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The Psychedelic Revolution in Psychiatry

Cell Press | Science Daily | 2 Apr 2020

Before they were banned, psychedelic drugs like LSD and psilocybin showed promise for treating some psychiatric disorders.

In a commentary publishing April 2 in the journal Cell, researchers say it's time for regulators, scientists, and the public to "revisit drugs that were once used, but fell out of use because of political machinations - especially the war on drugs."

Brain imaging over the past 20 years has taught scientists a lot about how these drugs act on different areas of the brain, says David Nutt, a professor and neuropharmacologist at Imperial College London. "There's mechanistic evidence in humans of how these drugs affect the brain," he says. "By back-translating from humans to rodent models, we can see how these drugs produce the powerful neuroplastic changes that explain the long-term alterations we see in humans."

Nutt is a prominent proponent of conducting controlled trials to examine the potential benefits of psychedelics. He is also chair of the scientific advisory board for COMPASS Pathways, a for-profit company that is leading clinical research to test the safety and efficacy of psilocybin-assisted therapy for treatment-resistant depression. The treatment has been granted breakthrough therapy designation from the US Food and Drug Administration. The group also plans to launch a similar study for obsessive-compulsive disorder.

In the Cell commentary, Nutt and his colleagues write about the "psychedelic revolution in psychiatry." They explore specific questions in research, including what is known about the receptors in the brain affected by these drugs and how stimulating them might alter mental health. They also address what's been learned so far about so-called microdosing, the value of the psychedelic "trip," and what researchers know about why the effects of these trips are so long-lasting.

Brain imaging has shown that the activity of psychedelic drugs is mediated through a receptor in brain cells called 5-HT2A. "There is a high density of these receptors in the thinking parts of the brain," Nutt explains.

The key part of the brain that appears to be disrupted by the use of psychedelics is the default mode network. This area is active during thought processes like daydreaming, recalling memories, and thinking about the future -- when the mind is wandering, essentially. It's also an area that is overactive in people with disorders like depression and anxiety. Psychedelics appear to have long-term effects on the brain by activating 5-HT2A receptors in this part of the brain. More research is needed to understand why these effects last so long, both from a psychological perspective and in terms of altered brain functioning and anatomy.

The authors note the challenges in obtaining materials and funding for this type of research. "Before LSD was banned, the US NIH funded over 130 studies exploring its clinical utility," they write. "Since the ban, it has funded none."

Nutt highlights the early potential of psychedelic drugs for treating alcoholism, which the World Health Organization estimates to be the cause of about one in 20 deaths worldwide every year. "If we changed the regulations, we would have an explosion in this kind of research," Nutt says. "An enormous opportunity has been lost, and we want to resurrect it. It's an outrageous insult to humanity that these drugs were abandoned for research just to stop people from having fun with them. The sooner we get these drugs into proper clinical evaluation, the sooner we will know how best to use them and be able to save lives."

 
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Psychedelic drugs—a new era in psychiatry?

by David Nutt David Nutt, DM, FRCP, FRCPsych, FMedSc | 2019

This article covers the renaissance of classical psychedelic drugs such as psilocybin, LSD and MDMA in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards.

INTRODUCTION

Psychedelics of plant extraction such as mescaline and psilocybin have been used for millennia in cultures all across the globe, but Western science was not introduced to them until 1897, when Arthur Heffter isolated mescaline. The real breakthrough came with the discovery of LSD in 1943 by Albert Hofmann at Sandoz as a synthetic variant of ergot alkaloids. Following his famous descriptions of his first exposure he persuaded Sandoz to make LSD available to researchers across the world under the trade name Delysid, and Sandoz made it freely available to those interested in researching its properties. Hofmann also identified the active component of “magic” mushrooms as psilocybin. This was also made available by Sandoz as Indocybin. It should be noted that psilocybin is in effect a prodrug, and is converted into the active ingredient psilocin in the body.

