DEPRESSION | +80 articles

[mr peabody]

Psychedelics as Antidepressants

by Austin Lim | Scientific American | 30 Jan 2021

The treatments of the future may arise from a long-stigmatized class of drugs

The first modern antidepressants were originally tuberculosis medications, created from leftover World War II rocket fuel. In 2019, the Federal Drug Administration approved Spravato for depression, a chemical that was originally a veterinary anesthetic and later used recreationally as a club drug.

Why shouldn’t tomorrow’s antidepressants also come from unexpected sources?

Rising COVID infection rates and death tolls lead millions to worry about their own health and safety as well as that of loved ones. These concerns compound daily stressors that can include grief, economic insecurity, job loss, food and housing insecurities—all factors that are contributing to rising suicide rates.

The reliable joyful distractions such as weddings, family gatherings and spontaneous get-togethers are on hold. Unsurprisingly, anxieties combined with decreased human interaction have led otherwise healthy people to depression and a sudden increase in prescriptions of antidepressant medications.

And for some people, these drugs are effective at keeping a person out of their persistent cycle of negative thoughts, a symptom that defines clinical depression. As of 2018, nearly one in eight Americans use antidepressants. Unfortunately, more than a third of patients are resistant to the mood-improving benefits of medicine’s best antidepressant drugs.

These people are not completely out of options, and science is steadily working to find ways to help them. There are chemicals already out there that can restore their mood balance, and in some cases, even save their lives. Unfortunately, these drugs have a name that wrongfully conjures up controversy and alarmist news headlines: hallucinogens.

Chemicals such as LSD, psilocybin and DMT are more accurately called “serotonergic psychedelics” among the neuroscience community. Outside of this group however, many people don’t think of these compounds as antidepressants to be distributed by white-coat-wearing psychiatrists. Instead, they imagine whimsical blotter papers passed around by washed-up hippies at Grateful Dead concerts.

And yet, researchers in the U.K. have already been given the green light to begin clinical trials for using DMT for treating depression.

To a neuroscientist whose focus is the striatum, a brain area involved in complex conditions ranging from depression to addiction, it’s evident that these drugs have tremendous promise for a safe, happier future.

Many states are looking to reevaluate the legal status of psychedelics. This is a start at improving the public perception of psychedelic use, which can ultimately encourage more to seek psychedelic therapy in psychiatric practice.

Denver, Oakland and Santa Cruz, Calif., are among the first American cities to legalize psilocybin. The recently approved Measure 110 in Oregon decriminalizes LSD. Legislation has been moving forward in New Jersey, Washington, D.C., and Vermont to downgrade the severity of punishments for possession of psychedelics.

All of these measures represent a reframing that looks at the science of the drug rather than a set of beliefs about the drug.

The stigma against psychedelics could be a result of its status as a controlled substance. Since its criminalization in the 1960s and subsequent vilification by the media, LSD was seen as a public nuisance and enemy. But prior to this, the National Institutes of Health funded more than 130 studies to explore the benefits of psychedelic therapy.

Today, psychedelics still fall into the federal classification of Schedule I drugs, which carry the highest penalties associated with their possession and use. Because of government regulations, controlled substances are difficult to study, even in a clinical setting.

But this hasn’t completely stopped researchers from examining their benefits. Recent studies have arrived at several noteworthy conclusions.

First and foremost is the safety of these drugs. At the correct doses, psychedelics are well tolerated, producing only minor side effects such as transient fear, perception of illusions, nausea/vomiting or headaches. These fleeting side effects pale in comparison to the severity of commonly prescribed antidepressants, which include dangerous changes in heart rate and blood pressure, paradoxical increases in suicidality, and withdrawal symptoms.

As far as outcomes go, psychedelics in combination with psychotherapy are remarkably efficient at treating depression. Compared to selective serotonin reuptake inhibitors, or SSRIs, the current gold standard in antidepressant medication, psychedelics have a faster effect on patients, sometimes effective with only a single therapy session. On the other hand, anti-depressants often take weeks before a reversal of depression is observed.

Psychedelics also have a longer-lasting effect than an SSRI regimen. A 2015 study of more than 190,000 Americans demonstrated that past history of psychedelic use decreases the odds of suicidal thoughts or actions over the course of a lifetime, whereas a history of other drug use (such as sedatives or inhalants) increases these risks.

Psychedelic therapy may reverse the symptoms of other complex psychiatric conditions. Evidence suggests that anxiety, obsessive-compulsive disorder and tobacco or alcohol misuse disorder may also be treated with psychedelics.

It is still unclear how much these treatments will cost, but one study predicts that psychedelic therapy for post-traumatic stress disorder could save each patient $100,000 over a 30-year window.

Putting aside preconceptions about these drugs, if objectively comparing their properties to the other drugs that someone can easily buy at a convenience store, their safety becomes apparent.

Psychedelics have extremely low addictive potential. Tobacco is regarded as one of the most addictive substances, ranked just behind heroin and cocaine—not to mention the significant shortages in life span that make tobacco use the number one leading cause of preventable death.

Alcohol use contributes significantly to risk of harm to oneself and others. However, using alcohol and using tobacco products are both widely perceived as socially acceptable. “Why aren’t you drinking?” is a common (yet intrusive and unfair) question in social circles.

They are also very safe compounds with low toxicity profiles. A woman who took a dose of LSD 550 times higher than a typical dose lived without any medical attention; imagine the life-threatening consequences of drinking just five times as much alcohol as normal. (Not only did she survive, but she also noticed a significant reduction in her chronic pain condition, and was able to decrease her usage of morphine as part of her pain management treatment.)

Certainly, people have been injured while taking psychedelics. Most famously, Diane Linkletter, daughter of radio and TV personality Art Linkletter, tragically died by suicide in 1969, presumably while taking LSD. Following her death, Linkletter became a prominent voice in the anti-LSD movement. It is unclear whether LSD led her to suicide, but no drugs were detected in her autopsy report.

Other documented cases include instances of people using psychedelics of questionable purity or in unknown doses, and almost always in conjunction with other drugs.

Psychedelics given in a therapeutic context are pure substances, created by trained chemists and pharmacologists. Dosages are therefore carefully calculated to produce the minimum necessary therapeutic effect.

Equally importantly, these drugs are delivered under close supervision by behavioral psychiatrists who carefully monitor the mindset and the surroundings of the patient. This limits the outside influences that could cause the patient to behave unpredictably, hurting themselves or others.

Psychedelics as Antidepressants

The treatments of the future may arise from a long-stigmatized class of drugs

www.scientificamerican.com

 

[mr peabody]

Psilocybin treatment found to relieve major depression, study*

Johns Hopkins Medicine | 4 Nov 2020

In a small study of adults with major depression, Johns Hopkins researchers report that two doses of psilocybin, given with supportive psychotherapy, produced rapid and large reductions in depressive symptoms, with most participants showing improvement and half of study participants achieving remission through the four-week follow-up.

A compound found in so-called magic mushrooms, psilocybin produces visual and auditory hallucinations and profound changes in consciousness over a few hours after ingestion. In 2016, Johns Hopkins Medicine researchers first reported that treatment with psilocybin under psychologically supported conditions significantly relieved existential anxiety and depression in people with a life-threatening cancer diagnosis.

Now, the findings from the new study, published Nov. 4 in JAMA Psychiatry, suggest that psilocybin may be effective in the much wider population of patients who suffer from major depression than previously appreciated.

“The magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market,” says Alan Davis, Ph.D., adjunct assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Because most other depression treatments take weeks or months to work and may have undesirable effects, this could be a game changer if these findings hold up in future ‘gold-standard’ placebo-controlled clinical trials.” The published findings cover only a four-week follow-up in 24 participants, all of whom underwent two five-hour psilocybin sessions under the direction of the researchers.

“Because there are several types of major depressive disorders that may result in variation in how people respond to treatment, I was surprised that most of our study participants found the psilocybin treatment to be effective,” says Roland Griffiths, Ph.D., the Oliver Lee McCabe III Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Center for Psychedelic and Consciousness Research. He says the major depression treated in the new study may have been different than the “reactive” form of depression in patients they studied in the 2016 cancer trial. Griffiths says his team was encouraged by public health officials to explore psilocybin’s effects in the broader population of those with major depressive disorder because of the much larger potential public health impact.

For the new study, the researchers recruited 24 people with a long-term documented history of depression, most of whom experienced persisting symptoms for approximately two years before enrolling in the study. The average age of participants was 39; 16 were women; and 22 identified themselves as white, one person identified as Asian and one person identified as African American. Participants had to taper off any antidepressants prior to the study with the help of their personal physician to ensure safe exposure to this experimental treatment.

Thirteen participants received the psilocybin treatment immediately after recruitment and after preparation sessions, and 11 participants received the same preparation and treatment after an eight-week delay.

Treatment consisted of two psilocybin doses given by two clinical monitors who provided guidance and reassurance. The doses were given two weeks apart between August 2017 and April 2019 at the Johns Hopkins Bayview Medical Center Behavioral Biology Research Building. Each treatment session lasted approximately five hours, with the participant lying on a couch wearing eyeshades and headphones that played music, in the presence of the monitors.

All participants were given the GRID-Hamilton Depression Rating Scale – a standard depression assessment tool – upon enrollment, and at one and four weeks following completion of their treatment. On the scale, a score of 24 or more indicates severe depression, 17–23 moderate depression, 8–16 mild depression and 7 or less no depression. At enrollment, participants had an average depression scale rating of 23, but one week and four weeks after treatment, they had an average depression scale score of 8. After treatment, most participants showed a substantial decrease in their symptoms, and almost half were in remission from depression at the follow-up. Participants in the delayed group didn’t show decreases in their symptoms before receiving the psilocybin treatment.

For the entire group of 24 participants, 67% showed a more than 50% reduction in depression symptoms at the one-week follow-up and 71% at the four-week follow-up. Overall, four weeks post-treatment, 54% of participants were considered in remission – meaning they no longer qualified as being depressed.

“I believe this study to be a critically important proof of concept for the medical approval of psilocybin for treatment of depression, a condition I have personally struggled with for decades,” says entrepreneur and philanthropist Tim Ferriss, who supported the funding campaign for this study. “How do we explain the incredible magnitude and durability of effects? Treatment research with moderate to high doses of psychedelics may uncover entirely new paradigms for understanding and improving mood and mind. This is a taste of things to come from Johns Hopkins.”

The researchers say they will follow the participants for a year after the study to see how long the antidepressant effects of the psilocybin treatment last, and will report their findings in a later publication.

Griffiths, whose research with psilocybin, begun in the early 2000s, was initially viewed by some with skepticism and concern, says he is gratified by Johns Hopkins’ support and heartened by the dozens of startups and research labs that have followed suit with their own research. He says numerous companies are now actively working to develop marketable forms of psilocybin and related psychedelic substances.

According to the National Institute of Mental Health, more than 17 million people in the U.S. and 300 million people worldwide have experienced major depression.

*From the article here: https://www.hopkinsmedicine.org/new...locybin-relieves-major-depression-study-shows​

 

[mr peabody]

Psychedelic therapy could 'reset' the depressed brain

by Rachel Schraer | BBC | 15 Mar 2021

A powerful psychedelic drug known for its part in shamanic rituals is being trialled as a potential cure for depression for the first time.

