions such as Santo Daime, whose ceremonies are centered on the drinking of ayahuasca tea.

The second way has attracted the most attention: psychedelic-assisted psychotherapy, where a person is prescribed a treatment for a specific disorder like PTSD or anorexia. The prescription covers the drug itself, but also multiple therapy sessions to “integrate” the experience, helping people incorporate the insights gained so they can apply that knowledge in their everyday lives.

Doblin, who says integration is essential to psychedelics’ therapeutic effectiveness, is one of many people advocating for health insurance coverage for psychedelic-assisted psychotherapy.

Not everybody has insurance, though, and the therapy is expensive. That’s why psychedelics need to be legalized, Doblin says: “Legalization gets around the fact that one-quarter to one-third of people in America don’t have insurance.”

In Doblin’s conception, a person would obtain a license after undergoing a supervised trip led by a certified therapist who would also provide information on safe use for future trips. Although this licensing system could be quite expensive, Doblin insists the fee would be low cost, if not free, subsidized by taxes collected on the legal sale of psychedelics. A similar system was put in place in Michigan when marijuana was legalized: $20 million from sales of the drug are earmarked, in the first two years, for research into PTSD treatments for veterans.

In one important way, the legalization of psychedelics would differ from that of cannabis: People would be able to use the drugs on-site. That would enable the spaces to become community hubs, developing their own vibe, some evolving into wellness clinics providing therapies of all kinds, others hosting arts events and dance parties, others acting as places for political engagement and training—whether about climate change, poverty, or even issues surrounding equity and diversity in the psychedelic community itself.

That particular notion—that a psychedelic space will arise organically, without top-down dictates—aligns with the views of Franklin King, psychiatrist and director of training and education at the Center for the Neuroscience of Psychedelics at Massachusetts General Hospital. He uses psychiatry as a microcosm representative of larger trends in society.

“I just came from the psychiatric emergency room,” he says, describing a scene where people come into the hospital and lose control of what happens to them. “I basically tell them what they’re going to do—you’re going to be hospitalized, you’re going to take this medication—and they receive it. That’s the medical model,” King says, “and it’s broken.”

In that traditional medical model—the “chemical” view of the future of psychedelics—the doctor prescribes a treatment, often in the form of a drug. “The drug isn’t unlocking anything intrinsic in a patient, it’s just doing something biological to treat symptoms.”

By contrast, the “interconnected” view of psychedelic therapy is premised on the fundamental ethos that each patient has an innate capacity to heal. “The medicine unlocks it, the therapist supports it. But it’s really a process that comes from the patient,” King says. To him, this is a prime example of society’s rejection of hierarchical structures of power, where truths are dictated from above. “It’s in politics, it’s in cryptocurrency, it’s in grassroots movements organized online. Psychedelics are a big part of that change.”

Zeitgeist drugs

The terrain of psychedelic use is now in flux, but the systems for bringing these drugs to the mainstream are likely to solidify by the end of the decade, with inklings coming in the next two years. By then, the FDA is anticipated to approve MDMA and psilocybin for prescription use: If current clinical trials proceed as planned, the FDA will consider an application to approve MDMA for treating PTSD in 2023, using the protocol that includes integration therapy, and will consider applications regarding psilocybin for treatment-resistant depression and major depressive disorder not long after. As for non-hallucinogenic psychedelics, both Olson and Roth expect phase 1 trials to begin in 2022.

The two visions detailed here could easily coexist, with one dominating the mindset of the medical profession and capturing the popular imagination while the other burbles along in the background.

Regardless of capturing the zeitgeist, these drugs are attracting investment interest. With the industry expected to reach $7.5 billion globally by 2028, investors are rushing into the field—and have no lack of companies to choose from. Big pharma, including Johnson and Johnson, is in the game but on the back foot as startups race forward, developing synthetic analogs whose properties range from non-hallucinogenic, such as those developed by Delix, to short-acting, such as some developed by current front-runner Compass Pathways. Patent disputes are already brewing as companies seek exclusive rights to everything from the drugs they develop to the methods of production—and even the music played in therapy sessions.

But business dealings are not new. What’s new—at least in the intensity and clarity of the conflict—is the division between neuroscience and the experiential. The chemical versus the interconnected.

The proponents of each future-of-psychedelics worldview don’t dismiss the other side’s position, they just see it as irrelevant to the predominant trend in society. Olson points to the millions of people who could benefit from synthesized drugs inspired by the neurochemistry of psychedelics. Doblin’s vision, by contrast, encompasses both hemispheres of the globe—not just the brain—maintaining that psychedelics manifest an understanding of the interconnected nature of environments, people, and societies. For him, psychedelics derive their power from the physical experience of the body in the world.

Ironically, this is also how Roth conceives of therapeutic change. When asked about the Buddha statues in his office, he mentions his Zen meditation practice, which typically produces benefits over time, he says, “and by having an entire lifestyle devoted to being a better person.” The process isn’t easy, he adds, saying, “Meditation isn’t user-friendly!”

And this might be the crux determining which of these visions shines brightest, and whether one (or both?) is just a flash in the pan. Namely, what will people do with the insights gained from these drugs? Will psychedelics and their non-hallucinogenic analogs invoke a change in behavior, on an individual and societal level? Or will it all be in our heads?

https://neo.life/2021/12/the-psychedelic-divide/

 

[mr peabody]

Psychedelics and their potential as medicines*

The Conversation | Neuroscience News | 21 Feb 2021

For many years, drugs such as LSD, psilocybin and Dimethyltryptamine (DMT) were viewed only as highly dangerous drugs. However, in recent years they have had a bit of rebrand. Now they’re believed by some to have the power to heal, to reconnect us with nature – even resolve political tensions.

Use of these drugs is on the rise. At the start of the pandemic in 2020, the UK Home Office released data showing a 230% rise in confiscations of LSD compared to the previous year. The pandemic itself might be changing drug preferences. Almost half of those using magic mushrooms reported using more during the pandemic according to a recent survey.

The changing view of psychedelics can in part be attributed to the renewed interest in their potential to treat mental health problems such as depression. Between the early 1950s and 1970s, there was a great deal of interest in the use of LSD in the treatment for a wide range of conditions, including alcohol use disorders, schizophrenia, childhood autism and “sexual dysfunction”.

Despite some promising findings, a lack of scientific rigour and wider political and cultural pressures meant that almost all research ended in America in the late 1960s, although it has continued in Europe.

This work has now started up again to a limited extent. As demonstrated with medicinal cannabis, emphasizing the therapeutic potential of a drug can help shift attitudes towards it. In recent years, as research activity has increased, media attention has moved from the risks associated with psychedelics to their potential benefits. This has helped reshape attitudes towards this group of drugs.​

Mind altering​

The gradual rebrand of psychedelics, from dangerous to therapeutic, has been bolstered by a booming wellbeing industry. An increasing number of people are looking for ways they can extend the mind, body and soul. This has led to a rise in companies selling herbal remedies (as seen with the popularity of turmeric touted as “nature’s-wonder drug”) and now even psychedelics.

Before the pandemic, psychedelic tourism was a growing niche of wellbeing. One popular strand was ayahuasca retreats in South America, which attracted thousands of wealthy customers keen to explore their psyche.

Ayahuasca has been used in traditional healing and spiritual practices for generations by South American indigenous populations. The potent brew contains DMT, the active ingredient that produces a powerful psychedelic experience. For a few thousand pounds travellers can engage in this practice and claim these celebrity-endorsed rituals as their own to address their physical, psychological and spiritual maladies.

While some are seeking spiritual awakening, others are using psychedelics to boost brain function.

Microdosing psychedelics, which involves taking small doses of the drug, has also grown in popularity. The aim is to enhance cognitive performance, without the disruption of a full-blown experience. People who engage in the practice claim it makes them more productive, creative and focused. The practice has been enthusiastically reported and promoted in media, despite little evidence of its effectiveness.

This has also helped reshape the image of psychedelics, with a focus on benefits – including savings to healthcare services – rather than the risk of harm. Access to psychedelics has never been easier via the internet and dark web markets.

Likewise, the recent decision by legislators in the US to reduce penalties for possession of small quantities of magic mushroom reflect the view that these substances are potentially therapeutic, distinct from many other controlled drugs that are discussed in relation to the harms that they can potentially cause.​

Big business​

Private industry, sensing a shift in attitudes and seeing there are profits to be made from legal cannabis in the US, are now setting their sights on psychedelics.

New companies have started up, supported by experienced investors and tech billionaires and advised by leading psychedelic researchers. The initial focus has been on patenting new techniques for synthesising psychedelic drugs and establishing private medical clinics and therapies to distinguish medical uses from “recreational”.

But as with cannabis, over the long term, as attitudes continue to shift, big money is also likely to be made in non-medical and wellness markets.

While we’re unlikely to see psilocybin hummus on our shelves, “wellness” is a trillion-dollar global industry. Whether that’s home microdosing kits, spiritual retreats, or “therapies” for people feeling lost and without direction, where there’s a disposable income, there’s a psychedelics company with an answer.

*From the article here :

From Trippy Drugs to Therapeutic Aids – How Psychedelics Got Their Groove Back - Neuroscience News

From microdosing to improve cognition to treating a range of mental health disorders, researchers evaluate the rise in the use of psychedelics and their potential as medicines.

neurosciencenews.com

 

[mr peabody]

Psychedelics are transforming the way we understand depression and its treatment

Psychiatry has long failed to explain depression. Our psilocybin research helps offer new answers.

by Robin Carhart-Harris | Irish Times | 7 May 2021

Mental illness is the 21st century’s leading cause of disability, affecting an estimated billion people across the world. Depression is the number one contributor: more than 250 million people have this condition globally. The number of people prescribed antidepressant medications, the first-line treatment for depression, increases each year, and the market for them is valued at approximately $15 billion (€12 billion). Yet depression prevalence rates have not decreased since accurate record-keeping began. One reason for this paradox is the failure of science to adequately explain how and why depression occurs.

Psychiatry has long sought and failed to find a compelling biomedical explanation for depression. One popular idea, the “serotonin hypothesis”, was inspired by the observation that drugs that increase the activity of this naturally occurring brain chemical have antidepressant effects. First produced in the mid-1980s, Prozac (chemical name fluoxetine) is the most famous selective serotonin reuptake inhibitor (SSRI) antidepressant. Of these, Cipralex (escitalopram) is one of the newest and best performing.

While the serotonin hypothesis has some scientific foundation, it has been massively oversold by the pharmaceutical industry. This has stoked scepticism about one-sided, neurochemical explanations for depression, which suggest, for instance, that people are depressed because their serotonin levels are too low. The latest evidence indicates that SSRIs such as escitalopram are only marginally more effective at treating depression than a placebo, with response rates tending to average about 50-60 per cent. Other limitations of SSRIs include poor compliance, symptoms when people stop taking them, unpleasant side-effects and a sluggish onset of antidepressant effects.

An alternative

I began investigating an alternative to antidepressant medicines about 15 years ago as part of my PhD. Psilocybin, a constituent of “magic mushrooms”, is a classic psychedelic. When taken in high doses, it profoundly alters the quality of one’s conscious awareness, producing complex visions and releasing suppressed memories and feelings. After completing a series of studies involving psilocybin, including an earlier trial of its effects among people with treatment-resistant depression, I set out to design a more rigorous test that might help to contextualise the drug’s therapeutic promise. The resulting trial was completed last year, and its findings have now been published in the New England Journal of Medicine.

It was a double-blind, randomised, controlled trial involving 59 people with moderate to severe depression. They were randomly allocated to one of two treatment groups: one in which the main treatment was a six-week course of the conventional SSRI antidepressant, escitalopram, and another in which the main treatment was two high-dose psilocybin therapy sessions.

Those in the escitalopram group did about as well as one would expect, based on previous SSRI trial data and the relatively short, six-week course. Across four different measures of depressive symptoms, the average response rate to escitalopram at the end of the trial was 33 per cent. In comparison, psilocybin worked more rapidly, decreasing depression scores as early as one day after the first dosing session. At the end of the trial, the average response rate to psilocybin therapy was more than 70 per cent.
​

The most exciting aspect of this trial is a sense that we are on the verge of a paradigm shift in mental healthcare linked to an improved understanding of the origins of depression.​

While we suspected that psilocybin might perform well compared to the SSRI, we had not expected it to perform as well as it did. In fact, the initial main hypothesis for this trial was that the psilocybin therapy would have superior effects on psychological wellbeing, but not on depression severity scores. This prediction was generally supported, but people in the psilocybin group also showed evidence of greater improvements across most depression measures, as well as anxiety symptoms, work and social functioning, suicidal feelings and the ability to feel emotion and pleasure.

Both groups experienced similar levels of side-effects, but the escitalopram group experienced worse drowsiness, dry mouth, sexual dysfunction and anxiety. In the psilocybin group, the most prevalent side-effect was a mild to moderate headache one day after dosing. Six-month follow-up work is now under way to test our prediction that the positive effects seen in the psilocybin group will be longer lasting.

So why does psilocybin appear to be a more successful treatment for depression than a typical antidepressant? Brain imaging data from the trial, alongside the psychological data we collected, appears to show that while SSRIs dampen emotional depth by reducing the responsiveness of the brain’s stress circuitry, helping to take the edge off depressive symptoms, psilocybin seems to liberate thought and feeling. It does this by “dysregulating” the most evolutionarily developed aspect of our brain, the neocortex. When this liberation occurs alongside professional psychological support, the most common outcome is a renewed breadth of perspective. Psychedelic therapy seems to catalyse a type of psychological growth that is conducive to mental health, overlapping in many respects with spiritual growth.

Paradigm shift

The most exciting aspect of this trial is a sense that we are on the verge of a paradigm shift in mental healthcare linked to an improved understanding of the origins of depression, and how we can most effectively treat it. In my view, this shift will take us away from an outdated and myopic “drug-alone” perspective that has dominated psychiatry for several decades, and towards a multi-level “biopsychosocial” model. This model sees the symptoms of depression as an adaptive response to adversity, with decipherable – albeit complex – psychosocial causes. Psychedelics can treat depression by activating powerful brain states that have evolved in humans to catalyse deep psychological change. When these “hyper-plastic” states are combined with a nurturing environmental context, defensive habits of mind and behaviour can undergo a healthy, potentially enduring revision.