Research with LSD, in particular, flourished and the US government, in the form of the National Institutes of Health, is reputed to have funded over 130 grants for its study (but none since the 1967 ban). Before the ban hundreds of papers were published on LSD (and to a lesser extent psilocybin). Because LSD, psilocybin, and other hallucinogens mimicked some of the symptoms of acute psychosis, particularly ego-dissolution, thought disorder, and misperceptions, it suggested the possibility that an endogenous psychotogen might cause schizophrenia. It also seemed to allow access to repressed memories and emotions and so “unblock” people failing in psychotherapy. LSD appeared very safe in relation to other psychotropic agents used at that time, especially the barbiturates which were very toxic in overdose, whereas the psychedelics rarely had lasting medical effects, even after overdose. Indeed a long-term follow-up analysis of the impact of the tens of thousands of LSD administrations given in the 1950s and 1960s reported no increased level of psychiatric problems. One more negative note is the fact that some saw LSD as a potential weapon in warfare rather than as a therapeutic advance. This was seen in both the West and in communist countries who developed their own drugs when Sandoz would not supply them.

One area of particular interest was in the treatment of alcoholism. This derived from the personal psychedelic experience of Bill Wilson which led to his becoming alcohol-free, and so also led to the founding of Alcoholics Anonymous. Wilson’s own experience made him convinced of the value of LSD to give alcoholics insight into how they might overcome their drinking addiction. He encouraged the use of LSD in the treatment of alcoholism, and six trials were conducted before the drug was banned. These data were recently subjected to a modern meta-analysis and LSD therapy was found to be at least as efficacious a treatment as anything we currently have today. Of interest to psychotherapists, Wilson also believed that LSD could give unique and immediate insights into the unconscious mind. He wrote to Jung encouraging him to explore this potential but Jung, who was approaching death at the time, didn’t seem especially enthusiastic and apparently replied to the effect that dreams were good enough!

In 1967, LSD was classified under Schedule I of the 1967 United Nations convention on drugs, and most other psychedelics, particularly psilocybin and mescaline, were also included even though there was very little evidence of harm. Schedule 1 drugs are defined as having no accepted medical use AND significant potential for harm and dependence, so despite this schedule clearly being quite unscientific for these drugs they have remained there ever since. This scheduling effectively censored research on psychedelics for over 40 years and only in the past decade have attempts been made to reverse this.

Other drugs with therapeutic potential: MDMA and Ketamine

MDMA was quite widely used as a tool for psychotherapeutic purposes, especially couple counseling, when it was known as empathy. However, once its name was changed to ecstasy and it began to be used in the rave recreational scene it was banned and therapeutic use largely stopped. Since that time the charity MAPS (the Multidisciplinary Association for Psychedelic Studies) led by Rick Doblin has campaigned to have it restored as a medicine.

Though MDMA isn’t a psychedelic in the true sense of the word, it does have profound effects that allow people to gain insight into their psychiatric problems, and has proved especially helpful in the treatment of post-traumatic stress disorder (PTSD). Several studies run by the Mithoefers have demonstrated that a couple of sessions of exposure- therapy under MDMA (usually 125 mg + a 62.5-mg top-up after 2 hours) can have powerful therapeutic effects. The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have now both given their approval for multicenter studies in the USA and Europe, and if these are positive then it seems likely that MDMA will also become an approved medicine sometime in the 2020s.

We are currently conducting BIMA—the Bristol University MDMA for Alcoholism trial. This is an open trial of MDMA (two sessions given as in the PTSD trials) for patients with alcoholism. The rationale for this is that many such patients are drinking alcohol excessively to deaden painful memories of trauma. If MDMA therapy could help them overcome these memories then they might be able to stop or reduce their drinking.