Participants will be given the drug DMT, followed by talking therapy.

It is hoped this could offer an alternative for the significant number of people who don't respond to conventional pills for depression.

Psychedelic-assisted therapy might offer longer-term relief from symptoms, some researchers believe.

A growing body of evidence indicates other psychedelic drugs, particularly alongside talking therapy, are safe and can be effective for treating a range of mental illnesses.

This will be the first time DMT is given to people with moderate to severe depression in a clinical trial.

Dr Carol Routledge, the chief scientific officer of Small Pharma, the company running the trial said: "We believe the impact will be almost immediate, and longer lasting than conventional antidepressants."

Spirit molecule

The drug is known as the "spirit molecule" because of the way it alters the human consciousness and produces hallucinations that have been likened to a near-death experience.

It is also the active ingredient in ayahuasca, a traditional Amazonian plant medicine used to bring spiritual enlightenment.

Researchers believe the drug might help loosen the brain's fixed pathways, which can then be "reset" with talking therapy afterwards.

Dr Routledge likened the drug to "shaking a snow globe" - throwing entrenched negative thought patterns up in the air which the therapy allows to be resettled into a more functional form.

But this hypothesis still needs to be proven.

The team is consulting Imperial College London, which runs the pioneering Centre for Psychedelic Research.

As part of the study, they hope to investigate whether the drug can be administered as a one-off or as part of a course.

Subjects will be followed up for at least six months to see how long the effects of the treatment last.

Ketamine clinic

Meanwhile, a ketamine-assisted therapy clinic is set to open in Bristol next week.

While the drug is already used for depression in clinics like the ketamine treatment service in Oxford, it is not accompanied by psychotherapy.

Rather, it is used to provide temporary relief from symptoms for people who have very serious, treatment-resistant depression.

So-far unpublished researched presented at a conference by professor of psychopharmacology at the University of Exeter, Celia Morgan, suggests ketamine accompanied by therapy has much longer-lasting effects.

Prof Morgan said there was mounting evidence that drugs, including psilocybin, LSD, ketamine and MDMA (Ecstasy), were safe and could play a role in the treatment of mental health disorders.

And there was some early evidence they could have longer-term effects than the medicines conventionally prescribed as antidepressants, known as SSRIs, but more research was needed.

"They also worked using a completely different mechanism," Prof Morgan explained.

Long-lasting change

While conventional drugs may numb negative feelings, "these drugs seem to allow you to approach difficult experiences in your life, sit with that distress and process them," she said.

"It might be getting at something more fundamental that was the root cause of the problem," Prof Morgan said.

"Through that we think you can get much more long-lasting change."

Prof Michael Bloomfield, a consultant psychiatrist at University College London, said although it was a "really exciting" area of research, caution was needed in overpromising the drugs' potential.

"It was also a field of therapy that could be open to abuse and misuse," he said.

Prof Morgan also stressed the importance the drugs being used within the context of therapy as there were concerns that "people might think they can give it a go with some recreational drugs".

"But that's really not how it works" she said.

Psychedelic therapy could 'reset' depressed brain

A powerful hallucinogen used in shamanic rituals is being trialled as a potential depression cure.

www.bbc.com

 

[mr peabody]

Psilocybin may provide relief from depression equivalent to, or better
than, an SSRI antidepressant.

Psilocybin therapy may work as well as common antidepressant

by Zoe Cormier | Scientific American | 25 Apr 2021

For the first time, a randomized controlled trial shows the psychedelic offers potent, if short-term, relief in comparison with an SSRI.

The first randomized controlled trial to compare the illicit psychedelic psilocybin with a conventional selective serotonin reuptake inhibitor (SSRI) antidepressant found that the former improved symptoms of depression just as well on an established metric—and had fewer side effects. The study was fairly small, however, and was not explicitly intended to show how well the drugs stacked up on other measures of well-being.

In a study published on Thursday in the New England Journal of Medicine, psychiatrist David Nutt, psychologist Robin Carhart-Harris and other researchers, all then at Imperial College London, conducted a six-week trial of 59 participants split into two groups. One group was given a full dose of psilocybin (the active ingredient in “magic mushrooms”) in combination with psychotherapy. The other received daily amounts of the SSRI escitalopram plus two minuscule amounts of psilocybin with psychotherapy. All of the participants suffered from major depressive disorder (MDD), which affects roughly 10 percent of the U.S. population in a given year.

Researchers had previously conducted an open-label trial (in which subjects and practitioners know which treatment they are getting) and four randomized controlled trials of psilocybin for depression and anxiety. But until now, no randomized controlled trials had directly compared psilocybin with an SSRI.

“Conventional antidepressants have dominated psychiatry for so long, so it is noteworthy to compare psilocybin—still an illegal drug—with a standard first-line treatment,” says Carhart-Harris, now at the University of California, San Francisco’s Neuroscape center. Psilocybin is designated as a Schedule I substance, defined as having 'no currently accepted medical use and a high potential for abuse.' “This study clearly suggests we need to change the legal status of psilocybin because it is starkly at odds with the data,” Carhart-Harris says.

The researchers used a variety of measures to score study subjects for depressive symptoms and employed the 16-point Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16)—a self-assessment questionnaire—as the study’s primary outcome. The QIDS-SR-16 mean scores did not show a statistically significant difference between the group given psilocybin alone and the one given the SSRI after six weeks.

But the psilocybin group showed significantly larger reductions in suicidality, anhedonia (a lack of the ability to feel pleasure), and standard psychological scores for depression known as the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D). In particular, Carhart-Harris notes, within the 16 items in the QIDS-sR-16 questionnaire, many of the differences were highly significant: 70 percent of subjects in the psilocybin group responded to the treatment, compared with 48 percent of those in the SSRI group. The difference in remission rates was also statistically significant: the rate in the psilocybin group was 57 percent, and it was 28 percent in the escitalopram group.

“Looking at their data, it’s very clear to me that there is a substantial difference between those two groups in precisely the direction we would have predicted,” says Roland Griffiths, director of the Johns Hopkins Center for Psychedelic and Consciousness Research, who published his own “landmark” paper in JAMA Psychiatry last year: the first randomized controlled trial to examine psilocybin therapy for MDD.

“One of the most notable aspects of this new paper from Imperial College London is where it is being published, the NEJM, which is a marker for where mainstream medicine is situated,” says psychiatrist Charles Grob of the University of California, Los Angeles, who was also not involved in this study and has studied psilocybin and other psychedelics for decades. His most cited papers examined the psilocybin’s ability to reduce anxiety and improve quality of life in patients with terminal cancer. “This also indicates where we are as a society,” Grob says. “In 2006, when we began recruiting for our studies on cancer, it was very challenging.” By comparison, the scientists conducting the new trial were overwhelmed with volunteers: they ultimately screened 1,000 people, of whom they selected only 59.

"The team anticipated that this high number of “self-referrals,” most of whom experienced a strong preference for psilocybin over an SSRI, would likely influence the study’s outcomes," Carhart-Harris says. Those who received escitalopram would probably express disappointment, and those receiving the psilocybin could improve even more than they would if the study had been conducted 10 years ago. Many factors make careful statistical scrutiny of psychedelic therapies difficult—and raise the question of whether “blinding” subjects to the treatment they receive is even possible with such strong psychoactive drugs.

The researchers attempted to minimize this effect by telling people in both groups they would receive psilocybin to set up equivalent expectations. They gave both groups the standard experience of a psychedelic dosing: an extended, four-to-six-hour session in which each subject was instructed to lie still while blindfolded and listening to music, with one or two therapists in the room for support. The participants assigned to the psilocybin group were given a 25-milligram dose of psilocybin for the full effect. Those in the escitalopram group were given a one-milligram subperceptual “microdose” with no obvious psychedelic effects. Finally, after the first dosing, the team gave every subject a bottle of pills and instructed them to take one per day: the escitalopram group received the SSRI, whereas those in the psilocybin group simply took a placebo.

“This is an incredibly exciting topic, but it does require very rigorous scientific methodology to really understand the safety and efficacy of these treatments,” says psychiatrist Gerard Sanacora, an associate professor at the Yale School of Medicine and director of the Yale Depression Research Program. "This is a relatively small number of people with no placebo group, so we are limited in what conclusions we can draw from this data,” he says. “I look at this data as promising and warranting this study. But sometimes the excitement does get ahead of the science, so we need to be honest in saying what the limitations are.”

Sanacora also notes that the psychotherapeutic component of the study—which gave equal amounts of preparation, counseling and follow-up to both the escitalopram and psilocybin groups—is unusual and noteworthy. Every participant received between 38 and 40 hours of psychotherapy in total—roughly double the normal amount subjects in most psychedelic studies receive. “That kind of psychosocial intervention is really quite powerful,” he says.

“It’s really important for us to recognize that, in the study, both groups did well, and the reason they both did well is because there was so much care and attention in this study,” says psychologist Rosalind Watts, a co-author of the paper and lead of the clinical portion of the research. She is now a member of the advisory board at Synthesis, a center that offers psychedelic therapy retreats in the Netherlands. That nation is one of the few jurisdictions where psilocybin (in the form of truffles) is legal. In Oregon, citizens voted in November 2020 to legalize psilocybin therapy for medical purposes.

The psychological component of psychedelic therapy tends to be underemphasized by both scientists and the media, yet it is thought to be integral to the therapy’s efficacy, Watts says—in particular because these experiences can be unsettling, powerful, confusing and even scary. The feeling of “safety” and an “alliance” with a therapist is often crucial for any psychological breakthrough. This is especially true for many patients with depression, who often lack confidence to try new treatments after many have failed.

“I thought the drug might work for some people but probably would not work for me. I was quite terrified because I didn’t really trust my brain; I felt like it was always working against me,” says Ali Thorne, a 32-year-old registered nurse in the U.K., who took part in the trial after suffering from depression for two decades. “I think the trial—both the psilocybin and the psychological support—really saved my life.” (Following the study, participants were informed which treatment they had received.)

Yet while some of the subjects experienced enduring benefits after the trial concluded, others relapsed into depression. Leonie Schneider, a 44-year-old Greek woman living in England, was one of the participants who became depressed again, following a particularly challenging period of unfortunate events that included severe financial difficulties as a result of COVID and family members with a terminal illness. “I became more depressed than I’d been in my entire life, and it was even more difficult because I had come off the medication I had previously relied on prior to the trial. Plus, COVID was kicking off, and I didn’t have the stabilizing crutches I normally had to cope,” she says.

Schneider notes, however, that two decades of trying a multitude of SSRI antidepressants in addition to talk therapy did not give her the resilience she needed. “Antidepressants often just felt like a palliative care approach to mental health,” she says. In comparison, “the psilocybin trial gave me the tools to begin that work and build that emotional resilience.”

“While studies for somebody who is facing death and depressed due to terminal illness may show a lasting change from one session with psilocybin, if someone has been depressed for decades for no discernible reason, it is less likely to be alleviated with just one or two doses,” Watts notes.

When the trial ended in March 2020, as the COVID-19 pandemic was exploding, Watts and other members of the team set up online therapy sessions for trial participants who felt they needed extra support. Schneider was quick to sign up, as was Thorne, along with 16 other participants who have met regularly with the study psychologists and one another online for a year. This has extended the period known as “integration,” when individuals make sense of the visions and insights they felt under the influence of psilocybin.