These ideas aren’t confined to the academy. Since I wrote about developments in psychedelic medicine for the Guardian last year, the US state of Oregon has voted in favour of legalising psilocybin therapy, a senate bill has been introduced to decriminalise psychedelic drugs in California, and policies are also being reviewed in New York, Washington DC, New Jersey, Florida, Canada, Australia and the UK. The Australian government has pledged A$15 million (€9.6 million) to psychedelic research, while two new research centres dedicated to studying psychedelic medicine have been announced at major US universities. Of course, our study certainly isn’t a licence for people to self-medicate. But these are exciting developments – and show that governments are recognising the benefits of psychedelic therapies.

Many obstacles have already slowed the progress of psychedelic medicine, and there will doubtless be more, from litigation issues to moral objections. If we’re to achieve a population-level improvement in psychological wellbeing, this road won’t be easy. Despite the recent landmark trial, I do sometimes wonder if we will make it at all. One thing I am more certain of, however, is that we must try.

Psychedelics are transforming the way we understand depression and its treatment

Psychiatry has long failed to explain depression. Our psilocybin research helps offer new answers

www.irishtimes.com

 

[mr peabody]

Psilocybin Therapy and the Rise of Existential Medicine​

Does psilocybin therapy mark the dawn of a new era in mental health? A psychedelic researcher talks the future of existential medicine.

by James McClure | DoubleBlind | 18 Aug 2021

Over half a century has passed since the last heyday of psychedelic research. During the 50s and 60s, the therapeutic potential of psychedelics, like psilocybin, dazzled researchers and inspired hopeful psychonauts throughout the Western world. Now, a resurgence of research has once again fanned the prospect of psilocybin therapy—but will our society be responsible enough this time around?

Dr. Charles Grob certainly hopes so—and if there’s anyone who can explain the promise and pitfalls of psilocybin therapy, it’s Dr. Grob. His resume is impressive: Grob is a psychedelic researcher, professor of psychiatry and pediatrics at the UCLA School of Medicine, and co-founder of the Heffter Research Institute, which promotes the scientific research of psilocybin and other psychedelic compounds.

Emerging research suggests that psilocybin therapy may have therapeutic potential for various mental health conditions, including substance use disorder, treatment-resistant depression, and other psychological conditions that are historically difficult to treat with conventional therapy and medications. But, how does psilocybin therapy work, exactly? How is it conducted? And why does it seem to help patients when so many treatments have failed? We talked to Dr. Grob to get to the bottom of these important questions.

What is psilocybin therapy?

Psilocybin is the primary active compound found in magic mushrooms. It’s well-known for inspiring trippy visuals and eight-hour-long journeys into the psychedelic headspaceーbut that’s certainly not all. More recently, the compound’s potential to revolutionize Western mental health modalities is making headlines. Mental health professionals are exploring the feasibility of using psilocybin to facilitate healing during intensive psychotherapy sessions.

Right now, psilocybin therapy is restricted to a small number of scientific studies that are tightly controlled and closely monitored due to the substance’s legal status. Like many other psychedelics, psilocybin is strictly prohibited for both medicinal and recreational use in most states and most countries around the world: A fact that makes it difficult for most patients to safely access.

Preparing for a psilocybin clinical trial

Those who can participate in a clinical trial for psilocybin-assisted psychotherapy should also expect a fair amount of paperwork. Before taking part in one of these limited studies, participants must pass a medical background check.

“What we have done, and I think the other studies have often done this as well, is we’ve had between two-to-four screening and preparatory sessions” in which therapists inform participants of what to expect during a psilocybin trip. During this stage, the therapists might also help each participant determine the intention of their trip.

“I find it’s very important to look at the intention of the experience—to really help the patient articulate why he or she wants to have this experience,” Grob says. “What does he or she hope to gain from the experience?”

Once those preparations are complete, the participants are ready to take psilocybin, which is usually administered during a day-long treatment session with a facilitator. And instead of being given a handful of dried mushrooms—as is common when buying shrooms from the black market—participants usually receive encapsulated psilocybin.

“It would just be capsules,” Grob explains. “A research pharmacist would weigh out the quantity of the material and insert it into the cap.”

These doses are administered in controlled environments, which is common in psychedelic research. That means the participants take their psilocybin doses within clinical settings rather than at home. Some subjects, however, may not receive any psilocybin at all.

“We also have identically appearing capsules that contain an inert substance that is a placebo. All of these studies are placebo-controlled, and neither the subject nor the facilitator knows what they’re getting on any one occasion. Although in our study, we have our subjects act as their own control, so there was a crossover. Some of the subjects received the active medicine in the first session, and some of them received the active medicine in the second session. They would get the placebo, and at other times, they would get one of each, but what was blinded and randomized was the order in which they would get it.”

A randomized, placebo-controlled, and double-blinded study is considered the gold standard in scientific research.

How does psilocybin therapy work?

Psilocybin therapy entails so much more than the trip itself. Participants in these studies usually do not take psilocybin as the only form of treatment; the therapy is administered alongside traditional forms of psychotherapy. For instance, in a 2015 study testing psilocybin’s ability to treat alcohol abuse, participants took the psychedelic substance in combination with Motivational Enhancement Therapy (MET). MET is a form of therapy designed to help patients with substance-use disorders develop strategies to overcome addiction. Participants in the study completed four weeks of MET before taking their first psilocybin dose.

More recently, a 2016 study on smoking cessation tested whether or not smokers could overcome their nicotine addiction by combining psilocybin therapy with Cognitive Behavioral Therapy (CBT). This therapy can help patients with substance use disorders identify and overcome negative thought patterns that reinforce their dependence on drugs or alcohol.

In the following days and weeks, participants are usually brought back for several “integrative sessions,” during which participants discuss their trip with therapists. This integration period seeks to put the psychedelic experience in context and assess the effectiveness of psilocybin in treating the condition they are trying to manage.

What happens during a psilocybin therapy session?

There are no strict rules for running a session of psilocybin-assisted therapy. Still, researchers tend to stick to a similar set of guidelines to create the right setting for a psychedelic experience.

“It’s optimal to be in a quiet setting, a setting that’s aesthetically pleasing, and where you will not be intruded on by others,” Dr. Grob tells DoubleBlind.

A facilitator familiar with administering psychedelic compounds oversees the therapy process and knows when to encourage participants to discuss the experience and when it’s necessary to give them time and space to immerse themselves in the trip.

“A facilitator should understand how to conduct a proper session, which includes not being overly intrusive,” Grob explains. “That means being active and engaged at particular times, but at other times allowing the patient to go deeply into the experience. To the latter end, eyeshades are often used as well as headphones, which are connected to pre-selected music that’s appropriate for this experience.”

However, patients aren’t required to use any of that equipment, and many prefer to forgo the props.

“Not everyone is comfortable with a mask on or headphones,” Grob adds. “For the psilocybin study we did, we were working with people who were in very serious existential crises. They were approaching the end of their lives and were really wrestling with a lot of issues. We felt it was more important for them to go deep inside than sit up with eyes open and engaging us in conversation. So we would encourage them to go deeply into the experience and let them know there will be plenty of time at the end of the session to process what they’re experiencing.”

Psilocybin therapy for addiction, depression, and more

In preliminary research, psilocybin-assisted psychotherapy has shown promise as a treatment for substance use disorders, treatment-resistant depression, and other conditions. Yet, it is far too early to conclude whether or not the psychedelic compound works as a medical treatment for specific health conditions.

“The preliminary data is promising, but it’s still relatively early on,” says Grob, who believes that much more research needs to be conducted before making any conclusions about the effectiveness of psilocybin therapy. “We need to replicate these outcomes in far greater numbers of patients, and we need more research; different groups around the country—or around the world for that matter—to replicate these findings. And if they can’t replicate them, then we need to examine why that is the case.”

Despite those caveats, Grob notes that the results from recent studies are very encouraging.

“I think so far the results have either been positive or equivocal. I can’t recall seeing any negative outcomes reported. I would say at this point that treatment with psychedelics looks very promising; although, it’s not necessarily definitive. It looks promising, but we have to recognize we’re still relatively early on in our efforts to study this treatment model.”

He adds that in some cases, the effectiveness of psilocybin therapy is often easy to perceive based on obvious changes in a participant’s behavior.

“My approach has been to examine psychiatric conditions that often do not respond well to conventional treatments. For instance, alcohol abuse is a terribly, notoriously difficult condition to treat. Modern medicine really is still struggling to come up with effective treatments. So there it’s very clear to determine whether or not your treatment has helped or it hasn’t helped because either your subject continues to drink or he has stopped drinking.”

Why does psilocybin-assisted therapy work?

At this stage, it’s difficult to determine why psilocybin therapy seems to help patients grapple with addiction and depression. Still, Grob notes that many researchers believe that its effectiveness may have something to do with the spiritual nature of the psychedelic experience.

“The mechanism for therapeutic action in some recent studies are really on a continuum with one of the mechanisms suggested in the 1960s by Walter Pahnke and Stanislav Grof, which is that individuals undergoing the experience who have a powerful mystical experience—a powerful psycho-spiritual epiphany—these subjects are most likely to have therapeutic outcomes, meaning less anxiety, improved mood, improved overall quality of life. You know, no expectations that’ll affect the actual medical disease, per se, but it can, under optimal conditions, help an individual come to terms with the existential dilemma or crisis they’re in. So the idea of urging your patient to lie down, put the eyeshades on, put the headphones on, and go deeply into the experience—that’s to allow them the opportunity to have one of these powerful, spiritual experiences that on some occasions these medicines seem to induce.”

Grob says these theories are consistent with previous research from the 1950s and 60s.

“If you look at some of the more impressive studies from the 50s and 60s that worked with people with terminal cancer who were all facing an end-of-life existential crisis, the outcomes were very good. Not that their medical illnesses were resolved. That wasn’t the case at all, but their fear of death diminished, and their mood—in spite of their circumstances—improved, and their death anxiety dropped.”

Based on those findings, psilocybin may become a new option for palliative care, a hypothesis that Grob hopes to explore in his next study.

“I’m working with a few colleagues at other institutions, and we’re preparing a multi-site psilocybin treatment study for individuals with terminal medical disease or potentially terminal medical disease who are going through serious psychological crises. It’ll take place in the palliative setting, and we’ll be collaborating with palliative specialists.”

Will history repeat itself with psilocybin-assisted therapy?

The studies that Grob mentioned from the 50s and 60s offer support for current research as well as a cautionary tale for researchers. Psychedelic medicine looked promising back then until legislators shut down research due to a flood of controversial studies and the launch of the War on Drugs by former President Richard Nixon. While efforts to end the drug war have gained momentum across America in recent years, Grob warns that we could see psychedelic research shut down once again if researchers are not careful.

“I think we need to be attentive to the lessons of history and not repeat the mistakes of the past.” To avoid that fate, “facilitators need to behave themselves, not take advantage of the fact that during a psychedelic experience, the patient’s boundaries dissolve, so they’re more vulnerable,” says Grob. “There needs to be some attention given to make sure that therapists in this area are themselves screened and understand that a very strong code of ethics needs to be followed.”

Failing to meet those standards could result in psychedelics becoming demonized once again.

“There’s always a risk of these compounds falling into disfavor,” Grob adds. “That’s why it’s imperative that people working in this field maintain very strong integrity, high ethical standards, and really prioritize patient protection and maintaining strong safety parameters for patients. We should never lose touch with what happened several decades ago, when this very promising treatment hit the scene and was perceived as the cutting edge of psychiatric research and practice. Then it completely went off the rails. And the way I see it is our society was not sufficiently mature enough to handle these compounds back in the 60s."

“So here we are some 50 or 60 years later, and the question is, as a society, as a culture, have we sufficiently matured enough that we can handle these compounds, treat them with respect and care, maintain strong safety parameters, and be allowed to explore their potential to heal and inform? That’s the big question that awaits us.”

The future of “existential medicines”

Nobody knows for sure what the future of psilocybin-assisted therapy will look like, but Dr. Grob hopes that the process remains much the same as it is right now.

“To one degree or another, there needs to be a therapeutic component,” he says. “Having preparation, establishing rapport between the patient and the therapist, then the all-day session and then follow-up meetings between the facilitator and the patient to help with integrating the experience, I think that should be standard. This is not the kind of treatment where you give somebody a pill, tell them to take it, and report back to you what it did. That’s a dangerous approach. There is a greater likelihood of someone going off the rails if they haven’t been adequately screened or prepared if they’re not with a trained facilitator who can help them navigate what can be a challenging and disorienting terrain at times and who are not there to help the patient process, understand and integrate what he or she went through.”

If research continues to deliver positive results, Grob thinks psilocybin and other psychedelics may one day be recognized as “existential medicines.”

“These substances can be perceived as existential medicines that address the heart of the existential crisis, which is a loss of a sense of purpose and meaning to life. The optimal psychedelic experience can address this existential crisis and restore a sense of meaning and purpose. So that’s another kind of perspective that this is existential medicine and what’s being addressed [through the psychedelic experience] is the great existential dilemma that all people inevitably have to go through.”

That crisis is felt most by people already dealing with terminal cancer and other conditions that will eventually claim their lives, which is why Grob is particularly interested in using psilocybin therapy with these patients.

“People who are quite ill and actively starting to enter into a process that will eventuate in their dying, they’re dealing with the great existential dilemma in the here and now. These people have lost the thread of that identity as they’re going through the crisis of becoming ill, going through all the treatments, and now entering a final phase or approaching a final phase.”

For those patients, psilocybin-assisted therapy could make life not only bearable but meaningful again, according to Grob.

“This model—when properly administered to properly screened and prepared patients—seems to have the facility of restoring this sense of meaning and purpose and sort of restoring a sense of identity that one has had throughout the course of their lives.”

Psilocybin Therapy and the Rise of Existential Medicine

Does psilocybin therapy mark the dawn of a new era in mental health? A psychedelic researcher talks the future of psychedelic medicine.

doubleblindmag.com

 

[mr peabody]

Cambridge

How psychedelic mushrooms went from Schedule I to psychotherapy

by Isabelle Williams | The Pacific Index | 8 May 2021

Anne Marie Backstrom, Oregon legislative aid and Education Director for Yes on Measure 109, was singular in both enthusiasm and experience as far as political lobbyists go. She wore her hair in a dark green bob, and opulent piercings glimmered on either side of her nose as she admitted that she wasn’t active in drug policy advocacy until a few months before the vote on measure 109. At the point by which she joined the Yes on 109 team, she had become enamored with the idea of psilocybin mushrooms in the context of psychotherapy. She explained that, in all of the stories she had heard of others getting involved in activism because of the measure, she did not feel alone in being late to the party. Many volunteers and leaders with Yes on 109 had gotten involved mere weeks before the measure passed, as well. However, there are those sporadic occasions when a one-in-a-million measure is proposed and arouses an unusual amount of public interest. Measure 109 became that absurdly popular proposition for Oregon in Autumn 2020. Backstrom helped lead the campaign that saw Oregon Ballot Measure 109 through the state legislature after only becoming involved as Education Director 3 months before a vote was cast.