“People describe psychedelic therapy as 25 years of therapy in one afternoon. And it can absolutely feel like that, but it’s not a silver bullet—and it’s just an afternoon,” Schneider says. “The real magic in this is not in the dosing day, it’s in the work that you do afterward.”

*From the article here :

Psilocybin Therapy May Work as Well as Common Antidepressant

For the first time, a randomized controlled trial shows the psychedelic offers potent, if short-term, relief in comparison with an SSRI

www.scientificamerican.com

 

[mr peabody]

Patients with ailments ranging from depression and anxiety to alcohol or nicotine addiction
could benefit from the ongoing resurgence of psychedelic treatments.

Psychedelic Therapies for Depression

by Malosree Maitra | McGill University | Neuroscience News | 6 Apr 2021

As interest in using psychedelics to treat a range of mental health disorders grows, researchers consider the impact and therapeutic benefits of using psychedelics to help alleviate symptoms of depression.

When you hear the word “psychedelic” your first mental picture may be of someone experiencing intense hallucinations, but perhaps that’s about to change. In addition to being potent hallucinogens, psychedelics are now competing for the spot of the next miracle cure for various mental health conditions. In particular, psychedelics have been in the news in Canada, where terminal patients have been granted exemptions to use psychedelics for anxiety and the benefits and pitfalls of psychedelics in psychiatry are being debated.

Patients with ailments ranging from depression and anxiety to alcohol or nicotine addiction could benefit from the ongoing resurgence of psychedelic treatments. Scientists have been studying the therapeutic properties of psychedelics at least since the 1960s. These investigations were subsequently impeded for several decades by government prohibitions on the use of these compounds, but the
research landscape has evolved considerably in recent years.

Psychedelics come in many forms. Ayahuasca is a plant extract consumed during indigenous rituals in South America. Psilocybin is one of the active ingredients of magic mushrooms. LSD, of course, is the infamous party drug popular at raves. All three are currently being investigated as therapeutics in clinical trials.

Therapeutic use of psychedelics involves “psychedelic assisted psychotherapy” wherein a patient is given a hallucinogen to trigger a “mystical experience” while being closely monitored in a controlled setting. David Nutt’s lab at the Imperial College London and Roland Griffiths’ lab at Johns Hopkins University contributed several of the early results demonstrating the antidepressant potential of
psilocybin.

Encouragingly, in these small clinical studies, on patients with severe depression or depression stemming from life-threatening illness, just one or two treatment sessions had immediate and lasting therapeutic effects for weeks or even months.

Psilocybin could decrease symptoms in as little as 24 hours, compared to the 4- to 6- week timeline for the therapeutic effects of conventional antidepressants such as Prozac. This speed of action is certainly enticing. Psychedelic therapy holds even more promise since around a third of depressed patients do not respond to conventional antidepressants.

Since 2018, the US Food and Drug Administration and the European Medicines Agency have prioritized clinical trials of psilocybin treatment for depression. In this time period, several studies have been completed or are ongoing. Many of the studies are employing neuroimaging to explore the associated brain changes. Importantly, several upcoming trials aim to include up to hundreds of participants, such as those conducted by COMPASS Pathways and the Usona Institute.

The Canadian chapter of the Multidisciplinary Association for Psychedelic Studies reports that since 2020, research into and application of psychedelic therapies has made great strides forward. Particularly, Health Canada granted exemptions for psilocybin assisted psychotherapy in several instances, mostly to alleviate depression and anxiety in terminal patients.

Although the use of psychedelics in medicine is still strictly regulated, several health care professionals were given permission to possess and test psilocybin for medical purposes.

here are fewer clinical studies of ayahuasca and LSD in depression, but interest is slowly increasing. For ayahuasca several small, early studies from researchers in Brazil reported improvements in depressive symptoms, whereas for LSD, an ongoing trial in Switzerland is set to test 60 participants by 2023.

The rising number of studies is seeking to address some important unanswered remaining questions: Which doses and protocols are most effective and safest? What is the most appropriate placebo for psychedelic trials? What are the potential long-term side-effects, if any?

The detailed mechanisms by which psychedelics can decrease anxiety and depression are as yet only hypothesized. One possible mechanism, is the activation of the serotonin neurotransmitter system in the brain. Most of us think of serotonin as a modulator of mood, one of the “happy hormones”. Many conventional antidepressants can also affect the serotonin system, which makes this a plausible mechanism.

There are also concerns about the side-effects of psychedelics, including transiently increased anxiety and paranoia and the potential for abuse of power in psychedelic assisted therapy, given the vulnerability of patients during induced hallucinations. However, conventional antidepressants are also
rife with side-effects including altered sleep, altered appetite, and sexual dysfunction.

Even if the psychedelics are speedily approved for treating depression, they will likely be reserved for those with severe, treatment-resistant depression, similar to other second-line treatments such as ketamine or electroconvulsive therapy. But, given the many limitations of conventional antidepressants, it could be a highly beneficial to many patients if further clinical research on psychedelic therapies is pursued and funded.

*From the article here :

Resurging Psychedelic Therapies for Depression - Neuroscience News

As interest in using psychedelics to treat a range of mental health disorders grows, researchers consider the impact and therapeutic benefits of using psychedelics to help alleviate symptoms of depression.

neurosciencenews.com

 

[mr peabody]

‘When taken in high doses, psilocybin profoundly alters the quality of conscious awareness,
releasing suppressed memories and feelings.’

Psychedelics are transforming the way we understand depression and its treatment

by Robin Carhart-Harris | The Guardian | 20 Apr 2021

Psychiatry has long failed to explain depression. Our research into psilocybin suggests a new approach could offer answers.

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 $15bn (£11bn). 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 around 50-60%. Other limitations of SSRIs include poor compliance, symptoms when people stop taking them, unpleasant side-effects and a sluggish onset of antidepressant effects.

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%. 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%.

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.

Robin Carhart-Harris

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 $15m (£8.5m) 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.​

• Robin Carhart-Harris is head of the Centre for Psychedelic Research at Imperial College London
• In the UK, the charity Mind is available on 0300 123 3393 and Childline on 0800 1111.
• In the US, Mental Health America is available on 800-273-8255.
• In Australia, support is available at Beyond Blue on 1300 22 4636, Lifeline on 13 11 14, and at MensLine on 1300 789 978

Psychedelics are transforming the way we understand depression and its treatment | Robin Carhart-Harris

Psychiatry has long failed to explain depression. Our research into psilocybin suggests a new approach, says researcher Robin Carhart-Harris

www.theguardian.com

 

[mr peabody]

Centers for Disease Control and Prevention

Ketamine's effects on depression identified in new study

by Timothy Huzar | Medical News Today | 9 June 2020

A new study has identified how ketamine combats difficult-to-treat depression.

New research has revealed the specific parts of the brain that ketamine affects when doctors use it to treat people with difficult-to-treat depression.

The study, which appears in the journal Translational Psychiatry, may open the door to new therapies in the treatment of depression.

According to the CDC, in the United States, about 8% of people over the age of 12 have depression during any 2-week period. The CDC describe depression as a sad mood that extends for a long period and affects a person’s ability to live a normal life.

When severe, depression can have a serious negative effect on a person’s life, sometimes leading to suicidal thoughts.

Experts do not fully understand why some people experience depression, although the National Institute of Mental Health suggest that genetic, environmental, biological, and psychological factors may play a role. It is treatable with medication, psychological therapy, or a combination of the two.

Previous research has made it clear that the drug ketamine can be an effective antidepressant, and some scientists have proposed it as a treatment in cases of depression that do not respond to conventional treatments.

However, precisely how and why ketamine functions as an antidepressant is less clear. As a consequence, the authors of the present study wanted to identify precisely what effects ketamine has on the brain of a person who is not responding to conventional treatments. They hope that this research may lead to better treatment options for these individuals.

Suicide prevention

If you know someone who is at immediate risk of self-harm, suicide, or hurting another person:

1. Ask the tough question: “Are you considering suicide?”

2. Listen to the person without judgment.

3. Call 911 or the local emergency number, or text TALK to 741741 to communicate with a trained crisis counselor.

4. Stay with the person until professional help arrives.

5. Try to remove any weapons, medications, or other potentially harmful objects.

If you or someone you know is having thoughts of suicide, a prevention hotline can help. The National Suicide Prevention Lifeline is available 24 hours per day at 800-273-8255. During a crisis, people who are hard of hearing can call 800-799-4889.

Click here for more links and local resources.

Looking at ketamine’s effects in the brain

To do this, the researchers gave participants doses of ketamine that were low enough not to have an anesthetic effect and then took images of their brains using a positron emission tomography (PET) camera.

According to the study’s first author, Dr. Mikael Tiger, a researcher at the Department of Clinical Neuroscience at the Karolinska Institutet in Solna, Sweden, “In this, the largest PET study of its kind in the world, we wanted to look at not only the magnitude of the effect but also if ketamine acts via serotonin 1B receptors.”

“We and another research team were previously able to show a low density of serotonin 1B receptors in the brains of people with depression.”

By using a radioactive marker that binds to a person’s serotonin receptors, the PET images could highlight what effects ketamine was having on these receptors, which play a crucial role in depression by modulating the amount of serotonin that a person receives. Experts believe that low levels of serotonin correlate to more severe experiences of depression.

The authors of the study recruited people through internet advertising. After receiving 832 volunteers, the authors reduced this number to 30 to make sure that the participants were as relevant to the study as possible.

Other than having major depressive disorder (MDD), the participants were healthy. They had not responded to previous treatment for MDD.

The researchers split the participants into two groups, treating 20 people with ketamine and the other 10 with a placebo.

The study was a randomized, double-blind, placebo-controlled study, meaning that neither the doctors nor the participants initially knew to which group each participant belonged.

Prior to the treatment, the researchers took a baseline scan of the participants’ brains. They took a second scan in the days following the treatment.

For the second phase of the study, 29 of the participants agreed to take ketamine twice a week for 2 weeks.

Serotonin reduced, dopamine increased

Using a rating scale for depression, the researchers found that 70% of the participants in the second phase of the study responded to the ketamine.

Furthermore, after analyzing the PET images, the authors found that the ketamine was affecting the participants’ brains in a previously unidentified manner, reducing the output of serotonin but increasing the output of dopamine, which is also important for mood regulation.

According to the last author of the study, Dr. Johan Lundberg, research group leader at the Department of Clinical Neuroscience, Karolinska Institutet, “We show for the first time that ketamine treatment increases the number of serotonin 1B receptors.”

“Ketamine has the advantage of being very rapid-acting, but at the same time, it is a narcotic-classed drug that can lead to addiction. So it’ll be interesting to examine in future studies if this receptor can be a target for new, effective drugs that don’t have the adverse effects of ketamine.” - Dr. Johan Lundberg

Ketamine's effects on depression identified in new study

Ketamine can improve symptoms of depression in people who do not respond to other treatments, but how does it work? A new study investigates.

www.medicalnewstoday.com

 

[mr peabody]

Sgt. Pepper

Microdosing for Depression

Is microdosing helpful for treating depression? Join Dr. Erica Zelfand as we explore healing depression through psychedelic medicine.

by Erica Zelfand, ND | Psychedelic.Support | 22 Apr 2021

Matias’s appointment fell on Valentine’s Day that year. During the visit, he stared at the wall behind my head and admitted he had been having “those thoughts” again. That is to say, our code for suicidal ideation.

Matias had tried many things to get relief from his major depressive disorder (MDD). This included too many pharmaceutical antidepressants to list here, a couple of anti-psychotic medications, a beta blocker, an intensive outpatient program (IOP) at the local hospital, and weekly therapy. The medications made him feel “foggy” more than calm. Nor did they do much to change his PHQ-9 depression scores. Meanwhile, it didn’t help that today was a holiday that celebrated romantic, partnered love. Thus highlighting Matias’ single status. Matias felt at the end of his rope.

Just a few days later, however, Matias sent me this message: “This is the best I have felt in months. Could one drop really have such an effect?” He went on to explain that at the suggestion of a friend, he had taken a microdose of LSD. A 10 microgram dose to be precise.

So, Matias isn’t the only person who has turned to microdosing in the hope of getting relief from a mood disorder. A 2018 study [1] of 1,102 people who had microdosed found that 40% of them did it specifically to try and improve their mental health. A 2020 survey [2] found that 44% of those microdosing psilocybin or LSD for mental health reasons reported their mental health was much better. (Twenty one percent of these individuals started microdosing to help their depression, and 7% were doing it for anxiety).

Microdosing for depression, self-reported success

Most of the studies on microdosing are based on surveys completed online by individuals who have tried microdosing themselves. While this method of research is by no means the scientific gold standard of the double blind, controlled randomized trial we like to see in drug research, it still allows us to understand people’s motivations for trying microdosing and their perceived results.

Nonetheless, based on these self-report studies, many people who try microdosing say they notice significant improvements in their mood [3] with reports of less perceived depression, lower stress levels, decreased trauma triggering, and improved energy and focus [4],[5],[6].

While we cannot say for certain that microdosing helps with depression, the data currently available certainly implies that low doses of psilocybin and LSD may indeed help in some cases.

Does microdosing work better than conventional prescription antidepressants?

But is microdosing as effective as conventional pharmaceutical antidepressant drugs like fluoxetine (Prozac) in the treatment of mental health disorders? Yes – according to one small 2019 study [7]. In this study, individuals age 18 and up completed an online questionnaire focusing on mental health and answered questions about the various treatments they’d tried in the past and how well (or poorly) they worked.

Of the people who completed the questionnaire, 7 percent (or 410 individuals) had a diagnosis or one or more mental health and/or physiological disorders. (*A physiological disorder is an illness that interferes with the normal, healthy functions of the body. Examples of physiological conditions include diabetes, asthma, Parkinson’s, cancer, and rheumatoid arthritis.) Their responses showed a clear pattern: these people felt that microdosing had worked significantly better than conventional prescription medications for a variety of health conditions, including depression, ADD/ADHD, and anxiety disorders.

In the case of Matias, a number of his friends had told him that they didn’t think his prescription medications were helping. They gently told him that he didn’t seem any happier or functional. He seemed “flat and spacey” on the other hand and suggested he mention it to his prescriber. After two weeks of microdosing, however, Matias felt energetic enough to meet up with these same friends for a picnic. During the meal, his best friend commented that Matias seemed better that day. “I’ve been trying microdosing,” Matias confessed. “It’s working, bro, keep going,” his friend replied, “I feel like I’m catching a glimpse of the Matias I used to know, of the guy you were before.”

An unexpected microdosing perk

Another perk of microdosing is that it seems to combine safely with most other psychiatric medications – meaning that individuals do not have to stop their antidepressant or anxiolytic medications before they give microdosing a try (the one possible exception being lithium) [8]. Furthermore, people often report that after a few months of microdosing they are able to easily taper down to lower doses of their pharmaceutical antidepressant and anxiolytic medications – or wean off them entirely.

That’s exactly what happened with Matias. He gradually weaned off of all psychiatric prescription medications within a few months of starting microdosing (with the support of his prescriber). So now he’s grateful to be free of those pesky side effects and the plastic pill organizer that used to sit on his kitchen counter.

Does microdosing work better than larger psychedelic doses?

How does microdosing psychedelics measure up against taking higher, trip-inducing macrodoses of psilocybin or LSD? Again, the answer is not yet clear, but according to the reports of 410 people analyzed in a 2019 survey,[9] it depends on the condition. Microdosing and macrodosing seem to work about as well in treating physiological disorders (physical ailments).

When it comes to psychological conditions, however, people reported that macrodosing helped them more significantly than microdosing. Most importantly, this may be on account of the mystical experience element seen with psychedelic trips that is absent in the microdosing experience. In controlled clinical trials of depression, the degree of the mystical experience was related to depression symptom improvement.

After microdosing for a few months, Matias took a break. Then he noticed that after about 10 days he started “slipping” back into some of his old, dark ways of thinking – and his PHQ-9 depression scores reflected this. He joined his friends for a day on the beach, during which time the group ate psilocybin-containing mushrooms. Matias tells me that his trip on 3 grams of dried fungus that day was both challenging and beautiful. Moreover, he described the experience as “spiritual.” Whereas Matias used to constantly think about suicide, he reports that since his trip, “I think about it sometimes, but then I’m like, ‘Nah, no way am I actually gonna do that.’”

Microdosing for depression, in summary

There is a lot we do not know about microdosing psychedelics. The little we do know comes mainly from people’s reports about their subjective experiences. Based on that limited information, it seems that microdoses of psilocybin and LSD:​

• Can likely be taken concurrently with conventional pharmaceutical antidepressants (with the potential exception of lithium);​
• May help people gradually taper down their use of conventional medications;​
• Maybe more effective than conventional pharmaceuticals in the treatment of depression, anxiety, ADD/ADHD, and other conditions;​
• May work just as well as psychedelic macrodoses in the treatment of physiological conditions; and​
• Might not be quite as effective as macrodoses (psychedelic trips with mystical experiences) in the treatment of psychological conditions like depression.​

As always, it’s important to weigh the risks and benefits of any new medical intervention – especially one that has yet to undergo rigorous controlled studies. But based on these initial findings, we are seeing an upsurge in studies being planned to evaluate microdosing for mood disorders.

Microdosing for Depression: Better than Prozac? Better than Tripping?

Is microdosing helpful for treating depression? Join Dr. Erica Zelfand as we explore healing depression through psychedelic medicine.

psychedelic.support

 

[mr peabody]

Could DMT sweep existing treatments for depression aside?

Psychedelic News Wire | 19 Jul 2021​

Since research on psychedelics was revived in the 2000s, prompted by the easing of the regulations that govern the substances, a lot of studies have shown that drugs such as LSD and psilocybin possess great therapeutic potential and can be used to treat conditions such as depression, anxiety and addiction.

These discoveries have led to the creation of companies that are focused on psychedelic therapy and that are working on finding ways in which these substances can be used in lieu of conventional medicine.

Among these companies is Small Pharma, a neuropharmaceutical firm based in the United Kingdom, which is carrying out the first clinical trial globally on DMT. The company’s main objective is to uncover whether the substance can help treat major depressive disorder.

This research could shift the focus away from selective serotonin reuptake inhibitors, which are currently used as antidepressants, towards psychedelics’ healing powers as well as revolutionize how professionals in the field of mental health approach therapy. The company’s chief scientific and medical officer Dr. Carol Routledge stated in an interview that she believes DMT-assisted psychotherapy may be among the best treatments in existence.

DMT is a chemical that occurs naturally and can be found in many animals and plants. Humans are known to produce DMT in the brain. The chemical, which is medically known as N, N-dimethyltryptamine, acts on the serotonin receptors in the brain, which leads to strong perceptual and emotional changes. The hallucinogenic induces intense psychedelic experiences in a matter of seconds after it has been ingested, with its effects only lasting a few minutes.

DMT’s psychological effects do not decrease with repeated dosing, with researchers finding that individuals who ingest the drug do not develop a tolerance for it.
Small Pharma started its first phase of the trial in February of this year, and the company will focus on exploring the effects of DMT-assisted therapy on healthy participants who have never ingested psychedelics. After the completion of the first phase, the company will begin the second phase of the trial, which will include enrolling participants who suffer from major depressive disorder.

Researchers note that while standard treatments such as SSRIs help stabilize patient moods, they don’t tackle the psychological issues that bring about depression or help every patient who uses them, which is where DMT comes in. DMT may, apart from fixing the underlying psychological issues that contribute to various mental health conditions, also have long-lasting psychological benefits for patients.

Scientists have found that the hallucinogen, just like other psychedelics, breaks the negative thought-pattern pathways that are common in mental health conditions and increases synaptic connectivity as well as neuronal connectivity.

The medical potential of DMT has encouraged many entities such as XPhyto Therapeutics Inc to allocate significant amounts of resources to research the different medicinal applications to which this psychedelic compound can be put.

Could DMT Sweep Existing Treatments for Depression Aside? - PsychedelicNewsWire (PNW)

Since research on psychedelics was revived in the 2000s, prompted by the easing of the regulations that govern the substances, a lot of studies have shown that drugs such as LSD and psilocybin possess great therapeutic potential and can be used to treat conditions such as depression, anxiety and...

www.psychedelicnewswire.com

 

[mr peabody]

Ayahuasca relieves Depression and Anxiety, study*

Although classified as a Schedule I drug, recent research suggests it has medical value.

by Tibi Puiu | ZME Science | 30 Jun 2021

Ayahuasca is a powerful hallucinogenic tea that has been brewed in the Amazon rainforest for thousands of years. Although the brew’s main active ingredient, dimethyltryptamine (DMT), is illegal in most countries, recent research suggests the drug may have significant therapeutic properties in the context of improving depression and anxiety symptoms. A new study published this week — the largest thus far on ayahuasca — adds weight to this body of evidence.

The Global Ayahuasca Project was conducted between 2017 and 2020 and involved more than 11,000 individuals, 7,785 of whom suffered from symptoms of depression or anxiety at the time they took the drug. The participants had to fill an online self-reported questionnaire designed to measure mental health outcomes among Ayahuasca users.

The results were impressive, to say the least. Nearly 94% of the respondents experienced at least some sort of improvement in their depression symptoms, ranging from “a bit” and “great” to the complete resolution of their depression. The same was reported in 90% of cases for anxiety symptoms.

Users who reported profound mystical experiences tended to report the greatest improvements in their depression or anxiety symptoms. Similarly, insights into one’s personal relationships following Ayahuasca use were also correlated with improved mental health outcomes.

However, a small fraction actually saw their mental health deteriorate following Ayahuasca use. About 2.7% of respondents reported worsened depression symptoms and 4.4% reported worsened anxiety symptoms. The researchers found that feeling lonely, nervous, anxious or on edge, as well as depressed or hopeless in the weeks immediately following Ayahuasca consumption were predictors of worsened symptoms.
​

“Drinkers of Ayahuasca in naturalistic settings perceived remarkable benefits for their affective symptoms in this survey assessment. There is no obvious evidence of negative mental health effects being associated with long-term consumption. Additional randomized controlled trial evidence is required to establish the efficacy of Ayahuasca in affective disorders, and to understand the worsened symptoms reported by a small percentage of drinkers,” the authors of the study wrote in the Journal of Affective Disorders Reports.​

The fact that this cross-sectional study relied on self-reported data is an important limitation. Also, the study relied on reaching out to Ayahuasca users on niche forums and websites, where individuals with positive experiences are more likely to be online and respond, thus contributing to selection bias to some degree. However, the very large sample size makes it a valuable study. It’s not alone either.