Through the cold light of a computer screen, warmth and spectacular ease exuded from Backstrom. Her eyes ignited from behind emerald-colored fringe, and a smile occupied most of the rest of her face. Her gestures and words started small and simple, her black painted nails lightly circling the air around her. However, as the memories of her involvement with Yes on 109 came flooding back into recollection, her gaze wandered up and out from her computer camera.

Her hands moved wider in sweeping, conductor-like motions, and she began to place extra emphasis on words like “so” and “totally.”

She explained that she began as a volunteer for Yes on 109. Her first job with the campaign was to make cold calls to constituents every day.

“I only signed up to volunteer,” said Backstrom. “I helped gather petition signatures in the pandemic, which was a trip.” She took a moment to laugh at her unintentional pun. “I’d never done something like that.”

Now, after months of effort and tireless exertion, Backstrom has become one of the most essential players in the implementation of Oregon Ballot Measure 109, a measure that totals around five years in the making. This measure officially established the foundation of programs for the therapeutic distribution of psilocybin in Oregon and the Oregon Psilocybin Advisory Board (OPAB). In cooperation with the Oregon Health Authority (OHA), "the board will license the manufacturing, transportation, delivery, sale and purchase of psilocybin products and the provision of psilocybin services” according to the official language of the measure. Accomplishing the implementation of such an unusual piece of legislation is a tall order, and Backstrom seems humbly aware of that undeniable truth. “With my personal experience with mental illness,” said Backstrom, “I just felt like this was something I had to jump on. Mental healthcare advocacy is deeply personal to me, so this kind of cause and community is something I really have deep ties to.”

The idea for the measure came about in 2016 when married Portland-based therapists Tom and Sheri Eckert began researching the benefits of psilocybin in their field. The two became outspoken advocates for psilocybin therapy in Oregon, thus creating the Oregon Psilocybin Society (OPS): a nonprofit organization that proposed and supported Measure 109 as a 2020 proposed ballot measure. Yes on 109 eventually became the campaign for the ballot measure led by the OPS to eventual success. The measure made the ballot successfully on November 3, 2020, much to the Oregon public’s surprise. According to the OHA, the ballot directs them to license the “manufacturing, transportation, delivery, sale and purchase of psilocybin products and the provision of psilocybin services”. The development of the regulations is to occur over two years spanning from January 1, 2021, to December 31, 2022. The OHA must begin the licensure process with qualified psychedelic treatment practitioners by then.

Backstrom had already been following this growth and development of Measure 109 through her job as a Legislative Aide for State Representative Ken Helm. She entered the fold as Education Director after Sam Chapman, the Director for Yes on 109, singled her out as a perfect candidate for Education Director. The prime goal of the campaign when Backstrom signed on in August of 2020 was to reach voters who were not expected to vote for the measure at all. Backstrom recalled that “In these conversations, we would start with a lot of resistance. It was usually, ‘Oh my God! That’s a drug!’ Being able to walk it back and really talk people through the fact that psilocybin is a therapeutic tool was really important.” These target voters were often older women who lived in more rural communities, whose political ideologies ranged from moderate to independent. “We didn’t really want to talk to the people we knew would be with us: young progressives and people living in the Portland Metro area,” Backstrom said of the campaign strategy. This was no mean feat for Yes on 109, especially as an organization that relied heavily on volunteer legwork to make a measure legalizing psilocybin in a medical setting appealing to voters with negative preconceived notions of psychedelics in general. According to Backstrom, "because of the pandemic, a lot of Oregon ballot measures just died.” However, by the passing of the measure and despite the halting effects of the Coronavirus outbreak, volunteers had made cold-calls to over 60,000 voters, many of whom were open to voting “yes” on the ballot measure after volunteers were able to explain the research behind it and their own experience with it.

Some of these tenacious volunteers were not even Oregon residents, yet devoted large amounts of their time to see the measure through, despite the adverse effects that the COVID-19 pandemic had on the campaign. One of these volunteers was Danielle Isaacs, a dark-haired resident of Colorado with piercings speckled throughout her nose and cheeks.

“Somehow I saw one of Yes on 109’s posts and started following them on Instagram and then I saw opportunities to volunteer at the end of September,” said Isaacs of her origins with Yes on 109, “So I signed up for that and then just started volunteering every chance I got,” Isaacs says that, much like Backstrom and countless other volunteers for the campaign, her passion for psilocybin mushroom therapy rooted from personal experience. “I got such an avid interest in volunteering because psychedelics have really helped me,” she mentioned. “I know the power that they can have to help other people.” Isaacs got involved with the phone banks for the measure at the end of September 2020, when the legislation was beginning to gain the acclaim of psychedelic enthusiasts nationwide. Despite being unable to travel to Oregon to help collect petition signatures or knock on voters’ doors, she felt the best way to help rehabilitate psilocybin’s image as a healing tool instead of a harmful, addictive substance was to get involved with measure 109 as much as possible.

Isaacs is looking forward to the day when Colorado follows Oregon’s lead with a measure to legalize psilocybin therapy, which she believes will be relatively soon. “I do see something like this being a thing in Colorado and other states maybe in a few years,” she hypothesized, stating that, in small towns like hers, residents struggle with isolationism, often turning to addictive substances to find solace. As psilocybin has proven effective in resting substance addiction and Isaacs has experienced drug dependency treatment via psychedelic therapy, she is hopeful that the logic behind the measure will appeal to other state legislatures.

And she’s not the only one.

Daniel Brottman got involved with Yes on 109 from Rochester, New York. “One day I got an email saying ‘We did it! We’re on the ballot! We’re going to have a Zoom call celebration.’” he remembers, positioned pre painted on his bedroom wall, “I went and was just amazed and astounded by the energy that was there.” Brottman explained that he had experience with psilocybin mushrooms himself, though not entirely in a medicinal context. For Brottman, a sort of shift in connectedness to the self came with his psychedelic experiences, which he believes can make a significant difference in how others approach mental healthcare. “Our society is one of the only ones in human history that hasn’t had some sort of tradition of plant medicine usage because of it being outlawed,” he pointed out, “And I don’t think there is anywhere that [accessibility] to psilocybin and other plant medicines doesn’t have the potential to bring communities together.”

Studies have shown that Brottman’s conjecture is far from unreasonable. According to several studies conducted about psilocybin’s effects on community connectedness, there are significant improvements to mental health symptoms, addiction, treatment of individual trauma, as well as in addressing generational and racial trauma.

“We have transformed into the Healing Advocacy Fund,” Backstrom added, “It is a non-profit organization of which Sam Chapman is the ED (education director). Sam has been putting together a Health Equity Committee which will be made up of mostly BIPOC, rural community members, and mental healthcare professionals.” According to Backstrom, the committee will recommend specific regulations to OHA for The Psilocybin Mushrooms Services Program Initiative. These recommendations will play a significant role in the regulation, accessibility, and education of psilocybin therapy to traditionally underserved communities in the mental health field. As the measure continues through its incubation stage, this committee seems to be its most significant and current post-election development yet.

Rebecca Martinez, the co-founder of the Portland-based psychedelic research hub Fruiting Bodies, believes that the diversity in psychedelic healing and the medical field at large will be helped along with OHA and the OPAB addressing diversity and equity in psychedelic healthcare from the outset. She says that the Health Equity Committee is undoubtedly a step in the right direction, but legislators and activists can do more to make sure that diversity is a key factor in the Initiative in 2023 and beyond. “When it comes to representation, especially in Oregon, which is a predominantly white state, it has everything to do with being proactive,” Martinez said. “As we saw with the cannabis industry, if you do nothing [for diversity], then you kind of end up with a very one-dimensional group of applicants.” She offered many ways in which those working on measure 109 can ensure a diverse and inclusive psychedelic therapy industry, including licensure of practice, education, and, of course, representation in the state government.

“As of now, they have actually had to wait to announce the members of the Oregon Psilocybin Advisory Board, and that’s because they had a record number of applicants,” remarked Martinez, “They had over 250 people apply to be on that board, which is more than any other committee in Oregon’s history. Over 100 of those applicants applied for the seat of Member of the Public.”

However, looking ahead to the coming years of development for measure 109, Martinez believes that if community members keep up the avid interest in the measure push for equity, the Psilocybin Mushroom Services Program Initiative can prove to be a well-rounded, truly groundbreaking piece of legislation- then, and only then, can the measure live up to the high expectations and curiosity invested in it by people all across the nation.

https://webcache.googleusercontent....i-to-psychotherapy/+&cd=1&hl=en&ct=clnk&gl=us

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[mr peabody]

Psychedelic drug trials aim to break new ground in mental health

by Kezia Parkins | Clinical Trials Arena | 11 Jun 2021

Is the world about to experience a surge of medicinal psychedelics? We look at four breakthrough trials moving the needle.

The last few years have seen a renewed interest in psychedelics in clinical research, especially for mental and psychological illnesses. Subsequently, investment in psychedelic research is beginning to boom.

Psychedelic drugs and substances have had an interesting and meandering journey to get to where they are today.

Humanity’s connection to psychedelics for recreational and medicinal use dates back thousands of years. Western medicine only twigged to their potential to enhance psychotherapy in the 1950s and 1960s, particularly LSD and psilocybin, the active ingredient found in magic mushrooms.

Unfortunately, the “swinging 60s” and the rise of hippy counterculture saw the substances seep onto the streets and became popular drugs for recreational use. This led to them becoming stigmatised, politicised and in the 1970s, illegalised being declared Schedule I drugs in the US — substances with high abuse potential and no accepted medical use. Consequently, any promising research into their clinical uses came to a grinding halt.
The FDA’s landmark approval of Johnson & Johnson’s ketamine-derived nasal spray, Spravato for depression in March 2019 may have helped open the floodgates for other controversial drugs commonly used recreationally but with significant therapeutic potential.

Now a spate of new clinical trials looking into various psychedelic compounds in conjunction with intensive psychotherapy are underway or have been completed highlighting promising preliminary results.

These trials are underscoring a therapeutic one-two that is garnering increasing recognition – administering a mind-altering drug in combination with care from a trained therapist.

Many of the researchers and scientists carrying out studies in psychedelics believe they have the potential to ‘reset the brain’ thus helping it to break long-entrenched cycles and thought patterns associated with severe depression and addiction.

Psilocybin

Origin: Mushrooms found in Mexico

Indication: Major depressive disorder

Phase: Phase II

Sponsor: Imperial College London

In 2019 a modest group of researchers at Imperial College London established the Centre for Psychedelic Research, the world’s first dedicated centre for research into the mechanisms of action and clinical potential of psychedelic compounds.

The same year, a first-of-its-kind trial commenced out of the centre that saw a common antidepressant pitted against psilocybin to see if the substance could do a better job of battling depression.

The psilocybin formulation used in the trial was developed by UK company Compass Pathways, which received a breakthrough therapy designation from the FDA in 2018 for its earlier study of treatment-resistant depression.

The Phase II, double-blind, randomised, controlled Imperial trial involved 59 patients with long-standing, moderate-to-severe major depressive disorder (MDD). The study compared a psilocybin formulation against Lundbeck’s Lexapro (escitalopram), a selective serotonin reuptake inhibitor, over six weeks. 30 were assigned to the psilocybin group and 29 to the escitalopram group.

Patients were assigned in a 1:1 ratio to receive two separate doses of 25mg of psilocybin three weeks apart plus six weeks of daily placebo (psilocybin group) or two separate doses of 1mg of psilocybin three weeks apart plus six weeks of daily oral escitalopram (escitalopram group).

All of the patients in the study received intensive psychological support throughout.

The trial was run by Professor David Nutt, who was notoriously fired as the UK’s chief drugs advisor in 2009 after stating that alcohol and cigarettes were more dangerous than cannabis.

Nutt, who believes that psilocybin could revolutionise depression treatment by disrupting the areas of the brain that cause it, has said: “The criminalisation and banning of psychedelics is the worst censorship of research – not just medical research, but research – in the history of the world.”

The study found no statistically significant difference between the groups on depression scores using the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) scale, suggesting the two therapies worked as well as each other. However, the researchers also carried out other assessments of well-being, in which psilocybin appeared to come out on top.

This prompted critique from outside experts who claimed that the study design made it impossible to identify whether the psychedelic was actually more effective than escitalopram with regard to other measures of well-being.

“In hindsight I wish we’d made these other measures of well-being the primary outcome measure,” said Imperial Centre for Psychedelic Research head Dr Robin Carhart-Harris. “However the world — the Food and Drug Administration, the European Medicines Agency — doesn’t recognise those measures as valid.”

In a BBC documentary about the study participants, had positive things to say about their psilocybin experience, with one saying that the treatment meant she “felt like me again.”

MDMA

Origin: Psychoactive drug derived from safrole oil

Indication: Post-traumatic stress disorder (PTSD)

Phase: Phase III

Sponsor: MAPS

In a randomised, double-blind, placebo-controlled, multi-site Phase III clinical trial to test the efficacy and safety of MDMA-assisted therapy for the treatment of patients with severe PTSD, researchers reported that two-thirds (67 percent) of treated participants no longer qualified for a PTSD diagnosis after 18 weeks and three sessions.

The trial, funded and run by the nonprofit MAPS also found that 88% of people had a “meaningful reduction in symptoms”.

Talking therapy alone led to a significant improvement in 60%, and remission in 32% of people.

Patients in the study, the findings from which have been published in Nature Medicine, had been battling PTSD for an average of 14 years.

MDMA, popularly known as ecstasy, doesn’t induce the kind of vivid hallucinations associated with LSD or psilocybin, but rather boosts the brain’s levels of a number of neurotransmitters, including serotonin and dopamine, to create a sense of well-being and heightened empathy.

The trial’s researchers believe this might allow trauma survivors who face intrusive flashbacks to reflect on painful memories with less dread and self-judgement. “It gives you this fascinating ability toward self-compassion,” said the University of California, San Francisco neuroscientist and MAPS trial investigator Jennifer Mitchell.

MDMA was also found to be equally effective in participants with comorbidities that are often associated with treatment resistance.