Ayahuasca and mental health

Traditionally, ayahuasca is made by brewing the Banisteriopsis caapi vine and the Psychotria viridis shrub, along with other native plants, in a specific manner. When ingested, the brew delivers a powerful dose of DMT to the body. Typically, a DMT trip shouldn’t last more than a couple of minutes but thanks to the presence of at least one monoamine oxidase-inhibiting plant, the DMT can bind to receptors in the brain for hours. The experience has been described as anything between enlightening to downright distressing.

The brew contains several substances that alter brain chemistry. Among them, some regulate the neurotransmitters serotonin and MAO-A. It was also previously shown that ayahuasca directly affects activity in the hippocampus and amygdala, areas of the brain responsible for memory and emotions, respectively.

A 2013 study carried out by researchers led by Gerald Thomas from the University of Victoria in Canada, found that ayahuasca therapy causes significant improvements “for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales.” Thomas argues that ayahuasca therapy is particularly helpful for those suffering from psychological trauma, which puts them at risk of developing alcohol and other drug addictions.

A study published in 2020 by neuroscientists at the University of California, San Francisco, scanned the brains of 50 healthy participants the day before and after they received either a single low dose of Ayahuasca or a placebo. According to the researchers, “the psychedelic experience induced by ayahuasca has a long-lasting effect on the functional organization of brain networks supporting higher-order cognitive and affective functions.”

Changes in these neural networks are associated with introspection, altered levels of affect, and motivation, which may explain both the altered states of consciousness during the high of the drug and the long-lasting brain changes elicited by ayahuasca.

As Ayahuasca’s potential medical benefits surface, scientists will hopefully be allowed to perform clinical trials with the drug. Decades after it was banned from research by governments, studies may show that Ayahuasca’s benefits far-outweigh its risks in a controlled medical context.

*From the article here :

Ayahuasca relieves depression and anxiety, finds study on nearly 12,000 users

Although Ayahuasca is classified as a Schedule I drug, recent research suggests it has medical value.

www.zmescience.com

 

[mr peabody]

Is DMT the best new treatment for depression?

By Stephen Johnson | Freethink | 10 Jul 2021

Psychedelic therapy could bring the ancient healing powers of drugs like DMT into mental health clinics.

Psychedelic therapy is slowly but surely inching its way toward mainstream medicine. Since the U.S. and other nations began easing regulations on psychedelic research in the 2000s, studies have shown that drugs like psilocybin and LSD seem effective at treating conditions like addiction, anxiety, and depression.

Now, a U.K.-based neuropharmaceutical company — Small Pharma — is conducting the world’s first clinical trials exploring whether DMT can treat major depressive disorder. The research could transform how mental health professionals approach therapy, shifting the focus away from SSRIs and toward the healing powers of psychedelic experiences.

“DMT-assisted psychotherapy could actually be one of the best treatments ever,” Dr. Carol Routledge, chief medical and scientific officer at Small Pharma, told Freethink. “I really, really genuinely believe that, and I don’t say that lightly.”

Psychedelic therapy is a pioneering field. But in some ways, the field’s recent findings can be viewed as ancient knowledge rediscovered.

The interesting origins of psychedelic therapy

In South America and Africa, native tribes have ingested psychedelics as part of religious practices for millennia. Research suggests the history of hallucinogen use stretches back to 1,000 B.C., possibly much earlier.

The shamans who administered these substances seemed to be experts in psychedelic botanology, able to identify and combine various barks, vines, and leaves to create powerful hallucinogenic concoctions, like ayahuasca, whose main psychoactive component is DMT.

For the natives who consumed psychedelics, the line between spiritual practice and medicine was blurry. Most seemed to view the plants not merely as drugs but as entities to consult, or portals to another dimension. “They carry you there where God is,” tribespeople in the southern Mexican mountains told the author Robert Gordon Wasson in the 1950s.

The 20th century brought psychedelics into the scientific realm. In the decades after Albert Hofmann first experimented with LSD in 1943, researchers conducted hundreds of studies exploring the therapeutic potential of psychedelics. By the 1960s, it’s estimated that tens of thousands of people took drugs like LSD and psilocybin as part of psychedelic therapy and research.

The experiences reported in the early days of psychedelic research sometimes had the same religious overtones that natives had long described. In one of the first experiments involving DMT in 1958, a 27-year-old female participant reported:

“The whistling has stopped; I have arrived. In front of me are two quiet, sunlit Gods. They gaze at me and nod in a friendly manner. I think they are welcoming me into this new world.”

The results of early psychedelic research were promising. A 2016 meta-analysis of 19 studies that used psychedelics to treat mood disorders between 1949 and 1973 found that 79% of participants showed “clinically judged improvement.”

But amid tectonic shifts in culture and medicine in the mid-20th century, psychedelics began to take on a suspicious New Age veneer in the public consciousness. It didn’t help that the drugs weren’t always researched or consumed responsibly.

By the 1960s, LSD had become popular in the American counterculture movement, thanks in part to figures like the psychologist-turned-guru Timothy Leary who once said, “To learn how to use your head, you have to go out of your mind.”
​

“To learn how to use your head, you have to go out of your mind.” - Timothy Leary​

The media often covered psychedelics from a sensationalistic perspective. This frustrated some psychedelic researchers, partly because people were suddenly hesitant to participate in experiments. In 1968, Charles C. Dahlberg, an American doctor who received a grant from the National Institute of Mental Health to study LSD, wrote:

“Mass communications concerned with the effects of drug use have primarily relied upon emotional rather than rational appeals, and have associated LSD use with mental illness, crime, mass orgies, and the like.”

The U.S. made it illegal to possess LSD in 1968. In 1970, Congress passed the Controlled Substances Act, which classified psychedelics as having “no recognized medicinal value.” The United Nations also passed a treaty banning psychedelics in 1971. Facing tougher restrictions and dwindling funding, global psychedelic research slowed to a crawl.

But in the 2000s, the field revived in part because emerging brain-imaging technologies allowed scientists to study psychedelics from a new angle. In 2014, the editors of Scientific American published the op-ed, End the Ban on Psychoactive Drug Research, which argued that: “new thinking is desperately needed to aid the estimated 14 million American adults who suffer from severe mental illness.”

Today, psychedelics remain controlled substances under federal law. But the U.S. Food and Drug Administration has been approving more psychedelic research in recent years, as privately funded studies steadily show the drugs may treat some mental illnesses more effectively than conventional medicine. In some cases, a single dose of a psychedelic can generate months-long therapeutic benefits.

Compared to LSD, MDMA, and psilocybin, DMT and its potential in psychedelic therapy remain little understood. But early data suggests that the world’s most powerful hallucinogen may also have outsized effects on depression.

Experiencing the fifth dimension

What is DMT? Medically known as N, N-dimethyltryptamine, DMT is a naturally occurring chemical found in many plants and animals. Humans also produce DMT in the brain. Like all tryptamine drugs, DMT acts on the brain’s serotonin receptors, which causes strong emotional and perceptual changes.

Unlike other hallucinogenic drugs though, DMT delivers intense psychedelic experiences within seconds of ingestion and the effects last only a few minutes. People who ingest DMT don’t develop a tolerance, and the drug’s psychological effects don’t diminish with repeated dosing.

Is DMT the best new treatment for depression?

Psychedelic therapy could bring the ancient healing powers of drugs like DMT into mental health clinics.

www.freethink.com

 

[mr peabody]

Aquilino Cancer Center in Rockville, Maryland

Psilocybin Therapy for depression in cancer patients, study*

Psilocybin Alpha | 20 Oct 2021

COMPASS Pathways, a mental health care company dedicated to accelerating patient access to evidence-based innovation in mental health, welcomed the topline data shared today from an open-label study of psilocybin therapy for depression in cancer patients. Within one week of a single administration of COMP360 psilocybin therapy, 50% of participants achieved remission in depression symptoms, which was sustained for the eight week follow-up period.

This investigator-initiated feasibility study was conducted by Maryland Oncology Hematology at the Aquilino Cancer Center in Rockville, Maryland, USA. It was an open-label study involving 30 patients with cancer diagnosis and major depressive disorder (MDD), all of whom completed the study. Half of the participants had previously been treated for their current episode of depression with antidepressants and all were receiving active treatment for cancer; 19 participants had no previous experience with psychedelic substances. Patients were given a 25mg dose of COMP360 psilocybin in conjunction with psychological support from specially trained therapists, following the COMP360 psilocybin therapy protocol. Unlike earlier psilocybin therapy trials for depression in cancer, this study was not restricted to patients with late-stage cancer. The Maryland team also pioneered simultaneous group administration in a cancer care centre, with two to four patients being given psilocybin at the same time, with 1:1 therapist support. This tested the value of group support for cancer patients as well as the potential for increased scalability in providing psilocybin therapy in real world settings.

COMP360 psilocybin therapy was found to be generally well tolerated with no treatment-related serious adverse events. Adverse effects seen on the day of dosing were as expected from experience in healthy volunteer groups and included headache, changes in sensory perception and mood alteration.

Patients were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), a clinician-administered symptom questionnaire. A sustained response rate (a decrease of ≥50% in the MADRS score from baseline observed at any visit up to and including week 3, and also fulfilled at week 8 was seen by 24 patients; 15 patients showed remission of depression symptoms (a MADRS score <10) one week after a single dose of psilocybin, which was sustained up to eight weeks. The 30 patients in the study began with an average MADRS score of 25.9, representing moderate depression. After psilocybin therapy, the average score dropped by 19.1 points. The study investigators noted that this was an open-label study in which neither patients nor raters were blinded, so there is a significant risk that the results incorporate a large expectancy bias.

Dr Manish Agrawal, medical oncologist, Co-director of Clinical Research at the Aquilino Cancer Center, and the trial’s Principal Investigator, said: “A cancer diagnosis can change the course of a patient’s life. For complete cancer care, we need to focus on whole-person healing and include the mental wellbeing of our patients. This is not widely addressed today, but it’s time to do something about it. These study results have shown that psilocybin therapy may be helpful with MDD in cancer, and we look forward to doing further analysis and following up with additional studies. While it’s premature to draw any definitive conclusions from this study, simultaneous administration appears to be well tolerated and feasible, and the results are promising and worthy of further research.”

Professor Guy Goodwin, Chief Medical Officer, COMPASS Pathways, said: “These preliminary findings suggest COMP360 psilocybin therapy was well tolerated by cancer patients with major depressive disorder. It is promising to see that this may be a feasible fast-acting therapy for depressed patients with a significant physical co-morbidity. This would certainly be welcome in conditions where depression is difficult to treat in a timely way.”

Professor Goodwin added: “This open-label MDD study is very different from the randomised, controlled, double-blinded phase IIb study that COMPASS has conducted for patients with treatment-resistant depression. Nevertheless, it has given a positive signal of the potential for COMP360 psilocybin therapy, and we are delighted to see that a number of patients showed signs of improvement. We are now considering how we take this forward with future studies as we continue to develop a broad portfolio of therapies in areas of significant unmet need in mental health care.“

*From the article here :

Open-label study of COMP360 psilocybin therapy for depression in cancer patients demonstrates feasibility of simultaneous psilocybin administration in small groups - Psilocybin Alpha

Investigator-initiated study shows remission in major depression symptoms for 50% of participants London, UK – 20 October 2021 COMPASS Pathways plc (Nasdaq: CMPS) (“COMPASS”), a mental health care…

psilocybinalpha.com

 

[mr peabody]

I use ketamine for depression – Here’s how it works

by Doug Dais | Freethink

Ketamine’s reputation is moving away from “party drug” and into one of the newest and most effective forms of depression treatment.