MAPS hopes to confirm the results in an ongoing second Phase III trial and seek FDA approval for the therapy as early as 2023. The agency granted MDMA breakthrough designation in 2017, which comes with additional guidance during the trial process and an expedited review.​

Ibogaine​

Origin: Iboga shrub

Indication: Opioid addiction

Phase: Phase I/IIa

Sponsor: DemeRx and Atai Life Sciences

In March 2021, a joint venture between DemeRx and Atai Life Sciences was cleared by the UK Medicines and Healthcare products Regulatory Agency (MHRA) to start enrolment for a Phase I/IIa trial of ibogaine HCl (DMX-1002) in the treatment of opioid use disorder (OUD).

The opioid crisis is a critical unmet medical need, particularly in the US. In 2018 alone, 2.1 million Americans met the diagnostic criteria for OUD and 47,600 people died from opioid overdoses.

For those attempting to overcome opioid addiction, recovery is often thwarted by the current treatments available. Drugs like methadone or buprenorphine carry a high risk of abuse and come with side effects.

Ibogaine is a naturally occurring psychoactive compound isolated from a West African shrub called iboga, which has shown evidence of rapid and sustained efficacy in treating opioid use disorder (OUD).

The psychedelic has previously been marketed as a stimulant and antidepressant in France and studied elsewhere for addiction treatment including a large study led by DemeRx CEO Dr Deborah Mash in St. Kitts, West Indies.

“Not only were patients able to safely and successfully transition into sobriety, we found no evidence of additional abuse potential,” said Mash. “Given the limitation in currently available treatments, ibogaine represents an enormous leap forward for OUD sufferers.”

Phase I of the MHRA-approved trial is set to take place at the Manchester clinical unit of MAC Clinical Research (MAC), one of Europe’s largest independent clinical development organisations.
​

DMT​

Origin: Plants including the South American plant chacruna

Indication: Major depressive disorder

Clinical trial: Phase I/IIa

Sponsor: Small Pharma

Earlier this month, Small Pharma, a UK-based neuropharmaceutical company focused on psychedelic-assisted therapies, announced the expansion of its Phase I/IIa clinical trial for its lead product, SPL026, a N,N-dimethyltryptamine (DMT)-based treatment for MDD.

DMT is a powerful hallucinogenic found in numerous plants, including the South American shrub chacruna. When used recreationally or shamanistically it is brewed with the ayahuasca plant to make a tincture of the same name.

“Psychedelics have been shown to have therapeutic benefits in disorders such as depression, substance abuse and post-traumatic stress disorder,” said Small Pharma. “These so-called ‘internalizing disorders’ are characterized by debilitating flows of recurring negative thoughts.

“Clinical research suggests that DMT will break or disrupt the neuronal pathways that underlie these negative thought processes and by doing so, may facilitate the benefits of therapy given in combination with DMT. DMT-assisted therapy targets the root cause of depression and other ‘internalising’ conditions and has the potential to provide a treatment with rapid onset and a long duration of activity following treatment.”

The blinded, two-part Phase I/IIa clinical trial commenced in Q1 2021 and is being led by Hammersmith Medicines Research in London.

Phase I of the study aims to demonstrate the safety and tolerability of different dose levels of SPL026, a DMT fumarate, in ‘psychedelic-naïve subjects’ when compared to placebo. Phase IIa aims to affirm the patient proof-of-concept and will assess the efficacy, safety and tolerability of one versus two doses of SPL026, in combination with psychotherapy, in patients with MDD.

Efficacy will be evaluated using the Montgomery-Asberg Depression Rating Scale to measure the severity of depressive episodes.

Small Pharma has appointed MAC to expand the Phase IIa trial with an additional study site at Prescott, Liverpool, UK. This has helped bring the total number of participants in the trial to 42 and will mean that top-line results could be brought forward from the end of 2022 to the first half of 2022.

The firm’s CEO Peter Rands believes DMT will have an advantage over other psychedelic therapies as it can provide a short, powerful psychoactive experience lasting less than 30 minutes before being rapidly cleared from the bloodstream.

This could make it ideal for a short and focused therapy session skirting the need for intense monitoring by a healthcare professional, reducing costs.

“These characteristics allow DMT to stand out from other psychedelic compounds which typically generate a much longer psychoactive experience – the experience under psilocybin typically lasts six hours, LSD’s experience typically lasts 10 hours and ayahuasca 4-6 hours,” Rands said in an interview with pharmaphorum.

“We see this significant reduction in the duration of the dosing session as critical to the delivery of this treatment paradigm at scale in the future.”

The future of psychedelics in medicine

While these trials and others are a beacon of hope for the psychedelic therapy field and for patients in the grips of treatment-resistant depression and other disorders, there is a long way to go before such substances become market-ready.

Larger trials in far more diverse patient populations are needed and more need to be conducted head-to-head with existing and widely used treatments for mental illness.

For this, psychedelic research will require more investment and funding from public institutions and private investors, as well as clear regulatory pathways.

Regulator involvement will also be critical to increasing acceptance of psychedelic medicines as mainstream therapies and diminishing their reputation as “party drugs”. Now that the FDA has granted breakthrough therapy designation to treatments derived from both MDMA and psilocybin, the medicinal psychedelic field might just be poised to hit the pharma mainstream in the coming years.

Psychedelics: Psychedelic drug trials aim to break new ground in mental health

Is the world about to experience a surge of medicinal psychedelics? We look at four breakthrough trials moving the needle.

www.clinicaltrialsarena.com

 

[mr peabody]

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Opening up the future of psychedelic science

by Thomas Anderson & Rotem Petranker | The Conversation

Attempts to replicate classical scientific studies have been failing. These alarming failures have hit psychology, the life sciences and other fields, calling major findings into question. Scientists agree: questionable research practices are rife in many disciplines.

We are two psychology PhD students with experience researching mindfulness. We echo the scathing criticisms leveled against poorly designed studies within the field of mindfulness research.

As science is only trustworthy when consistent, we need to make sure future work can be replicated. As such, we have decided to spread the word about proper open scientific practice. This is especially important in the nascent interdisciplinary field of psychedelic science, in which we are now conducting research into the practise of “microdosing” substances like LSD and psilocybin.

There is a growing research literature suggesting psychedelics hold incredible promise for treating mental health ailments ranging from depression and anxiety to PTSD. But how do we know for sure?
​

The way forward for psychedelics is through “open science.” Researchers should pre-register their plans and share their data, as we have in our own research.

Science must be consistent

Science needs to have a strong foundation, but right now a lot of the research isn’t replicating. In 2015, the Reproducibility Project tried to replicate 100 high quality psychology findings. Only 39 of these findings were replicated — that’s less than half!

This phenomenon isn’t limited to psychology: findings from disciplines such as biology, medicine and chemistry can be hard to believe. For example, almost 500 authors were found guilty of misconduct by the Chinese government last year, several cancer research papers have been retracted recently and a recent report indicated that as much as 80 per cent of chemists have trouble replicating findings from the literature.

Several great pieces on The Conversation have tackled this issue so there is lots to review if replicability is new to you.

Psychedelic research is an interdisciplinary field combining psychology, biology and medicine and so is an especially important field in which to implement “open science.”

Open science = rigorous science

For statistics in science to work properly, scientists need to guarantee that what they have studied is no more and no less than what they intended to study.

Instead of hiding inconvenient results or adding unplanned research conditions, scientists can use open science to demonstrate their integrity. Open science involves pre-registering hypotheses before doing research, and publishing the entire data set once the research is done.

Pre-registration happens online. The content of the registration is locked and time stamped, then kept confidential until a set date, when it is released for the public to see. This is done so that the researcher can show they did exactly what they planned to do, which is how we all learned we are supposed to do science. Pre-registration is not even difficult, but researchers need to learn how to do it and adjust.

Once the study has been published, the data set can be made public. This way, the entire scientific community can examine the data, serving at least two purposes. First, the scientific community can verify that the data supports the conclusions made in the study, ensuring no mistakes were made. Second, other scientists can explore for new patterns in the data to create new hypotheses for new studies, moving science forward faster.

Making the data public makes scientists publicly accountable, and is good for the scientific community at large.

Cooperation over competition

So far, most psychedelic research has not been pre-registered, which means it should be considered exploratory and, unfortunately, inconclusive. Some findings may have been by chance rather than clearly caused by the substances used, and these findings need to be replicated by independent labs to ensure they hold up.

A recent call for “Cooperation Over Competition” has been made, but its impact remains to be seen. For now, we take the results on psychedelics that scientists have found on faith.

Pre-registration is the only way to ensure psychedelic science is conducted with a high level of integrity. Psychedelic science is in its infancy, much as mindfulness research was some few decades ago. We must learn from past mistakes if we do not wish to see the same harsh criticisms levelled upon this field in the future.

This will improve and maintain public trust in the scientific endeavour, especially important for these storied substances. As public consumers of science, we should all be critical of new research and remember the Sagan Standard: “Extraordinary claims require extraordinary evidence.”

Opening up the future of psychedelic science

To know the real promise of psychedelic substances like LSD, mushrooms and MDMA, researchers must embrace the principles and practise of ‘open science.’

theconversation.com

 

[mr peabody]

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The future of psychedelic science: What the next decade holds

by Rich Haridy | NEW ATLAS | 26Dec 2019

The last decade has been inarguably incredible for the field of psychedelic science. The term renaissance is hyperbolically thrown around a lot these days but in this context it is perfectly apt. Moving from the fringes of the research world and shaking off years of baggage from illicit recreational circles, scientists have made startling progress in legitimizing the medical potential of these drugs.

With both MDMA and psilocybin on the precipice of approvals as mainstream medicines, and several leading universities opening dedicated psychedelic research facilities, the story of the last 10 years has been one of profound breakthroughs. So, as we stand on the precipice of a new decade, it's worth pausing for a moment and looking forward to investigate what the 2020s may hold in this rapidly accelerating field.

New Atlas spoke to several leading psychedelic researchers to get their thoughts on three big future-forward questions. Where will psychedelic science be in 2030, what is the biggest hurdle psychedelic researchers will face in the 2020s, and what is the most interesting psychedelic research topic that has yet to be fully explored?

MAPS

Founded by Rick Doblin in 1986, MAPS ostensibly began as a response to the DEA criminalizing MDMA, a drug Doblin viewed as holding remarkable potential as an aid to psychotherapy. For the next 30+ years MAPS has been at the forefront of the movement to legitimize psychedelic research and science.

With MAPS on the verge of culminating decades of work with an FDA approval for MDMA as a PTSD treatment the organization’s Director of Strategic Communication Brad Burge offers us an exciting insight into what the next 10 years hold for the field of psychedelic science.

The next 10 years?

Within 10 years we are likely to have multiple psychedelic-assisted therapies approved in the US, Europe, and in many countries around the world for the treatment of various mental health conditions. As new success stories from treatment with psychedelic therapy continue to emerge, and new scientific evidence continues to be collected from ongoing clinical trials and neuropsychopharmacology research, many more patients will be asking for these treatments. We’ll see multiple forms of treatment centers emerge, including psychiatric hospitals as well as privately owned clinics and independent practitioners. Psychedelic therapy is on track to be the next major breakthrough in mental health care.

The most interesting “yet to be answered” research question?

MAPS is now in the planning phase for Phase 2 clinical trials of ibogaine-assisted therapy for the treatment of opioid addiction. Like PTSD, opioid addiction is a national and global epidemic, and I’m excited that our next major focus will be on developing a way of treating it that doesn’t rely on addiction replacement therapy. It’s also inspiring to me that pharmaceutical clinical trials for ibogaine-assisted therapy could help address an epidemic caused in large part by the for-profit pharmaceutical industry.

The biggest challenge still facing the psychedelic science community?

Once MDMA-assisted psychotherapy is approved for the treatment of PTSD, the key challenge will be getting it to the patients who need it. MAPS has already begun to undertake the massive project of certifying hundreds, and eventually thousands and tens of thousands, of therapeutic practitioners in the practice of MDMA-assisted psychotherapy. As increasing numbers of clinicians start delivering the treatment, ensuring adequate training in therapeutic principles, ethics, and other vital aspects of delivering MDMA-assisted psychotherapy will be crucial.

Another challenge moving forward is accessibility, including insurance coverage. This is especially a challenge because insurance companies tend to resist paying for psychotherapy. Psychedelic-assisted therapy is a new form of psychotherapy that uses a psychedelic drug to enhance its effects. As such, educating insurance providers and health policy regulators about psychedelic-assisted therapy is vital for ensuring as wide accessibility as possible for patients seeking treatment with government-approved psychedelic therapies

Dr Ben Sessa

After training as an adolescent and child psychiatrist, Ben Sessa became a key figure in the psychedelic science renaissance over the past 20 years in the United Kingdom. He has played a major role in the progression of MDMA-assisted psychotherapy research, penned dozens of journal articles discussing the integration of psychiatry and psychedelics, and co-founded Breaking Convention – one of the world’s largest academic conferences for psychedelic medicine.

The next 10 years?

Plans are underway (by MAPS and Compass Pathways, respectively) to see MDMA and psilocybin approved as licensed medicines in the US (under FDA) ... by late 2022 – possibly sooner. So by 2030 these will be well-established medicines being prescribed by UK doctors as part of approved therapy schemes. I also expect these medicines to be free on the NHS by 2030, if not earlier.

The most interesting “yet to be answered” research question?

Using cannabis medicine and psychedelic-assisted therapies to dismantle the old-fashioned (and erroneous) system of psychiatric categorical diagnoses. We will hopefully see the end of long-term daily maintenance medications with SSRI (Selective Serotonin Reuptake Inhibitor) and instead see patients formulating their own bespoke, individualized care plans according to their unique profile of psychosocial functioning and feelings.

The biggest challenge still facing the psychedelic science community?

The biggest challenge has always been – and will always be – money. Ninety-nine percent of human psychopharmacology research comes from the Pharma industry, who have trillions of pounds to spend on researching new treatments. All psychedelic research has come from charitable donations and philanthropy. We are starting to see investors getting involved, which [in my opinion] is a good thing, as this will help overcome the financial barriers that have held back psychedelic research for so long up till now.

​

Dr. Natalie Gukasyan

Natalie Gukasyan is a psychiatrist and research fellow at Johns Hopkins University. Her work is conducted at Johns Hopkins' Center for Psychedelic and Consciousness Research, and she focuses on psilocybin-assisted psychotherapy for mood, addictive, and eating disorders. Her latest project involves a landmark clinical trial exploring the safety and efficacy of psilocybin in persons with chronic anorexia nervosa.

The next 10 years?