When first manufactured as an anesthetic for humans and animals in 1962, doctors certainly had no intention of prescribing ketamine for depression. Nor did they intend for its psychoactive effects to boost its popularity among festival-goers and galaxy explorers.

The surprising and powerful effect that ketamine has proven to have on the brain’s neurons though, has led doctors to explore its medical potential and begin to strip away the stigma that decades of recreational abuse have given to a potentially life-saving treatment.

From party drug to life-saving treatment

Ketamine has gained notoriety over the past few decades as a mind-altering drug capable of both anesthetizing horses and sending party-goers into hallucinogenic bliss. The drug has a long and storied history in the club scene and due to its abuse in this scene, it became discredited and stigmatized.

Once drugs are scandalized to this extent it’s difficult to highlight the positive neurological and psychoactive effects of which they’re capable. But doctors such as Dr. Dennis Charney, of the Icahn School of Medicine at Mount Sinai, are finding that ketamine has incredible potential when used as a means of treating various forms of mental illness.

Dr. Charney recognized an alternate potential for ketamine and created an entirely new field of science called suicide biology. He jumped on the opportunity to harness the drug’s effects to address the country’s rapidly growing issues of depression and suicide.

Because of the research of Dr. Charney and others, ketamine’s reputation is now moving away from that of a party drug and into one of the newest and most effective forms of medication to treat severe depression.

Ketamine for depression: How it works

What differentiates ketamine from other antidepressants is how it works to affect the brain. Antidepressants typically focus on increasing chemicals in the brain such as serotonin and dopamine.

Using ketamine for depression, however, can actually assist in repairing neuron synapses that typically don’t function properly in the brains of depressed patients. Ketamine provokes a response in the brain, and it’s the adaptation to that provocation- the regrowth of synaptic connections- that is responsible for the rapid improvement in the mood it creates.

The need for an alternative treatment

Depression is an ever-growing epidemic in America and it’s one that requires outside-of-the box thinking, such as the introduction of ketamine therapy. An NBC article reports that since 2013, diagnoses of major depression have risen by 33%, including a 47% increase in those ages 18 to 34.

The exponential growth of this affliction, despite the large number of chemical antidepressants currently available, indicates that there is an enormous need and opportunity for alternative treatments like using ketamine for depression.
​

"I was suicidal with a plan, and ketamine stopped that in it's tracks. After the 3rd infusion I was getting in tickle fights with my husband. I can't believe how fast I've been getting better and happy and thinking about goals." -Sheen Hunter​

One of the major issues with today’s well known and more socially-accepted forms of antidepressants is their ineffectiveness on a growing number of individuals. Around five million people in the U.S. with depression don’t respond to commonly prescribed or recommended treatments.

This condition is known as Treatment-Resistant Depression. The hopeless feeling that these individuals experience is compounded by the bombardment of prescribed but ineffective treatments. The crushing weight of doom they carry is further impacted by the feeling that nothing is going to be able to help them unload this burden.

It’s no wonder then that, as Bloomberg Businessweek reports, the rate of suicides in our country rose by 30% between 1999 to 2016 alone. Additionally, suicide is now the second-leading cause of death for Americans ages 10 to 34.

Ketamine infusion and nasal sprays

Ketamine infusion therapy is one of the newest and most effective ways that doctors are able to provide relief for individuals with severe depression. Infusion centers are beginning to pop up all over the country, which is making the treatment more accepted and accessible.

Patients interested in trying ketamine for depression can visit these centers once every one to six months depending on the severity of their condition. Within several hours of treatment many patients begin to feel better, and within 24 hours some feel nearly or completely better.

People with Treatment-Resistant Depression who start taking prescription antidepressants typically have between a 10 and 20 percent chance of a positive response. Those being treated with ketamine infusions have a positive response rate between 50 and 80 percent.
​

Ketamine can actually assist in repairing neuron synapses that don’t function properly in depressed patients.​

These staggering and positive results have been known to the scientific and medical communities for many years, but ketamine’s “party drug” stigma hindered further research and adoption. The good news is that now, attitudes toward the drug are finally starting to change and with the changes, access to ketamine as a medication is becoming more readily available.

As both society and the medical community begin to gain a different perspective on ketamine, new research findings continue to expand the drug’s possibilities. The FDA approved a nasal spray form of the drug last year which can be used in addition to ketamine infusion.

The spray allows users to get relief in minutes or hours, rather than weeks or months like typical antidepressants. Providing those with severe depression fast-acting, at-home relief is incredibly important as the country fights to reverse high suicide rates.

New promise for ketamine and depression

The recent growth of research has also expanded the scope of ketamine’s potential for those dealing with PTSD, severe anxiety, chronic pain, OCD, and bipolar disorder, offering new hope for individuals who have felt hopeless for too long.

Like with any drug, ketamine’s effects can be dangerous and abused if it’s used improperly and for non-medical purposes. It’s equally important though to weigh the exponential impact that ketamine could have for those who suffer from mental illness, and it would be negligent to not continue the expansion of research of this drug.

Time is rarely on the side of those suffering with a severe mental illness, but the fast-acting potential of ketamine might just be able to reverse the clock on depression rates and erase the drug’s negative stigma.

I use ketamine for depression - here’s how it works

From party drug to life-saving treatment, doctors are now prescribing ketamine for depression in patients who don’t respond to typical medications.

www.freethink.com

 

[mr peabody]

Depressive symptoms rapidly reduced in largest ever psilocybin therapy trial*

by Emily Jarvie | PSYCHEDELIC SPOTLIGHT | 9 Nov 2021
​

“A single dose of psilocybin generated a rapid response that lasted up to 12 weeks,” explains principal investigator Dr. David J. Hellerstein, who was evaluating Compass Pathways' novel drug formulation COMP360.

A clinical trial carried out by mental health care company Compass Pathways has demonstrated the ability of psilocybin therapy to rapidly reduce depressive symptom severity for patients with treatment-resistant depression.

The trial, which we’ve been eagerly awaiting the results of, evaluated the efficacy of Compass Pathways’ psilocybin therapy drug, COMP360, in addressing treatment-resistant depression.

It was the largest psilocybin therapy trial ever conducted, involving 233 patients from 10 countries in North America and Europe. All patients discontinued their use of antidepressants before the study, and 94% of study participants had no prior experience with psilocybin.

The trial compared two active doses of COMP360, 25mg and 10mg, against a comparator 1mg dose. Each dose was administered in conjunction with the psychological support of trained therapists.

Patients who were administered 25mg showed a -6.6 difference on the Montgomery–Åsberg Depression Rating Scale (MADRS) at week three, compared to patients administered with just 1mg of COMP360. However, there was no statistically significant difference between the 10mg and 1mg doses at week three.

At least twice the number of patients in the 25mg group showed response and remission at week 3 and week 12, compared with the 1mg group. For patients in the 25mg group, the protocol-defined sustained response up to week 12 was 20.3%, compared to 10.1% for the 1mg group.

The trial’s principal investigator, Dr. David J. Hellerstein, a professor of clinical psychiatry at Columbia University Irving Medical Center, described the study as “ground-breaking.”

“A single dose of psilocybin generated a rapid response that lasted up to 12 weeks,” he explained. “Remission rates appear to be higher than seen in traditional medication studies. These findings suggest that COMP360 psilocybin therapy could play a major role in psychiatric care.”

However, during the trial, 179 of the study participants experienced treatment-emergent adverse events (TEAEs). 90% of these were mild to moderate in severity, most commonly headache, nausea, fatigue, and insomnia. A dozen patients experienced severe TEAEs, including suicidal behavior, intentional self-injury, and suicidal ideation. These events occurred more frequently in the 25mg group.

While the results of this trial were not as promising as many in the psychedelics sector were anticipating, they were positive overall and provide new hope for patients suffering from treatment-resistant depression.

Sadly, about 30% of people suffering from depression are treatment-resistant — a condition defined as the failure of a patient to respond to at least two anti-depressant treatments of different drug classes. More than 100 million people worldwide suffer from treatment-resistant depression, according to the World Health Organisation.

“We urgently need options for people who are not helped by existing therapies,” said Compass Pathways CEO and Co-Founder George Goldsmith. “With this compelling data, we will urgently progress our clinical development program and move closer to making this therapy accessible to patients in need, if approved.”

One goal of this trial was to determine the appropriate dose of COMP360 for a more extensive, Phase 3 research program, which Compass Pathways expects to begin in 2022.

*From the article here :
https://psychedelicspotlight.com/co...rial-ever-depressive-symptoms-rapidly-reduce/​

 

[mr peabody]

Coping with Antidepressants and Psychedelics

by Dr. Ben Malcolm | SPIRIT PHARMACIST | 11 Jan 2021

Both traditional antidepressants and psychedelics work primarily on serotonin neurotransmission and have been found helpful in treating or managing mental illnesses such as depression, although they appear to leverage different sets of coping mechanisms. This finding could have major implications into our understanding of when or how we would want to use them:

Traditional serotonin blocking antidepressants (e.g. SSRIs, SNRIs) are known to produce longer term neuroadaptive changes to the brain over weeks to months resulting in an enhanced tolerance to difficult conditions. This has been termed ‘passive coping’ because it allows the user to deal with their life more effectively. This explanation aligns well with what persons tell me about antidepressants: When the effects are helping, they mention “I stopped having emotional outbursts or daily crying spells” or “I just wasn’t bothered by the little things as much.” When the effects are unfavorable, they mention “I felt numbed out, like I couldn’t experience my full range of feelings.” The commonality between the stories is that emotional sensitivity was decreased. My analogy for this type of coping is ‘Weathering the Storm’.

Psychedelics can produce almost immediate shifts in mood and are being discovered as ‘psychoplastogens’ or agents that increase the ability for the brain to re-mold itself. Used therapeutically, these effects may result in the modulation of negative core beliefs or effective processing of emotional traumas that drives psychopathology. When things work well the effects can catalyze processes of positive self-transformation. Persons may mention a peak psychedelic experience feeling like “a factory reset for my brain” or that “I was rewired.” This tends to lead to processes of identity restructuring in the time afterwards. When things go sideways the user may feel that trauma was activated without resolution, leaving the user in a hypersensitive and challenging emotional state. The commonality is that emotional sensitivity was increased. My analogy for this type of coping is “Transformation and Change” (metamorphosis).

Keep in mind we are talking about serotonin; one of the most ancient, enigmatic, and complex of neurotransmitter systems. Any discussion we have at this stage is reductionist. For example, the paper this information was taken from focuses on comparing actions of drugs at 5HT1A vs 5HT2A receptors, yet there are a dozen other types of serotonin receptors cut out of the picture. Healthy to take with a pinch of salt ​

Use of psychedelics to catalyze transformation and change is not new. For example, traditional cultures have utilized psychedelics during rites of passage. Placed within our model of psychedelics as agents of adaptive change, use during times of life that naturally demand a high degree of adaptation may be advantageous. Another example of psychedelic use to aid in situational transition or change are those using psychedelics for existential anxiety associated with life-threatening illness.

Psychedelics are being explored for treatment of alcohol use disorder and quitting cigarettes, which ultimately involve habitual change and reduction of behaviors negative for health. Depression and anxiety are thought of as bio-psycho-social-spiritual illnesses due to the complex interaction between persons and their environment giving rise to symptoms of illness. It is often the situational circumstances (psychosocial stressors) of one’s life that precipitates or makes illness worse. Life presents challenging circumstances and most suffer to different degrees at certain junctures: The coping mechanisms employed during times of hardship range anywhere from healthful and promoting problem solving to toxic and promoting our demise.

The neuroscientific elucidation of psychedelics as agents that foster adaptive coping has the potential for application across a diverse variety of illnesses and life situations. Psychedelics are far from panaceas or magic bullets for ‘bad habits’ and do not automatically cause any shift in behavior, situation, or psychological perspective. There is much to be said for motivation and readiness for change that is prerequisite for sustained positive change. However, effects of psychedelics could increase the probability of positive change occurring or help clarify ambivalence that creates resistance to change. Supportive psychotherapy or psychedelic integration coaching can also increase the chances of sustained positive change.

Over the past 30 years we’ve been able to observe the effects of SSRI antidepressants in clinically depressed, anxious, or traumatized populations. Overall, we’ve observed modest benefits (small effect size) and increasing chronic use without reductions in persons experiencing the mental illnesses the medications are designed to treat. There are many times when increasing emotional sensitivity may not be desirable due to toxic life circumstances, however is it an optimal strategy to ‘weather the storm’ one’s entire life? This is not supposed to demonize antidepressants, argue positive transformations cannot be made with antidepressant use, or suggest they’re numbing agents that retard personal growth. On the contrary, my hope is that we learn to apply agents that enhance the right coping mechanisms at the right times to achieve the goals and fulfill the intentions of the user.

Dr. Ben Malcolm is a doctor of pharmacy, master of public health, and Board Certified Psychiatric Pharmacist. He provides consultation services, courses focused on psychedelic healing and pharmacology, as well as a monthly membership program.

Coping with Antidepressants and Psychedelics

spiritpharmacist.mykajabi.com

 

[mr peabody]

Psilocybin helped me overcome crippling depression*
​

by Travis Reilly | PSYCHEDELIC SPOTLIGHT | 11 Nov 2021

Jada Pinkett Smith and her son Jaden spoke candidly about their profound experiences with plant medicine on a new psychedelics-themed episode of the Smith family’s Facebook Watch series Red Table Talk.

Jada began Wednesday’s broadcast by telling viewers she’d struggled with “crippling depression” for 10 years before successfully overcoming it with mushroom therapy. “The thing about plant medicine is not only does it help you feel better but it helps you solve the problems of how you got there in the first place,” the 49-year-old producer and “Matrix Resurrections” star explained.

Jada isn’t the first member of her famous family to open up about mind-altering experiences with plant medicine, either. Just last month her movie star husband Will Smith came out of the psychedelic closet, revealing he’d found a “taste of freedom” after using ayahuasca. Their 23-year-old son Jaden hasn’t shied away from the psychedelic spotlight either. The actor and musician recently released a psychedelics-inspired mixtape.

Filling in for his sister Willow Smith on Wednesday’s Red Table Talk, Jaden revealed precisely what drew him toward plant medicine in the first place. “It started as pure curiosity, not believing that mushrooms could make you feel any sort of way—but then I had an experience,” he told his mother and grandmother, co-host Adrienne Banfield-Norris.

“For the first time, I had like an ego dissolution and that was the moment that really changed me,” he continued. “You get to a place where you’re blocked by something—whether it’s trauma, whether it’s your emotions, your ego, not being able to express yourself—and I feel like psychedelics are a way to tear down that wall and see what’s behind it.”

Jada Pinkett Smith and her son weren’t the only ones who shared their psychedelic experiences with viewers. Red Table Talk’s full panel of celebrity guests included investigative journalist Lisa Ling and her husband Dr. Paul Song, billionaire entrepreneur turned psychedelic enthusiast Bob Parsons, and psychedelics researcher and best-selling author Michael Pollan.

As an oncologist, Dr. Song was skeptical of psychedelic healing for years until problems at home convinced him to give a guided ayahuasca trip a try. “It was everything and more,” Dr. Song said, explaining plant medicine helped him come to terms with multi-generational family trauma and forge a deeper relationship with his wife and children.

“It’s been transformative, it really has,” Ling agreed.

Parsons’ story involved a different kind of healing. The GoDaddy and PXG Golf founder served with the Marine Corps during the Vietnam War and returned home with a severe case of post-traumatic stress disorder. Though his military training gave him the skills and confidence he needed to start up several multi-million-dollar companies, PTSD had a profoundly negative effect on his well-being. “I had a short temper. It for sure cost me two marriages,” he told Jada.

All that changed after he picked up a copy of Pollan’s “life-changing” book How to Change Your Mind, which explores the science of psychedelics, and it wasn’t long before Parsons went to work changing his own mind with psilocybin and ayahuasca. “I felt like being with people again. I felt like going out. My temper didn’t bother me again,” he said. “I was kind of like how I was before the war—I finally came home.”

Jada, Jaden, and their guests wrapped up the show with a discussion on the lack of diversity within the psychedelic community and the underrepresentation of Black people in clinical trials studying plant medicine’s therapeutic capabilities.

“The psychedelic world in the United States has been very white,” Pollan said, explaining African Americans generally use less psychedelics than their white counterparts. He had several theories why, too, including the fact plant medicine was still technically illegal and the country had a nasty history of enforcing drug laws differently among its Black citizens. But considering how encouraging the clinical trials for psilocybin had been thus far, Pollan speculated it wouldn’t be long until the FDA opened the door for therapists to start legally prescribing psychedelics to patients.

Jada Pinkett Smith liked her guest’s optimism.

“Plant medicine completely rehabilitated me from debilitating depression and it’s changed my life for the better,” she said. “So, I’m really hoping that we find a way that African Americans can have access to these plant medicines safely.”

*From the article here :

Jada Pinkett Smith Says Psilocybin Helped Her Overcome 'Crippling Depression'

Jada Pinkett Smith and her son, Jaden, host a "Red Table Talk" devoted to psychedelics with Michael Pollan and other guests.

psychedelicspotlight.com

 

[mr peabody]

​

New study suggests SSRI drugs can be used safely with psilocybin to treat depression

“If the results are confirmed in subsequent studies ... antidepressants may no longer need to be stopped for psilocybin treatment,” - Dr. Miri Halperin Wernli, MindMed Executive President

by Emily Jarvie | PSYCHEDELIC SPOTLIGHT | 30 Nov 2021

Biotechnology company MindMed has released new data showing how a selective serotonin reuptake inhibitor (SSRI) interacts with psilocybin in humans, providing preliminary evidence these drugs could be safely used together without impacting psilocybin’s effectiveness to tackle depression and anxiety.

SSRI drugs are the most commonly prescribed antidepressant that can relieve the symptoms of depression by increasing the level of serotonin — often referred to as the “feel-good hormone” because it is responsible for stabilizing our mood, feelings of wellbeing, and happiness — within a person’s brain.

Because psilocybin is being investigated as a treatment for depression and anxiety, it is vital to understand how this drug interacts with current antidepressant treatments. Before this study, it was unclear if antidepressant medicines would interact with psilocybin, with some case reports indicating that antidepressants may reduce a person’s response to psychedelics.

The MindMed-sponsored study, carried out by the University Hospital Basel Liechti Lab, showed that pre-treatment with the SSRI escitalopram had no relevant impact on the positive mood effects of psilocybin. However, it significantly reduced negative effects such as anxiety and adverse cardiovascular reactions when compared with a placebo pre-treatment in healthy human participants.

For the study, participants either received 10mg of escitalopram daily for seven days followed by 20mg daily for the next seven days, including the day of psilocybin administration, or 14 days of placebo pre-treatment before psilocybin administration.

The researchers found that pre-treatment with escitalopram did not alter the pharmacokinetics of psilocin — the active compound that the prodrug psilocybin is converted into in humans by the process of dephosphorylation. The half-life of psychoactive psilocin was 1.8 hours, with a range of 1.1 to 2.2 hours, which was consistent with the short duration of action of psilocybin.

It also did not alter QTc intervals (a measure of hearth rhythms) or circulating brain-derived neurotrophic factor (BNDF) levels before or after the administration of psilocybin.

“Two key questions arise around the use of psilocybin in patients undergoing antidepressant treatment,” explained the study’s Principal Investigator, Dr. Matthias Liechti.

“First, for safety reasons, should a patient stop using antidepressants before receiving psilocybin? Second, if there’s no safety risk, will the antidepressant reduce the patient’s response to psilocybin?”

“These results indicate that psilocybin may be dosed during escitalopram treatment without apparent impact on the effect of psilocybin. Thus, the study answers the first question and provides a positive indication for the second.”

The results of this study highlight important areas for future research, with the authors suggesting studies with a longer antidepressant pre-treatment time and patients with psychiatric disorders to define interactions between antidepressants and psilocybin further.

“If the results are confirmed in subsequent studies, with other substances and in patients rather than healthy individuals, antidepressants may no longer need to be stopped for psilocybin treatment,” added MindMed’s Executive President Dr. Miri Halperin Wernli. As the researchers noted, this would eliminate the risk of adverse effects due to escitalopram treatment interruption to participate in a psilocybin treatment, for example, in a clinical trial or for compassionate use.

*From the article here :

Study Suggests SSRI Drugs Can Be Used Safely with Psilocybin | Psychedelic Spotlight

If results hold up in subsequent studies, SSRI drugs may no longer need to be stopped for patients to undergo psilocybin treatment.

psychedelicspotlight.com

 

[mr peabody]

Trial finds psilocybin effective in treating serious depression*

by Olivia Goldhill | STAT | 9 Nov 2021

Eagerly awaited results of the largest-ever study of psilocybin were announced Tuesday, with Compass Pathways revealing the psychedelic drug was highly efficacious as a therapy for treatment-resistant depression.

The Phase 2b study is the largest randomized, controlled, double-blind trial of psilocybin, the psychedelic compound in magic mushrooms. The company said it found that patients who were given the highest dose, 25 milligrams, had a significant decrease in depressive symptoms compared to those given 1 milligram, which is such a low dose it functions as a placebo.

Overall, 29.1% of patients in the highest-dose group were in remission three weeks after treatment, compared to 7.6% of those in the control group, and more than a quarter of the patients in the 25-milligram arm were still in remission three months after treatment.

Those who received the highest dose also experienced an average reduction on a measure of clinical depression (the Montgomery-Asberg Depression Rating Scale) that was 6.6 points greater than those who took 1 milligram. Other patients were given a 10-milligram dose, but there was not a statistically significant impact for those patients compared with the 1-milligram arm.

“Everyone agrees such a result hasn’t been seen before in depression research, so we’re incredibly happy with that result,” said Lars Christian Wilde, co-founder and president of Compass.