If we are able to demonstrate efficacy and safety in large phase 2 and 3 studies, this could lead to compounds like MDMA and psilocybin being rescheduled and approved for clinical use. Ten years from now we may see the proliferation of specialized clinics and perhaps later, integration of specialized services into existing healthcare infrastructure. Wider use would allow us to get more clinical data and get a better understanding of how to mitigate risks and maximize benefits based on individual characteristics and circumstances.

The most interesting “yet to be answered” research question?

There are many clinically salient questions that are unanswered – e.g. efficacy and safety of microdosing, or using other psychedelic compounds with shorter duration of action like 5-MeO-DMT. There are also more practical pharmacologic questions – how long does someone using SSRI’s really need to be off of those medications before taking a drug like psilocybin?

The biggest challenge still facing the psychedelic science community?

Phase 2 and 3 studies will require massive amounts of effort and money, but this would be a necessary step in getting these drugs rescheduled and available for clinical use. Ultimately, however, rescheduling is a legislative issue and can depend on political factors. Once that hurdle is cleared, scaling the treatment and making it affordable and accessible will also be a huge challenge. We will likely have to explore alternative models of delivering care that are different from the usual model presented in clinical trials.
​

The future of psychedelic science: What the next decade holds

The last decade has been inarguably incredible for the field of psychedelic science. The term renaissance is hyperbolically thrown around a lot these days but in this context it is perfectly apt. Moving from the fringes of the research world and shaking off years of baggage from illicit…

newatlas.com

 

[mr peabody]

Henry Nasrallah, MD

How psychedelics morphed into novel treatments*

Mind-altering drugs, once considered dangerous, are being investigated for treating depression, PTSD, anxiety, and other psychiatric illnesses.

by Henry Nasrallah, MD | Current Psychiatry

In medicine we must always expect the unexpected. Medicine is replete with paradoxes, where poisons become cures. Snake venom is deadly but is being used to treat some cancers, because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flash-light, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus. Vaccines are an excellent example of how deadly pathogens can be trans-formed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded psychedelics as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining. Consider the following transformations of various psychedelics and psychedelics—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

LSD

LSD was used extensively for treating mood dis-orders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncon-trolled—concluded that approximately 80% of patients improved, according to the treating physicians. However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects. LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards. In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust. Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects sub-side within 3 days.

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects. Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants. Other emerging uses of both psilocybin and LSD are in treating addictions8 where psychiatry is desperately looking for innovative new therapies.

MDMA

MDMA is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for post-traumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months. Other studies showed no effects. Despite persistent skepticisms by many, MAPS is investing millions of dollars into studying MDMA for PTSD in several countries. One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their pro-found effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue. MDMA also is being studied for treating social anxiety in adults with autism.

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spot-light as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies. This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.Published through an educational partnership with Saint Louis University

Cannabis

Last, but certainly not least, is cannabis, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of cannabis, studies have pointed to the myriad medical uses of Cannabis. An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on cannabis research. Some of the medical applications of cannabis include:

•Psychiatry (anxiety, PTSD)
•Neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
•Oncology (nausea and pain of che-motherapy, reduction of metastasis)
•Ophthalmology (decrease of intraocular pressure in glaucoma)
•Autoimmune Disorders (rheumatoid arthritis, Crohn’s disease, lupus). However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages! Could our field have suffered from a blind eye to the benefits of these psychedelics and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their undiagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

*From the article here :

https://cdn.mdedge.com/files/s3fs-public/CP01601019.PDF

 

[mr peabody]

Psychedelics: A new fountain of youth?

by Kali Carrigan, MA | Psychedelic Science Review | 4 Jun 2021

LSD and psilocybin have been associated with significant positive changes in clinical measures of depression, anxiety, and psychiatric disorders such as OCD and addiction. An emerging property of psychedelics, however, is their anti-inflammatory potential. Recent studies have found evidence for the role of the 5-HT2A receptor in the inflammatory response, showing that activation of this receptor modulates a potent anti-inflammatory response in animal models.

More recently, psychedelics have also been found to act on several cell signalling pathways associated with genetic aging, such as the mTOR and BDNF pathways. In a study released this year, researchers found that lifetime use of classic psychedelics such as psilocybin and LSD was correlated with significantly greater overall physical health, and lower odds of having a heart condition and/or cancer within the last twelve months. But, how robust is this correlation? Could psychedelics be helping us live longer and healthier lives?

The 5-HT2A receptor and inflammation

Low-grade chronic inflammation has been put forth as one of the primary contributors to the development of age-related diseases. This is best known as ‘inflammaging’, and it is the result of an excessive immune reaction to specific stressors which worsen over the life course. Psychedelics have been found to elicit strong anti-inflammatory properties through their action on the 5HT2A receptor, and have been posited as promising treatments against inflammatory disorders.

In a landmark study carried out in 2013, researchers showed that selective activation of the serotonin 5-HT2A receptor is able to block the effects of tumour necrosis factor-alpha (TNF-α), which plays a key role in inflammation. Charles Nichols, a proponent of this theory, has suggested that psychedelics may in fact be a powerful and effective treatment for age-related diseases such as atherosclerosis and inflammatory bowel disease. His company, Eleusis, intends to carry out preclinical and clinical trials in the coming years on the anti-inflammatory potential of psychedelics, which they are seeking to develop outside of their perceptual and consciousness-altering properties.

The ‘Psilocybin-Telomere Hypothesis’

Telomeres, the small ‘caps’ at the end of chromosomes, have been implicated as key markers of genetic aging since the 1980s. Telomere shortening caused by the aging process has been linked to premature cell senescence, genetic instability, and an impaired DNA damage response, leading to a global decline in function as we get older. Interestingly, telomeres have been found to function as ‘psychobiomarkers,’ that is, they are in part regulated by psychological factors such as depression and anxiety.

A recent meta-analysis of 38 studies investigating the relationship between telomere length and depression found a significant inverse correlation between these two factors. In 2020, Christopher B. Germann proposed that psilocybin could be having a direct positive impact on leukocyte telomere length, particularly in the brain. His theory, which he coined the ‘psilocybin-telomere hypothesis’ was based on deductive logic: if depression shortens telomeres and psilocybin reduces depression, then psilocybin must have an effect on telomere length and therefore genetic aging.

mTOR, BDNF, and Synaptic Plasticity

Recently, serotonergic psychedelics have also been found to elicit profound changes in neuroplasticity through their action on the mTOR (mammalian target of rapamycin) and BDNF (brain-derived neurotrophic factor) cellular pathways. Both mTOR and BDNF have been widely associated with genetic aging, in particular age-related neurodegeneration. In four separate peer-reviewed studies, the anti-depressant effects of ketamine, ayahuasca, LSD, and psilocybin were strongly associated with their effects on these signalling pathways.

While the mechanism of action of psychedelics on these aging-related pathways is not yet fully understood, it has been thought to involve the BDNF-enhanced delivery of AMPA to the synapse. Researchers such as Robin Carhart-Harris have suggested that this action could explain the enhancement of neural plasticity elicited by psychedelics, as well as the phenomenological feelings of “resetting” following a psychedelic experience.

Conclusion

Through their action on inflammatory pathways as well as those classically associated with genetic aging such as telomere length and the activation of the mTOR and BDNF pathways, serotonergic psychedelics seem to do more than just change consciousness. Evidence is mounting for the possible use of psychedelics in slowing down genetic aging and cognitive decline over the life course. It is still too early to say whether anti-aging therapies are a possible future use of psychedelics, but the science seems to be pointing in that direction.

Psychedelics: A New Fountain of Youth?

Psychedelics may help us add healthy years to our lives.

psychedelicreview.com

 

[mr peabody]

Psychedelic drugs moving from the fringes of medicine to the mainstream

by Joshua Cohen

Psychedelic agents are experiencing a veritable renaissance. And this time not as illicit mind-expanding drugs that helped give shape to the 1960s counterculture. In recent years a slew of psychedelic agents have filled the drug development pipeline. These therapeutics are being investigated for treating conditions, such as major depressive disorder, severe anxiety, and substance abuse. Psychedelic therapeutics have moved from the fringes of medicine to the mainstream.

In May, the journal Nature Medicine published findings from a study on MDMA - Methylenedioxymethamphetamine - commonly known as Ecstasy or Molly. The first Phase 3 clinical trial conducted with psychedelic-assisted therapy found that MDMA combined with psychological counseling yielded “marked relief to patients with severe post-traumatic stress disorder.”

In April, a study published in the New England Journal of Medicine highlighted the benefits of treating depression with psilocybin, the psychoactive ingredient in magic mushrooms, have excited scientists, psychotherapists and entrepreneurs in the rapidly expanding field of psychedelic medicine. Other studies suggest “substantial rapid and enduring” antidepressant effects of psilocybin-assisted therapy among patients with major depressive disorder. The Food and Drug Administration (FDA) granted psilocybin “breakthrough” therapy designation.

And, esketamine was approved by the FDA on March 5th, 2019, for treatment-resistant depression. It is sold under the trade name, Spravato. Esketamine became the first FDA-approved psychedelic treatment for a psychiatric disorder. In August of last year, the FDA extended its approval for esketamine to adults with major depressive disorder with acute suicidal ideation or behavior.

In a disease area such as mental health, with a significant amount of unmet need, any increase in promising treatment options is welcome. Major depressive disorder affects approximately 17 million Americans, many of whom currently suffer from a lack of adequate treatment alternatives. However, there are possible pitfalls associated with each of the aforementioned drugs where the precautionary principle may apply. In each instance, risks of abuse and diversion must be considered.

There is the potential for abuse and possible long-term negative effects related to MDMA, an amphetamine derivative. Research hasn’t definitively answered whether MDMA is addictive, although data suggest that regular MDMA use yields adaptations in the serotonin and dopamine pathways in the brain and central nervous system that may be connected to substance use disorder as well as increased impulsivity. Clearly this is an important factor to consider as medical uses for MDMA are being pursued.

In the case of psilocybin, in the span of a couple of years, the drug has gone from being a completely prohibited Schedule I drug, defined by the Drug Enforcement Administration as a controlled substance having “no currently accepted medical use and a high potential for abuse,” to a what some researchers recommend should be a Schedule IV controlled substance drug with a relatively low potential for abuse.

Yet, psilocybin is considered to have abuse potential. While advocates assert that psilocybin is not addictive, chronic abuse and misuse can lead to hallucinogen use disorder.

The FDA is the focal point for abuse potential assessment, and works with sponsors of agents with possible abuse potential to determine the studies required to establish approval endpoints, scheduling recommendations, and all aspects of labeling. Psilocybin has not yet been examined in an abuse potential study that would meet the criteria recommended by the FDA in its 2017 Guidance: Assessment of the Abuse Potential of Drugs.

Furthermore, abuse and misuse are not the only problems that require investigating. However rare the risks appear to be from initial reports, possible adverse events must be looked into thoroughly, particularly since clinical trial and real-world settings are vastly different. Persistent use of psilocybin may lead to long-term psychosis, alter a person’s personality and perception of reality, and produce hallucinations.

Dr. Bogenschutz, a professor of psychiatry at New York University, said that until now the majority of clinical studies on psilocybin have been conducted with relatively small numbers of individuals in clinical settings designed to exclude those with schizophrenia and other serious mental problems. It is precisely these subgroups that could be predisposed to psychotic episodes, exacerbated by possibly psychosis-inducing psilocybin.

And then there’s the case of esketamine, which is the S-enantiomer of ketamine, a similar (in molecular structure) but more potent agent than ketamine. The FDA label for esketamine includes a black box warning of the potential for misuse.

The experience with off-label use of ketamine for clinical depression is a sobering reminder of the importance of close monitoring for the purpose of preventing abuse and misuse from occurring. As noted in several clinical studies, ketamine “drug-seeking behavior has appeared as a clinical issue, with some patients shopping infusion clinics to obtain repeated injections for mood elevation.” In 2017, the American Psychiatric Association issued a consensus statement on ketamine for mood disorders: “Considering the known potential for abuse of ketamine and recent reports of abuse of prescribed ketamine for the treatment of depression, clinicians should be vigilant about assessing the potential for patients to develop ketamine use disorder.”

Classified as a Schedule III substance, esketamine’s safety profile based on real-world data includes possible dissociation, sedation, and suicidal ideation. Mark Horowitz of University College London, asserted that “what the sponsor demonstrated very clearly in the trials that they’ve done is that esketamine gets you a bit high for a few hours and has little effect on depression scores at 4 weeks.” Horowitz maintains that esketamine is “an ineffective medication. On top of that, it’s also a reasonably dangerous medication.”

Ignoring or downplaying possible downsides or risk factors isn’t going to make these issues go away. The experience with prescription opioids and other drugs, such as benzodiazepines, should give pause. Despite the benzodiazepine clonazepam being the most commonly diverted pharmaceutical in the U.S., it remains the drug most prescribed by psychiatrists to Medicare beneficiaries.

Regulators are proactively establishing a strict set of protocols for psychedelic medications. Several regulatory barriers have already been erected for the approved drug esketamine. Presumably, a similar set of restrictions would be put in place for MDMA and psilocybin. With respect to psilocybin, it appears that only licensed therapists and manufacturers will be allowed to grow the mushrooms or extract psilocybin from them, or to synthetically produce the drug, set up a psilocybin therapy center or provide therapy. Importantly, individuals being treated with the drug may only ingest it at a licensed facility with a certified therapist present.

These safeguards will help, along with systematically implemented post-marketing surveillance plans. Still, regulators and treatment providers will need to work out safe ways of administering these powerful substances in the real world, which will be different from the highly circumscribed and controlled conditions of clinical trials.
​

 

[mr peabody]

How psychedelics are entering the mainstream

by Annie Lennon | Psychology Today | 15 Sep 2020

New treatment models aim to make psychedelics increasingly common.

Signs of progress in the field of psychedelics are easy to come by. You needn't look far to notice the increasingly robust research emerging on their ability to aid multiple mental health conditions. And as such, many are starting to wonder where they can access the treatment.

Psychedelics have shown particular promise in treating depression, with psilocybin (the psychoactive compound in magic mushrooms) having achieved "Breakthrough Therapy" status by the FDA for the condition. Despite this, though, a standardized treatment model for delivering psilocybin-assisted therapy outside of research settings does not currently exist.

That means, for the most part, people can only legally access the treatment by qualifying for a clinical trial, and there is no way for patients to continue the therapy afterward. This leaves them without proper support.