Boris Heifets, a neuroscience researcher at Stanford who studies psychedelics and was not part of the study, agreed the results are “super promising.” "The effectiveness of psilocybin at three weeks, according to Compass’ study, is roughly comparable to the effects of ketamine at one day, according to a smaller 2013 study," he added, which suggests the benefits of psilocybin hold up well over time. “We’re still missing a lot of the detailed data,” he added, but the summary results are “pretty good news.”

The study, which enrolled 233 patients at multiple sites across Europe and North America, is the most rigorous trial on psilocybin for treatment-resistant depression and adds considerable weight to earlier, smaller studies of the drug that were also promising. The U.S. Food and Drug Administration has granted Compass Pathways’ treatment breakthrough therapy designation, meaning the drug approval process will be accelerated if studies continue to show positive results. Compass is working toward starting a Phase 3 trial next year; current results suggest it’ll likely use a 25-milligram dose, but Wilde said that decision will be made following conversations with regulators.

The results released by the company, which have not been published in a medical journal or peer-reviewed, included side effects data showing a small number of serious adverse events. Overall, 12 patients reported treatment-emergent serious adverse events, five of whom were in the 25-milligram group and six in the 10-milligram group; these included suicidal behavior and self-injury. Just one patient in the 1-milligram group experienced a serious adverse event.

“The suicidal behaviors were reported at least one month after the administration of treatment and they occurred in patients who were essentially non-responding,” Guy Goodwin, Compass’ chief medical officer, said in an investor call Tuesday morning. "In at least one case, though, suicidal ideation was reported early on in treatment," he added.

"The numbers are small enough for the difference between treatment arms not to be statistically significant," said Wilde, noting that suicidal behaviors and ideation are common among depressed patients. “We’re dealing with a severe patient population, both in terms of patient severity and duration of their depressive episode,” he said. “Unfortunately, those events have to be expected.” There were three suicides in studies of esketamine, the only psychedelic currently approved for treatment-resistant depression, he pointed out.

"Researchers in previous studies have reported a “disappointment reaction,” whereby patients’ symptoms worsen because the novel treatment doesn’t immediately cure their depression. The difference between the treatment arms is unexpected," said Heifets, as patients tend to get more depressed if they’re assigned to placebo and don’t get effective treatment: “If anything, I’d expect it to go the other way.” But, he added, suicidal behaviors are common in research on depressed patients. “That means it’s not attributable to psilocybin having a suicidal side effect,” he said.

Goodwin said the researchers plan to study the data in more detail, including analyzing responses to a questionnaire all patients took for suicidal assessment, to better understand the connection.

*From the article here :

Psilocybin trial finds psychedelic is effective in treating depression - STAT

Overall, 29.1% of patients in the highest-dose group were in remission three weeks after treatment, compared to 7.6% in the control group.

www.statnews.com

 

[mr peabody]

​

5-MeO-DMT formula yields positive TRD trial results*

by David E. Carpenter | Benzinga | 6 Dec 2021

Clinical-stage biopharmaceutical company GH Research PLC announced positive results from recent clinical trials of its leading 5-MeO-DMT formula, a therapy candidate for patients suffering from treatment-resistant depression (TRD).

The Ireland-based company, which this year announced a capital raise of $315 million, is focused exclusively on research around the psychoactive molecule 5-MeO-DMT to treat depression, a condition that affects many millions of people around the world. Currently, an estimated 50 percent of patients receiving therapy for TRD do not respond to approved depression medications.

The lack of effective treatments for TRD has created a market for companies like GH Research seeking to develop such therapies, potentially changing the way TRD is treated today. So far, GH Research is on track to validate claims that their proprietary GH001 5-MeO-DMT formula is safe and could provide relief from TRD with no serious adverse events for patients.

Completing two Phase 1 healthy-volunteer clinical trials and a Phase 1/2 clinical trial in patients with TRD, studies have so far revealed that 87.5% of patients were brought into an ultra-rapid remission after an individualized single-day dosing regimen using GH Research’s inhalable 5-MeO-DMT product.

Fast action the key: Part of what makes the substance valuable for clinicians treating depression is the drug’s potency and fast-acting nature, with onset occurring within seconds and treatments lasting on average a relatively rapid 15 to 20 minutes. Shorter duration psychedelic treatments will likely scale better than other psychedelic treatments, such as therapies using psilocybin or MDMA, which can require five to eight hours from clinicians involved in administering and monitoring patients.
​

Biopharmaceutical companies are keenly aware of creating therapies that require less time and fewer clinician hours in the hopes of health insurance providers covering treatments, as is the case with ketamine treatments.

Another key action of 5-MeO-DMT is its ability to produce ego loss or “ego death” during an experience using the drug, which can produce valuable insights that change one’s overall perception of life and its difficulties.

Making news headlines over the last month was heavyweight fighter Mike Tyson’s endorsement of the substance as a positive catalyst that transformed his life.

“I ‘died’ during my first trip,” Tyson said. “In my trips, I’ve seen that death is beautiful. Life and death both have to be beautiful, but death has a bad rep.”

Found naturally in small quantities in some plants, 5-MeO-DMT is most notably found in higher concentrations in the dried venom of the Bufo alvarius toad, also known as the Sonoran Desert toad. The amphibian’s defense secretions have been the source of mounting exploration in the psychedelic underground since the 1980s.
​

The substance has made its way over the past decade into labs like GH Research, with the mounting use of synthetic forms of 5-MeO-DMT employed to study potential therapies for TRD.

One important study in 2019, which garnered interest in the drug and its use for depression, showed that participants who experienced high levels of “ego dissolution or oceanic boundlessness during their session displayed higher ratings of satisfaction with life and lower ratings of depression and stress.”

GH Research has plans to request an initial investigational new drug (IND) meeting with the FDA in the first quarter of 2022, reported Green Market Report.

An IND approval from the FDA would provide the drugmaker authority to proceed to the next stage of trials if the experimental drugs are showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

GH Research also stated that it has recently initiated development in two undisclosed psychiatric disorders which are expected to be announced in the first quarter of 2022.​

*From the article here :
https://markets.businessinsider.com...for-treatment-resistant-depression-1031027141
​

 

[mr peabody]

Powerful psychedelic improves depression in one hour*

Psychedelic found to treat mental health conditions more efficiently than psilocybin, study.

by Molly Hanson | BIG THINK

• A survey study found that around 80 percent of people using the psychedelic 5-MeO-DMT in a ceremonial setting said that their depression or anxiety improved following its use.​
• The "mystical" experience of drug trip might allow people to gain unique insight into themselves or their relationships and make positive life changes.​
• While the substance is found in the poison of the Sonoran Desert Toad, researchers say there is no reason to disturb the toad because the synthetic version of 5-MeO-DMT is identical in its effect.​

A new, powerful — yet still relatively rare — hallucinogen called 5-MeO-DMT has made its way into United States psychedelic circles, and research is backing its use as an effective treatment for certain mental health conditions.

Said to be up to six-times more intense than its sensationalized cousin DMT, researchers have found strong evidence to suggest that 5-MeO-DMT could be used to treat anxiety, depression, and addiction more efficiently than psilocybin.​

What is 5-MeO-DMT?

5-MeO-DMT, is an extremely potent natural psychedelic found in certain plants and the poisonous secretions of the Sonoran Desert Toad, also known as the Colorado River Toad. It can also be made synthetically in a lab.

Typically, the experience a person has after ingesting 5-MeO-DMT, a schedule 1 classified substance, is described as feeling unified with the universe or some holy, transcendent “other.” The perception of bright colors and recursive patterns are often associated with the experience. It can also lead to extreme nausea and confusion days after ingesting it.

Assistant Professor at Ohio State University Alan Davis, who is also affiliated with the Department of Psychiatry and Behavioral Sciences at John Hopkins University, has conducted two large-scale survey studies examining the use of 5-MeO-DMT in the general population and in a specific ceremonial group in the United States.

Despite reports dubbing it the “hottest new psychedelic” among trend setters in the United States, Davis’s research has found that the drug is still rare, and most people are using it for psycho-spiritual endeavors rather than for recreation. Typically, he says, it is used in a ritualistic setting with a specific process similar to what might be done during an ayahuasca ritual.

And, he emphasizes, it definitely isn’t a party drug.

“This is a very potent and powerful psychedelic substance that usually has an onset within seconds and a person is completely incapacitated,” he says. “They are in a whole different realm of consciousness for 20 to 60 minutes.”​

Research in treating anxiety and depression

In a survey study of 362 adults, Davis found that when administered in a ceremonial group setting with a knowledgeable facilitator, approximately 80 percent of people said that their depression or anxiety is improved following the use of 5-MeO-DMT.

According to Davis, this is likely because of the type of “mystical” experience one has on the drug trip, which allows the person to gain new, novel insight into themselves or their relationships through a shift in consciousness.

“This information, these experiences, seem to be really powerful and profound and they seem to help people to change, and to make different choices in their life,” says Davis.

Interestingly, this fits in with research on other psychedelic substances such as psilocybin, which has also been found to have significant anti-depression and anti-anxiety effects. One of the major downsides to the potential use of psilocybin in a clinical setting is that the psychedelic experience lasts four to six hours. Tacking on an extra hour before to get ready and after to ensure the patient is ready to be discharged, psilocybin would mean a whole day of treatment. That will add up to a very expensive session if it is eventually approved for public use, according to Davis.

Enter 5-Meo-DMT.

“One of the interesting things about 5-Meo-DMT is that the duration of effect is anywhere from 20 to 60 minutes,” says Davis. “You can start to imagine a world where if this was a medication, you could actually have someone there for more of a standard psychotherapy time frame and have an entire psychedelic healing experience.”

Because this treatment could more easily be scaled into our current mental health care, it would likely be more accessible to people who might benefit from the treatment. Currently, Davis is working with a larger team on creating a clinical trial with the aim to eventually look at the administration of the drug in a laboratory setting.

Although Davis’s team has heard of potential risks involved with use of the drug, in part because of instances of it being mis-administered, he says that the data indicates that in the right setting where facilitators pay proper attention to people’s well-being, users are having mostly positive experiences.

As far as researchers know, the only animal on Earth that produces the chemical compound is the Sonoran Desert Toad, although it is also found in some plant species.

But the mystical psychedelic association with the toad has facilitated an ecologically harmful market for the amphibian’s poisonous secretions. This has led researchers to strongly condemn the practice of harvesting the toads for the compound.

According to local Tucson naturalist Robert Villa, the toad produces is milky white poison as a defense mechanism, so there is no humane way to obtain it. People in the Sonoran Desert region, where the toad is native, have noticed a decline in the amphibians’ numbers likely due to the psychedelic community’s demand for 5-MeO-DMT.​

“Traumatizing an animal (or plant) for personal benefit is fraught with ethical dilemmas,” Villa wrote in an email.

Faced with other threats to its habitat, the psychedelic blackmarket is one more problem the Sonoran Desert Toad doesn’t need. Davis stresses that there is no need to disturb the toads or their environments at all.

“What we’ve been able to show is that the synthetic version is no different in terms of the intensity or the positive effects of taking it compared to the toad,” says Davis. In fact, he found that most of the people he surveyed in his study were using the synthetic version of the drug.​

*From the article here :

Meet 5-MeO-DMT, the 'powerful' psychedelic that improves depression in one hour

A newly studied hallucinogenic substance has shown signs of treating mental health conditions more efficiently than psilocybin.

bigthink.com