"It's difficult seeing people in our studies who are really helped by psychedelic-assisted psychotherapy only to be desperate for it again so they can continue treatment," says Dr. Rosalind Watts, the former clinical lead of the Psilocybin for Depression Study at the Centre for Psychedelic Research at Imperial College London.

"I'm in contact with someone from the first study who, five years later, is still contacting me saying he really needs another session but doesn't know where to go as he can't access this care anywhere."

Watts has first-hand experience treating patients with psilocybin as a session guide in two studies investigating the compound on depression. She has also conducted research on how participants regard the treatment. From her work, she now feels the therapy is both safe and promising enough to become more widely available to those who meet the same inclusion criteria used in the studies.



As such, she has joined Synthesis, a legal psychedelic retreat center in the Netherlands. There, she will aid the center in developing a long-term therapy program that includes sessions with psilocybin-containing truffles—a pre-developmental form of mushrooms.

But creating a treatment model for psychedelics from scratch is no easy feat. Due to the decades-long stigma against psychedelics, Synthesis and other centers offering psychedelic treatments including Ember Health and Clear Sky Recovery, have no longstanding "manual of best practice" to follow.

Moreover, current models of psychedelic-assisted psychotherapy are prohibitively expensive. So far, studies investigating the therapy for depression require each patient to be accompanied by two therapists for a whole day, not counting additional hours for regular psychotherapy to integrate their experiences. Although shown to be effective, due to its high cost, the treatment in its current state is unlikely to become mainstream.

To change this, different centers are experimenting with different models for psychedelic-assisted psychotherapy.

New York-based Ember Health, for example, a clinic specializing in treating depression with ketamine, works with patients and their care teams to develop treatment plans involving intravenous infusions of the drug for 40 minutes, followed by 20 minutes of resting time before discharge.

Patients are advised to have four infusions over two weeks as a foundation, and then "top-ups" according to their specific needs. Taking an hour per session, Ember Health's model minimizes costs and makes it easier to integrate their treatment with existing treatments and everyday life.

Synthesis, on the other hand, has a group approach. In their therapy program, each attendee receives six weeks of preparation therapy, leading up to a week-long truffle-assisted group therapy retreat. Following aftercare and follow-up, attendees then begin a 12-month online integration program.

Although more resource-heavy than Ember Health's offering, Synthesis is still able to keep costs lower than the model used in the Imperial studies as each participant has just one personal facilitator throughout their psilocybin experience, as opposed to two.

Regardless of the model though, for now, psychedelic-assisted therapy is still prohibitively expensive to most and generally not covered by health insurance. Prices generally range from hundreds of dollars per session to thousands of dollars per treatment plan.

Given that many in the field are motivated by widening access to psychedelic medicine, these cost barriers are far from ideal. But at the same time, many recognize that it may be a necessary evil for now. Watts, for example, likens the development of psychedelic treatment models to that of the Tesla car: starting by targeting high-end consumers to cover the costs of developing a proper, scalable model that is both accessible and affordable to the masses.

But this doesn't mean that those with less financial means will not be able to gain access to psychedelic-assisted psychotherapy. Ember Health, for example, has committed to providing reduced infusion fees for up to 20% of their patients at any given time. Meanwhile, Synthesis has opened a scholarship fund, which has so far enabled 16 people who took part in the Imperial studies to enroll in their program.

As more people receive various forms of psychedelic-assisted therapy, those at the forefront of the treatment hope that healthcare providers will soon start to understand its value and eventually refer people for the treatment. Ultimately, they hope to see psychedelic-assisted therapy become a gold-standard treatment option, and for it to be covered by insurance companies.

For this to happen, though, more work is needed from researchers, healthcare providers, and retreat centers alike to develop effective and scalable models for the treatment. When asked what the most important aspect of this psychedelic-assisted therapy model is, Watts answered with one word: trust.

"The most important thing in psychedelic therapy is that people trust you, trust the medicine you're providing, and trust the team that they're working with," says Watts. "This then allows them to trust themselves, something that is crucial going in, especially as psilocybin experiences can be so incredibly intense."

Despite the hurdles, there is a widespread sentiment in the field of psychedelics that it's just a matter of time before they become mainstream. In this sense, the "what" has already been established. What's left now is the "how." And with the research behind these drugs gaining more acclaim, it is now up to treatment providers to play their part in seeing them leave novelty and enter convention.

How Psychedelics Are Entering the Mainstream

New treatment models aim to make psychedelics increasingly common.

www.psychologytoday.com

 

[mr peabody]

Opportunities in Psychedelic Medicine: A crash course*

by Joshua Genuth | Green Entrepreneur

Anyone within shouting distance of psychedelic culture knows that there are big things happening these days in mental health and addiction therapies using psychedelic medicines. After 40 plus years of federal and state clampdown on any ingestible once perceived as having no merit beyond social upheaval and a threshold into irreversible madness, psychedelics are back, baby.

Pardoning outlawed substances

Today’s stone-cold sober research into the benefits of compounds including psilocybin mushrooms, LSD, ibogaine, MDMA, and ketamine is picking up right where it left off, with clinical results many times more successful than any previous medication or therapeutic method.

And it’s being met with great public fanfare: renowned author Michael Pollan’s New York Times bestseller, How to Change your Mind, swept the groundbreaking modern scientific research into the public dialogue. Amazingly, even the feds are backing down from their traditional posture of prohibition. Last year, psilocybin was designated a ‘breakthrough therapy’ for severe depression by the FDA.

This old/new wave of treatment options for depression, anxiety, addiction, PTSD, and other mental health issues could not be materializing at a more opportune time. The coronavirus has triggered spikes in depression and substance abuse across the world, and suicide rates among war veterans and other trauma survivors are apalling and getting worse.

Real hope for the hopeless

Psychedelic medicines offer help in exactly the areas where conventional treatments have most resoundingly failed. Psychedelics are inexpensive to produce, non-addicting, highly effective with treatment-resistant patients, generally require only a few sessions for substantial results, and carry only minuscule potential side effects. Study after study by teams at prestigious institutions like Johns Hopkins University and New York University have demonstrated that something in the deeply impactful and highly personalized therapeutic psychedelic experience just works, even in situations where years or decades of traditional treatments have not.

Recent psilocybin and MDMA trials for PTSD have even been conducted with US combat and law enforcement veterans - not an especially trippy demographic - with remarkable success. Veterans, many struggling with trauma and suicidal thoughts, have also discovered breakthrough positive realignments following therapeutic ayahuasca ceremonies. Broader clinical trials with a range of psychoactive compounds are still forthcoming for cocaine addiction, eating disorders, end of life anxiety, and much more.

The potential these compounds have to upend conventional treatment methods is, on a market level, considered a real challenge to a pharmaceutical industry that relies on long-term patient use of chemical medicines as a cornerstone of its business model. As such, a private industry ecosystem is steadily sprouting up around the psychedelic medicinal sector. Startups and other organizations are entering the space with contributions including medicinal supply, data-driven treatment platforms, legal and legislative work, therapeutic clinics, public education, and much more. Canada-based Novamind, for example, is laying the groundwork for psychedelic treatment clinics across the globe, while Entheon Biomedical focuses on researching and manufacturing psychoactive drugs for treating substance addiction in a therapeutic setting.

Psychedelic-assisted treatments are already changing the lives of individuals the world over, and the only question of full public access is not ‘if’, but ‘when.’ The answer is based largely on governmental restrictions, particularly in the United States. Currently, there are many unknowns in how and when the federal government will reschedule these compounds. Of course, the American national apparatus is a bit distracted as of this writing, so the coming federal policies are as yet unknown. Regardless, the medicinal psychedelic movement has enough science, research, and clinical results behind it to be taken seriously by even the most conservative governmental body.

Given the legitimate hype being generated by these exciting medicines, a crucial step in their real-world implementation is connecting the players working on different angles, sharing knowledge, and educating the public. Despite the current pandemic limitations, the industry is generating events and conferences aimed at information sharing and multidisciplinary coordination.

*From the article here :

A Crash Course On Opportunities In Psychedelic Medicine

PsyTech's free virtual summit gives participants insight into the medicinal movement.

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[mr peabody]

How psychedelics are returning to the world of medicine

by Matthias von Hein | DW | 2 Oct 2021

Millions of people in Germany have been diagnosed with depression. Researchers believe that drugs such as LSD and psilocybin can offer an effective treatment. They could also bring big profits.

On July 13, there was a rainy sky above the southern German city of Mannheim. But, despite the uninspiring weather, it was a day of hope for millions of people with depression — because the first patients of a research project run by the Central Institute of Mental Health were scheduled to have a psychedelic experience.

They wore a blindfolds and headphones that played music and were accompanied by two therapists. The hallucinogen used for the inner journey is called psilocybin.

This active ingredient was isolated about 60 years ago. It gives the magic mushrooms their "magic" — i.e., their mind-altering effect. And it has been banned almost worldwide, including in Germany, for over half a century.

Even for the Mannheim researchers, "obtaining the substance has proven to be the highest hurdle." That's according to researcher and psychiatry professor Gerhard Gründer.

"There are not that many manufacturers in the world from whom you can obtain such a substance in the required quality. It was a long and laborious process," he said.

But that laborious process is becoming more common. Hallucinogenic trips have long ceased to be solely the recreational pastime of hippies. A growing number of scientific studies point to the potential of psilocybin-assisted therapy for treating depressed patients — even those for whom other therapies have been exhausted. The Mannheim study, with a total of 144 patients, is now large enough that Gründer "expects statistically robust conclusions."

Depression is a widespread condition

According to estimates by the World Health Organization, about 300 million people worldwide live with depression. In Germany, that number is an estimated 5 million, and the Health Ministry has referred to it as a "widespread disease."

A conservative estimate is that around one in five patients cannot be helped with conventional treatment methods. "There is a huge need," Gründer said, adding that his institute is almost overrun with inquiries from patients.

In conventional therapies, patients are treated with daily doses of antidepressants. The new approach is fundamentally different.

"Here, it's a matter of taking this substance once or twice," Gründer said. "This is a very disruptive therapy that becomes embedded in a psychotherapeutic program."

Gründer believes that there is a huge need for unconventional therapy

Subjects in earlier studies reported life-changing experiences and significantly improved mental states, and were even able to stop taking their antidepressants, often a state that lasted for many months after the healing trip. The prospect of being able to significantly improve the condition of severely depressed people with just a few psychedelic sessions is worth over €2 million ($2.3 million) in funding to the ministry of education and research.

The fact that public money is now also flowing into research with psilocybin in Germany shows that psychedelic research is slowly edging from the fringes into the medical mainstream.

Psychedelic substances have returned to where they once stood in the 1950s and '60s — to the center of psychiatric, medical and psychological research.

International meeting of experts in Berlin

This could be seen in mid-September in Berlin, when the Insight 2021 conference took place, organized by the Mind Foundation. According to its website, the foundation advocates the "evidence-based, safe and legal use of psychedelic experience in medicine and society." The venue for the meeting of the center of international psychedelics research is the Berlin Charite, one of Germany's most prestigious medical institutions.

For four days, attendees discussed neurological processes, compared the effects of LSD, psilocybin and other drugs with diagrams, and presented the state of research in a wide variety of fields. Even an employee of the German drug approval authority, the federal authority for drugs and medical devices, was there.

"We managed to destigmatize the topic; a discourse has emerged," Mind Foundation co-founder Andrea Jungaberle said in summary. "How this discourse will affect day-to-day medical business remains to be seen."

Experts are already enthusiastic. "How ecstasy and psilocybin are shaking up psychiatry" a headline of the science magazine Nature gushed at the beginning of the year.

Psilocybin on the stock market

A growing number of companies are also keen. If they had their way, psilocybin, the ecstasy active ingredient MDMA and other substances would soon be used across the board to treat depression, addiction, and an array of other diseases. At least, that is the goal of the biotech holding company ATAI Life Sciences, owned by German investor Christian Angermayer.

Angermayer has discussed his own psilocybin experiences in German media, including newspapers Handelsblatt and Wirtschaftswoche — and this summer he took his company public in New York. Just three years after its founding, the psychedelic holding is already worth over $2 billion.

ATAI's holdings include Compass Pathways, a British company that has developed its own synthetic psilocybin. Compass Pathways is currently conducting a phase 2 trial with the drug involving more than 200 patients at 22 locations in 10 countries, currently the largest psilocybin clinical trial in the world. The company, which is also listed on the Nasdaq in New York, has been valued at over $1 billion after only five years in existence.

The Berlin Registry of the Mind Foundation shows that the "trip therapy boom" has allowed an entire industry to flourish. It lists about 130 companies in the psychedelic industry, from A Whole New High, which offers psilocybin retreats in the Netherlands, to Wavepaths, a specialist for the right sound via headphones for an inward journey.

Even Andrea Jungaberle is not entirely comfortable with the rapid development. "Our best friend and our biggest enemy is the hype," she states soberly, "promoting an appropriate approach between demonization and transfiguration."

Swiss psychotherapist Peter Gasser, who has been working with LSD and MDMA for 30 years, shares this assessment.

"This pace almost scares me," he said. "This scaling up of small niche treatments: Just a few patients per the study, now you're already thinking in terms of millions." Gasser fears that the quality of treatment could suffer "because it's seen as too technological or too schematic."

How psychedelics are returning to the world of medicine | DW | 02.10.2021

Millions of people in Germany have been diagnosed with depression. Researchers believe that drugs such as LSD and psilocybin can offer an effective treatment. They could also bring big profits.

www.dw.com

 

[mr peabody]

​

Envisioning a Psychedelic Future for Psychiatric Treatment

by Sam Wood | Medical Xpress | 17 Feb 2021

Jason Wallach has a vision. He sees Philadelphia becoming a center for psychedelic studies. From his laboratory at the University of the Sciences, Wallach is leading a network of national researchers delving into the mind-altering substances.​

In August, Wallach paired with Compass Pathways, the mental health company backed by entrepreneur Peter Thiel, a founder of Paypal and Palantir Technologies.

Compass gave the researcher $500,000 to launch a Drug Discovery Center in West Philadelphia to investigate "new serotonergic compounds." These substances work on a specific neuroreceptor in the brain, 5-HT2A,and include the active ingredients in psilocybin, DMT, mescaline, ibogaine and LSD.

Last week, Compass (NASDAQ: CMPS) announced it is building on its Wallach-led project to include researchers at the University of California, San Diego (UCSD) and the Medical College of Wisconsin (MCW).

"We're looking for new molecules with useful properties," said Wallach, 34, an assistant professor of pharmaceutical sciences. "We're expanding and hope to do exciting work. It would be great to put USciences on the map for determining the direction of the pharmaceutical industry."

Last summer USciences announced three new online certificate programs on marijuana that train students looking to join the rapidly growing industry.

Also last week, USciences announced it was considering a merger with St. Joseph's University to foster growth. The two institutions could become the latest case of consolidation in a sector that is contending with fewer students and high tuition.

Psychedelics—once identified with the counterculture of the 1960s and CIA mind control experiments—are undergoing a renaissance.

About two dozen companies and several nonprofits are leading active investigations. Compass Pathways is running a Phase 2b clinical trial with COMP360, a synthetic version of psilocybin for treatment-resistant depression. Results are due at the end of the year. Psilocybin has been granted a "breakthrough therapy" designation from the FDA, indicating that the agency believes the substance may offer a significant improvement over existing treatments.

"There's a leading hypothesis that these drugs cause changes in synaptic plasticity and strengthen the networks of the brain," Wallach said. "In truth, though that happens, whether that underlies the clinical effects is still not established."

Compass went public last year with a market cap now around $1.6 billion. About a dozen companies pursuing investigations of psychedelics are listed on Canadian stock exchanges.

"There's so much hype," said Wallach, who studied cell biology at Indiana University of Pennsylvania before earning his PhD in Pharmacology and Toxicology at USciences.

His early research focused on cannabinoids, the psychoactive compounds in marijuana. "I think many of them have promise. But the lines are much clearer here with our project."

For now Wallach is investigating non-psilocybin substances that work on the 5-HT2A receptor that exists throughout the human central nervous system.

"Those receptors bind to drugs such as psilocybin and LSD and trigger psychedelic experiences. Those receptors also play a crucial role in higher level functioning of the brain," Wallach said.

"So ketamine and PCP-like substances, those are what we're exploring. We are very focused on the similarities to psilocybin. "

The $500,000 in funds from Compass will let Wallach add staff to his Philadelphia-based team "to use the tools of drug discovery to tailor the molecules for specific therapeutic indications," he said.

When Wallach started as an instructor at USciences in 2017, research was not on his job description, "but the university was kind enough to give me some lab space."

"At that time it was me, Hamilton (Morris, host of Vice TV's docuseries "Hamilton's Pharmacopeia") and several hard working undergraduate students. The responsibilities quickly changed," he said. "I currently have two lab technicians, a PhD candidate student, as well as two undergraduate students and one volunteer, Hamilton. We are also looking to hire a lab technician and post-doctoral researcher immediately. We have collaborators all over the world and so are working with many well-renowned teams."

Wallach, who often appears on Hamilton's Pharmacopeia, keeps his staff busy. He has around 10 projects ongoing at various stages that will lead to publication in scientific journals.

A handful of major universities and research centers are pursuing similar research. Last summer, the University of North Carolina received nearly $27 million from

DARPA, the research arm of the Department of Defense, to develop new psychiatric medicines from psychedelics. In September, Johns Hopkins University in Baltimore launched the first-of-its-kind Center for Psychedelic and Consciousness Research to investigate the substances. The same month, UC Berkeley opened the Center for the Science of Psychedelics. Hopkins, along with New York University, recently completed Phase 3 clinical trials with the nonprofit Multidisciplinary Association for Psychedelic Studies for MDMA-assisted therapy for PTSD.

Lars Christian Wilde, co-founder of Compass Pathways, said he chose Wallach to lead research after a worldwide search.

"Wallach is one of the most knowledgeable people in the psychedelic research world," said Wilde from his home in Dusseldorf, Germany. "But Wallach also has a broad understanding of neuroscience. He had read every paper under the sun. So I asked him if he'd be interested in collaborating. We were fortunate that he said 'yes'."

USciences has a "rich history" with Big Pharma, Wallach said. The school, founded in 1821 as the Philadelphia College of Pharmacy, counts many industry titans among its alumni. Eli Lilly (1907), whose doctoral thesis was on "The Comparative Physiological Effects of Several Varieties of Cannabis Sativa," founded Eli Lilly and Company; Gerard Rorer (1931) started Rorer Pharmaceuticals, now Sanofi; William Warner (1856) founded Warner-Lambert, now part of Pfizer; And Robert L. McNeil began McNeil Laboratories which became part of Janssen.

"I don't think every company is jumping at the bit to enter the psychedelic space, but they're taking notice," Wallach said.

Janssen, a division of Johnson & Johnson (NYSE JNJ) is the only Big Pharma company known to currently market a drug with psychedelic roots. Its FDA-approved esketamine drug, a powerful version of ketamine sold under the brand name Spravato, is used for people with severe treatment-resistant depression.

"Janssen laid the foundation," said Wallach.

Wallach has remained busy during the pandemic. He is working with Bexson Biomedical to develop a subcutaneous pump for ketamine to manage pain. Additionally,

Wallach serves on the advisory board of MindCure Health Inc., a Vancouver, Canada-based psychedelic therapeutics company. In addition to his assistant professor position at USciences, he serves as an adjunct instructor at Cooper Medical School of Rowan University in Camden.

Wallach's virtual partners in the Drug Discovery Center include Adam Halberstadt of UCSD, an expert on the behavioral neuropharmacology of psychedelics and John

McCorvy at Milwaukee's MCW, a pharmacologist who has investigated psychedelic, anti-psychotic, and antidepressant drugs.

"His West Philadelphia lab has already produced 100 novel compounds," Wallach said.

"I see medicinal chemistry in many ways as an art," he said. "Often there is logic to a proposed modification but sometimes the molecule just looks beautiful or you have a gut feeling. The process is exciting, as a minor change in the structure can lead to profound changes in the activity. And you can learn a lot from studying these changes in activity."

"It's fun to create things which may not exist anywhere else in the universe."

Envisioning a psychedelic future for psychiatric treatment

Jason Wallach has a vision. He sees Philadelphia becoming a center for psychedelic studies. From his laboratory at the University of the Sciences, Wallach is leading a network of national researchers delving into the mind-altering substances.

medicalxpress.com

 

[mr peabody]

Are psychedelics the ultimate brain-repair drugs?

by Jeff Nielson | PSW | 6 Aug 2021

Conventional medicine struggles to treat numerous medical disorders for which neurological impairment or dysfunction is a major factor. Psychedelic drugs fix broken brains.

A Revolution is underway.

It started with the Mental Health Crisis.

The Renaissance in psychedelic drug R&D in the 21st century was originally motivated by the quest to tackle stress-related mental health disorders like depression, anxiety, addiction and PTSD.

As the Mental Health Crisis has spiraled into a global pandemic much larger than the COVID-19 pandemic, this original research continues to advance and broaden.

Scientists have discovered that psychedelic drugs have unique medicinal effects. Most commonly, this is described as the capacity of these drugs to “rewire” the human brain.

More specifically, psychedelic drugs appear to be able to “repair broken neural networks” or simply “rebuild broken brains”.

A new form of mental health treatment gains momentum

Armed with this amazing potential, scientists are wasting no time in exploring new avenues with psychedelic drug research.

As noted, this began with stress-related mental health disorders. Here conventional medicine generally offers only mediocre treatment options.

“Rewiring” the brain (with psychedelic drugs) helps sufferers of depression and anxiety to not only address the root causes of their disorder but also helps their brain to process stimuli differently, in a manner that no longer induces stress-related symptoms.

Patients suffering from PTSD are finding that psychedelics-based therapy can help them to both better process and better cope with the traumatic event(s) that seriously affects their mental (and physical) health.

Human clinical trials using psychedelic drugs to treat depression, anxiety and PTSD are already at advanced stages. Compass Pathways (US:CMPS), MindMed Inc (US:MNMD / CAN:MMED), Cybin Inc (CAN:CYBN / US:CLXPF) and Mydecine Innovations Group (CAN:MYCO / US:MYCOF) are among the public companies conducting such research.

Likewise, the key in treating addiction is to (somehow) control or eliminate the addictive cravings that drive substance abuse. Psychedelic drugs appear to neutralize these addictive cravings.​

• Using psilocybin to treat nicotine addiction, 80% of smokers were fully abstinent 6 months later (2014 study)​
• Using ibogaine to treat opioid addiction, 50% of addicts had stopped consuming opioids after one month (2017 study)​

With these early research successes, scientists started asking a very simple question. What other medical patients could benefit from having their brains rewired?

Brain-related R&D in psychedelics mushrooms

Cognitive decline is an obvious candidate for psychedelic drug R&D. Neural pathways in the brain become impaired through physiological decline. Researchers hope that psychedelics-based therapy can rebuild these neural pathways with the goal of at least partially restoring normal functionality.

Private company, Eleusis Ltd is preparing to commence a Phase II clinical trial using micro-doses of LSD to treat Alzheimer’s disease. Alzheimer’s therapy is a multi-billion-dollar treatment market.

Traumatic brain injury (TBI) is another obvious candidate for psychedelics-based R&D. Concussion, the most common form of TBI, is becoming a huge medical treatment issue – both because of the frequency of these injuries and lack of treatment success with conventional medical therapies.

Again, the issue is neurological impairment, this time as the direct result of physical injury. Post-concussion syndrome arises when neurological symptoms don’t recede even after the physical trauma has healed.

Psychedelic drugs are seen as the best hope in rewiring the brain to eliminate neurological symptoms and restore normal functionality.

For scientists like Dr. Dan Engle, a noted international expert in neurology and lead researcher of psychedelics-based therapy for TBI at Mind Cure Health (CAN:MCUR / US:MCURF), the capacity of psychedelic drugs to address these injuries is still regarded as theoretical.

However, for former NHL hockey player Daniel Carcillo (and others), the capacity of psychedelic drugs to treat TBI is already a fact.

Carcillo’s five-year personal journey to find relief from post-concussion syndrome ended with psilocybin, the active ingredient in magic mushrooms. With a clean brain scan today, Carcillo is now CEO for Wesana Health (CAN: WESA / US:DBDID) – another public company pursuing psychedelics-related treatment for TBI.

TBI treatment is already a ~$120 billion per year treatment market. Data Bridge Research forecasts that this will be a $182 billion treatment market by 2027.

Another promising area for psychedelics-related research is autoimmune disorders, especially those with strong neurological components such as multiple sclerosis and Parkinson’s disease. Preclinical psychedelics-based research is already targeting these treatment markets.

A ‘stroke’ of psychedelics genius?

What other medical conditions could benefit from substances that rebuild broken brains? How about stroke?

Stroke is the leading cause of adult disability and the third-leading cause of death. Conventional medicine has some success in addressing the myriad and often severe neurological symptoms that accompany a stroke. But for many survivors, their disability is a life sentence.

Vancouver-based Algernon Pharmaceuticals (CAN:AGN / US:AGNPF) is seeking to change that.

Algernon is targeting DMT-based research as a treatment for stroke, to “promote neurogenesis and neural plasticity, leading to new synaptic connections, and potentially allowing stroke victims to recover faster and with less damage.” Rebuilding the brain.

Algernon has already been in communication with the FDA regarding the initiation of a Phase I clinical trial. The company has filed provisional patent applications in support of this research.

Overall, this is a $30 billion treatment market, projected to reach $65.6 billion by 2030. More multi-billion-dollar potential for psychedelic drug research.

The ultimate brain-repair drugs

Psychedelic drugs will never be able to cure the common cold (or COVID-19). Nor can they repair broken bones or heal wounds.
However, for any medical condition related to neurological impairment or dysfunction, psychedelic drugs are now looking like the Miracle Drugs of the 21st century.

Depression, anxiety, addiction, PTSD, cognitive decline, TBI, autoimmune disorders, stroke. The list of major medical disorders (and treatment markets) now being targeted by psychedelic drug R&D seems to grow nearly by the day.

The potential here is getting increasing numbers of leading medical researchers excited. It’s getting a lot of high-profile investors excited. And it’s now getting the mainstream media excited.

What comes after that? The politicians start to figure things out.

Reform of antiquated drug laws is already underway in the United States, Canada and several other jurisdictions. With the Mental Health Crisis alone now affecting roughly 1 in 4 people globally, there is an imperative need for action in this realm alone.

For rapidly growing numbers of medical practitioners and patients, psychedelic drugs are a revolutionary approach to treating an increasing assortment of disorders – with growing clinical data to support this conviction.

For investors looking to capitalize on this healthcare revolution, most public companies in this space are still priced at ground-floor levels.

A revolution in healthcare doesn’t come around every day. Invest in the opportunity. Support the revolution.

Are Psychedelics The Ultimate Brain-Repair Drugs? | Psychedelic Stock Watch

Psychedelic drugs increasingly appear to be powerful medicinal tools to rebuild broken brains....

psychedelicstockwatch.com

 

[mr peabody]

Imperial College London
​

The Future of Psychedelic Science

Imperial College London | Neuroscience News | 25 Jul 2021

From treating depression and other mental health disorders, to helping relieve chronic pain, researchers discuss the advantages and implications of psychedelic treatments.

In 2019 a small group of researchers at Imperial established the world’s first dedicated centre for research into the action and clinical use of psychedelic compounds.

Two years on, the Centre for Psychedelic Research has completed landmark studies into the therapeutic potential of magic mushroom compound psilocybin for depression, exploring the ‘waking dream state’ linked to ayahuasca, and digging deeper into the science of micro-dosing with LSD.

Ryan O’Hare spoke to Dr Robin Carhart-Harris, the head of the Centre, to discuss what’s in store for the future.

Here are five of the big questions the work of the Centre for Psychedelic Research hopes to answer in the future.​

How do psychedelics change our brain? ​

Work from the Centre has shown that psilocybin may help to ‘reset’ the brain and break out of long-entrenched patterns of activity seen in depression.

Early, unpublished follow up work from the team shows that when people are shown emotionally charged faces, SSRI antidepressants (drugs like fluoxetine and escitalopram) blunt the response to all faces, but psilocybin may only dampen the negatively charged faces.

Dr Carhart-Harris explains: “With the Prozac-like antidepressant…we see a dampening or muffling of the brain’s responsiveness to emotional stimuli relative to the psilocybin. That makes sense because the psilocybin is more like an emotional recalibration or reset, whereas the SSRI [antidepressant] is more like taking the edge off emotional intensity which helps with stress management.”

Delving into this further, the Centre plans to study how psychedelics change the activity of our brains. Studies are due to begin analysing brain waves and MRI data in volunteers given psilocybin and DMT (the active compound found in the psychedelic Amazonian brew ayahuasca) to compare their brain activity before and after their experience.​

How are people using psychedelics and can we reduce potential harms? ​

Over the last two years, the team has been gathering real-world data on how people are using psychedelic drugs, gaining valuable insights.

Through the ongoing Psychedelic Survey and the imminent launch of the MyDelica app, the team hopes to use a data-driven approach to help inform people intent on taking psychedelics of the importance of the setting, wider context and psychological state on outcomes.

One of the aims is to educate people and provide advice, which may help to reduce harms and ultimately improve psychological outcomes.

“We’ve actually seen, looking at some recent data, that use of psychedelics over the last 10 years has increased exponentially,” explains Dr Carhart-Harris.

“With the online sampling and the app we’re developing, the intention is to de-risk some of that and provide harm reduction, psycho-education advice to try and keep people safe, essentially.”

The researchers warn that people should not attempt to self-medicate or replicate findings from clinical trials with psychedelics, as the team provided a special therapeutic context for the drug experience and things may go awry if the extensive psychological component of the treatment is neglected.​

Could psilocybin help to treat anorexia? ​

Following positive initial results in a small trial of psilocybin assisted therapy for depression, the Centre is set to look at whether the same approach could help with anorexia nervosa.

Building on evidence from a small number of historical case studies of using psychedelics in eating disorders, the team will trial psilocybin-assisted therapy in young adults with anorexia to see if the treatment is feasible and effective.

According to the Centre: “Anorexia nervosa is the most fatal of all psychiatric conditions. With the current paucity of effective pharmacological and psychological treatments, and fewer than half of those diagnosed making a full recovery, there is a great need for new treatment avenues to be explored.”

A small study is due to begin in the coming months.​

Can psychedelics offer relief from chronic pain? ​

Despite numerous advances in pain relief, effective and non-addictive treatments for long-term chronic pain – such as lower back pain – remain elusive.

There is mounting evidence that in those with chronic pain conditions, the brain connections which relay and processes pain signals can become reinforced and strengthened over time, as part of a feedback loop which sensitises them even more to feeling pain and associated negative emotional response.

Psychedelics could offer an opportunity to ‘reset’ these neural pathways. The hope is that by disrupting this entrenched pain circuitry, psychedelics might offer a way to reduce the brain’s over-sensitivity to pain signals.

According to Dr Carhart-Harris, the Centre hopes to begin a study later this year.​

What is consciousness? ​

One of the more fundamental areas researchers are hoping to advance with psychedelics is our understanding of human consciousness.

By analysing brain activity before, during and after psychedelic experiences, the team hopes they can shine more light on brain states linked with the so called ‘mystical experience’ associated with psychedelics.

The team has already laid some of the groundwork, with its previous DMT research into the ‘waking dream state’ linked to ayahuasca. It is thought that a better understanding of how different patterns of brain activity give rise to hallucinations and waking consciousness could enable us to nudge the brain when it’s stuck in certain negative patterns.

Psychedelics could potentially ‘reset’ brain activity and enable people to break out of entrenched, negative behaviour patterns – linked to addiction, depression or pain, for example – which have been reinforced and strengthened over a person’s lifetime.

“DMT is a particularly intriguing psychedelic,” Dr Carhart-Harris commented previously. “The visual vividness and depth of immersion produced by high-doses of the substance seems to be on a scale above what is reported with more widely studied psychedelics such as psilocybin or ‘magic mushrooms’,” he explained.

“Our sense it that research with DMT may yield important insights into the relationship between brain activity and consciousness, and our previous work is a first step along that road.”

The Future of Psychedelic Science - Neuroscience News

From treating depression and other mental health disorders, to helping relieve chronic pain, researchers discuss the advantages and implications of psychedelic treatments.

neurosciencenews.com

 

[mr peabody]

The extraordinary therapeutic potential of psychedelic drugs, explained

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

by Sean Illing | VOX | 8 Mar 2019

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.

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.

The image on the left is of a human brain on a placebo, and the image on the right is of a brain on psilocybin.

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.

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 above ground 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 mainstream 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.

https://www.vox.com/science-and-hea...-mushrooms-ayahuasca-depression-mental-health​

 

[mr peabody]

Why psychedelics could be the new class of antidepressants

by Jack Dutton | The Independent

In a lab in Basel in April 1943, Swiss scientist Albert Hofmann accidentally touched his hand with his mouth while he was synthesising a chemical intended to stimulate respiration and the nervous system. After ingesting the drug, he realised he had made something far more potent: what we now know as LSD. In the 1950s and 1960s, thousands of LSD studies were carried out after a group of pioneering psychiatrists showed that hallucinogenic drugs had therapeutic potential. It became the age of psychedelics.

In the 50 years since this golden era, scientific progress in psychedelic research has been limited. A backlash against the hippy counterculture – “the war on drugs” – halted research into psychedelics. In 1971, the UK parliament introduced the Misuse of Drugs Act, classifying psilocybin, LSD and DMT as illegal class A drugs.

However, this year could see a watershed moment in British drug policy. After the government rejected the use of medicinal cannabis for a six-year-old epileptic boy who had 3,000 seizures a year, the home secretary Sajid Javid ordered a review of the drug being used for therapeutic purposes.

Only weeks after the cannabis review was announced last month, the London-based Psychedelic Society, a campaign group that believes that psychedelics can improve wellbeing, launched its Psychedelics for Mental Health campaign. The launch discussed the rescheduling of psilocybin, the psychedelic compound found in magic mushrooms, from schedule 1 to schedule 2.

The government sees schedule 1 drugs – including LSD, MDMA and cannabis – as having no therapeutic value, meaning it is illegal to possess or prescribe them. Schedule 2 drugs – such as methadone and diamorphine (heroin) – can be prescribed and legally possessed by pharmacists and doctors. Rescheduling a drug from schedule 1 to schedule 2 makes it much cheaper to conduct research into its effects.

“It feels like the narrative around these substances is changing very quickly,” says Stephen Reid, the founder of the Psychedelic Society. “We anticipated that now would be a good time to make a serious push for rescheduling. What we didn’t know when we started planning the campaign was that there would be this news around cannabis. It is a further sign of how fast things are changing.”

Depression is a growing problem and antidepressants continue not to work for up to half of the people who take them, according to research published in the journal Brain, Behaviour and Immunity. Reid and other representatives of the society believe that psychedelics could potentially treat depression.

Psilocybin and depression

There have been several studies that support the society’s theory. One study, led by Dr Robin Carhart-Harris, head of psychedelic research at Imperial College London tested 20 participants who were suffering from severe depression. Dr Rosalind Watts, clinical psychologist at Imperial College London, who was also involved in the study, says that participants went through psilocybin and therapy sessions with a “guide”, a therapist who would interact with them when they were taking the drug. A psychiatrist also interviewed the participants.

After three months, the antidepressant effects were found to be greater for those taking psilocybin than for people taking typical antidepressants and therapy. Patients said they went from feeling “totally disconnected” with themselves and the world to “connected”, and from repressing and avoiding emotions and memories to accepting them.

Watts is about to start work on her next study, which compares the effects of psilocybin with a leading antidepressant, escitalopram. Unlike antidepressants, which are taken daily, psilocybin therapy would take place several times over a series of months, with top-up sessions every few months until the patient decides that they no longer need it.

If psilocybin therapy hits the mainstream, psychiatrists would need training for the new type of therapy, which would cost time and money. It also helps if the “guide” has had their own psychedelic experiences, so they can better understand the patient’s.

Building a coalition

Although challenges lie ahead, the Psychedelics for Mental Health Campaign is gaining momentum. Caroline Lucas MP, the former leader of the Green Party, has recently backed the campaign.

The movement has also seen support from popular musicians, including Jon Hopkins, who told The Guardian in April that psilocybin inspired his latest album, Singularity. Among others, the project has also received backing from founder of DrugScience and the government’s former chief drugs adviser, Professor David Nutt; The Beckley Foundation; and publication Live Learn Evolve.

“At this stage, it’s about building a coalition,” says Reid. “There’s never been a serious coalition before of organisations and high profile individuals calling for change in this area. This is now backed by a number of leading drug policy institutions in the UK.”

The Psychedelic Society is waiting until the review of medical cannabis is complete, though it’s not entirely clear about how long that will take. Reid anticipates it taking a few months before he looks to begin bringing a case to the Home Office.

“If there is a decision to change the schedule of cannabis, I think that will set an excellent precedent for other substances being rescheduled,” he says. “The first intention off the back of the cannabis review is to push further on psilocybin.”

The Psychedelic Society is planning on doing some extensive polling of the current state of attitudes on drugs policy in the UK. From there, it will work out the best calls to make for manifestos in the next general election.

Although there is still plenty of ground to make up since the Seventies, Reid is optimistic.

“I hope there will be much, much stronger suggestions than simply rescheduling by the time 2022 comes around,” says Reid. “Jeremy Corbyn, for example, has already backed the decriminalisation of small amounts of medical cannabis and the government seems to be rescheduling it. Things are moving very, very quickly."

https://www.independent.co.uk/news/...tidepressant-albert-hofmann-lsd-a8437201.html​

 

[mr peabody]

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The potential of psilocybin therapy to transform mental healthcare*

by Guy Goodwin | Technology Networks | 28 Oct 2021

It is estimated that 5% of adults currently suffer with depression globally, often in combination with anxiety. According to a UK publication, it is thought that as many as 10% of the population will experience depression within their lifetime.1

The consequences of mental disorders are far-reaching. Those suffering with conditions such as depression may perform poorly in lots of other areas of life. It is considered a leading cause of disability worldwide and in its most severe form is estimated to reduce life expectancy by 10-20 years compared to the general population.2

The prevalence of these disorders is increasing to crisis levels. There has been a 13% rise in mental health conditions in the last decade.3,4 COVID-19 has exacerbated this trend, particularly in young people. The effects of the pandemic have not yet been fully understood but the isolation produced by lockdown has been shown to have a negative effect on many people’s mental health. It has created new barriers for people already suffering with mental illness.

Depression promotes social withdrawal and a large proportion of people with mental disorders either receive no treatment at all or experience long delays. For those who do receive treatment, current methods are too often inadequate.5

There are two commonly used treatment pathways available to patients with depression. The first is psychological, where therapists guide patients through techniques such as cognitive behavioral therapy (CBT) to address their negative thought patterns. The second is medical, usually by prescribing selective serotonin reuptake inhibitors, or SSRIs. However, the effects of either approach are variable and only help around half of patients who receive treatment.

Where the effects of two or more trials of antidepressants are negligible, patients are said to have treatment-resistant depression. Very commonly, such patients remain in limbo between primary care, where the resources and options are limited, and secondary care, where patients are only admitted in extreme cases.

Despite the evident and growing need for effective mental health treatment there has been a critical lack of innovation in the field. New treatment options are needed to change the present impasse and tackle the growing mental health crisis. Important first steps towards this have been made, with the approval of esketamine as a therapy for treatment-resistant depression. The drug, a derivative of ketamine, is administered as a nasal spray in conjunction with oral antidepressants. More sophisticated brain stimulation therapies are also emerging that stimulate the brain by targeting specific areas with magnetic or electrical waves to help treat depression.

Recent advances in psilocybin therapy have the potential to turn the page in the mental health crisis. Modern experimental techniques have revealed the mechanisms behind psychedelic compounds and the opportunity to harness that mechanism for medicinal use. Psilocybin, derived from magic mushrooms, was first isolated and identified in 1958 by Albert Hofmann. After a flurry of research in the following decade, medical supplies of the substance dropped as recreational use of the drug was banned. Following a hiatus of 50 years, scientific research has produced psilocybin in a pure and stable form as COMP360 and with a renewed therapy wrapper. We have now started to build evidence of its efficacy and effectiveness.

The process of psilocybin therapy, still under investigation, has three stages. First, patients get to know about the therapy and their therapist in a preparatory session so they can form an informed and trusting relationship. The patient receives their dose of psilocybin in the next session. They are placed in a supportive environment, listening to music and wearing an eye mask to help them focus internally. Two therapists are present throughout the session, which typically lasts 6-8 hours. In the final stage, patients are encouraged to discuss their experience with the therapist.

The promise of psilocybin therapy is unique. It is a hybrid strategy, combining the two treatment pathways currently available to those living with depression, incorporating psychological change and pharmaceutical intervention . Psilocybin is thought to stimulate neuroplasticity in the brain, encouraging new ways of thinking and shifting patient perspective. With the guidance of their therapists in the final session, it is thought that patients can use their experience to help them break fixed habits of unhelpful thinking and behavioral patterns.

Small-scale studies have given early indications of the potential effectiveness of psilocybin therapy but larger, multi-center trials are required to generate the evidence required for medical approval. The release of the COMPASS Pathways phase IIb trial results could mark a significant step on the road to providing safe access to these therapies.

The phase IIb trial is dose finding and investigates the effectiveness of the proprietary, synthesized formulation of psilocybin, COMP360, in patients with treatment-resistant depression. It involved 233 patients living with the disorder – the largest sample size for any trial investigating psilocybin or similar therapy. The study aims to provide the first instance of statistically powerful, scientifically rigorous evidence of psilocybin therapy’s effectiveness in treating a mental health condition.

COVID-19 has made the progression of studies like this one all the more important. It is a remarkable achievement that the study has progressed during and despite the pandemic and demonstrates the commitment of all staff and clinicians involved in the trial. Patients too have made sacrifices, disrupting their existing treatments to participate in the trial. The ease of patients withdrawing from the antidepressants they were previously on speaks to the acceptability of psilocybin therapy in the community and the sense of excitement at the idea of a potential new mental health care therapy.

The results will pave the way for larger phase III trials expected to begin in 2022. This is the next step on the journey in providing access to this therapy for those living with this debilitating condition. However, psilocybin therapy is not simply “antidepressant”. The treatment has more general effects that could, in time, be applied to other disorders. Any illness that involves repetitive, stuck thinking or behavior could benefit from psilocybin therapy; these will include eating disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). The prospect of harnessing this powerful neurobiology has significant potential in treating many of the most serious mental disorders. If approved, psilocybin therapy may provide the tipping point to a new way of thinking about mental health care, stimulating innovation across conditions and benefitting a huge number of patients. This is only the beginning.

*From the article (including references) here :

Thinking Differently: The Potential of Psilocybin Therapy To Transform the Mental Healthcare Landscape

Poor mental health is a growing burden on global healthcare systems. In this opinion piece, Compass Pathways chief medical officer Professor Guy Goodwin reviews currently available treatments options and the results from his company's new clinical trial into the efficacy of the psychedelic...

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