Ketamine is an old established dissociative anesthetic that has in recent years been used in lower doses as an analgesic. Like psychedelics and MDMA, it is also used recreation-ally to produce altered states of consciousness which are psychedelic-like. When John Krystal at Yale started to use ketamine as an experimental medicine model of psychosis, he noted that people often experienced an improvement in mood once they had recovered from the trip. This led him and a colleague, Carlos Zarate, to conduct a trial in patients with resistant depression with good outcomes. A single IV dose of ketamine could produce an improvement in mood lasting up to 4 days. Since then there have been many related studies conducted with ketamine. Also its active enantiomer, s-ketamine (given intranasally) has been developed commercially and may well be licensed in the near future. All forms of ketamine have to be given twice weekly to maintain their antidepressant effects. These two different forms of ketamine are both thought to act as glutamate antagonists of the NMDA receptor system. This action thought to lead to a disruption of the abnormal brain circuits that underpin depression.

The pharmacology of psychedelics

The key target for the psychedelic drugs is the serotonin 5-HT2A receptor where they are agonists, ie, they stimulate the receptor. Most psychedelic drugs also have actions at other serotonin receptors such as the 5-HT1A and 5-HT2B receptors where again they have agonist or partial agonist activity. However these probably do not contribute to the psychedelic effects; we know that 5-HT2A receptor agonism is what produces the psychedelic effects because Franz Vollenwieder’s group has shown convincingly that these are fully blocked by the selective 5-HT2A antagonist ketanserin.


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The modern-day resurgence of psychedelics in psychiatry

The process of resuming clinical research with psychedelics came from two parallel directions. One was the development of neuroimaging and psychopharmacological studies conducted in healthy volunteers and the second from some small exploratory clinical studies.

Since the 1990s several groups have begun to apply modern research methods to psychedelics with Strassman et al in the United States using DMT, and Vollenweider et al in Switzerland using psilocybin. My own group started in the 2000s with psilocybin and conducted the first systematic fMRI studies with this drug. The results were unexpected and surprising because we found that the main effect of psilocybin was to decrease brain blood flow and blood oxygen level-dependent (BOLD) activity predominantly in the default mode network (DMN) but including the subgenual cingulate cortex.

Since several neuroimaging studies have found overactivity in this brain region in depression and many different treatments of depression have been found to suppress activity here, this finding seemed of interest for depression. Also it was relatively common for our volunteers to report improved mood and well-being after their psilocybin administration (even when the drug was given in a scanner). For these reasons we wondered if the same decreased activity in the subgenual cingulate cortex might occur after psilocybin in depressed patients and this might then elevate mood. It was this translational medicine insight, supported by earlier clinical data, that led to our MRC-funded trial in resistant depression described below.

As well as imaging studies there was also a hugely influential psychopharmacological experiment conducted by Roland Griffiths and his team at John Hopkins university in Baltimore. They gave healthy non-psychiatrically ill volunteers a single 25-mg oral dose of psilocybin in a psychotherapeutic setting and followed them up for many years. A control group treated in the same way received a dose of the stimulant methylphenidate. In contrast to the methylphenidate group who had little in the way of long-term benefits, most of the psilocybin participants found the experience rewarding and insightful and many said it was one of the most significant experiences of their lives, ie, being in the top five of their life-time positive experiences. Moreover this positive outcome lasted for very many years. This was the first systematic controlled study of the use of a psychedelic to give insights and produce well-being in normal volunteers, and served as the basis on which subsequent patient studies were conducted. For example in our studies we use the same 25-mg oral dose and setting as the Griffiths work.

The first modern clinical trial of a psychedelic was by Francisco Moreno and colleagues, at the University of Arizona in 2006. Nine subjects with treatment-resistant OCD were given up to three different doses of psilocybin in an open-label design. Significant reductions in OCD symptoms were observed but no clear dose effect was seen. Importantly there were no serious adverse events. The trial was reputedly stopped because of the extreme costs involved in working with a controlled drug! This is a common problem, as discussed later.

The Griffiths team at Johns Hopkins have subsequently conducted several clinical trials. The first was an open study in people trying to quit tobacco smoking. Fifteen otherwise psychiatrically healthy smokers in a structured 15-week smoking cessation treatment program were given 25 mg psilocybin three times. Biological markers of smoking, eg, urinary cotinine level as well as smoking craving and urges, were assessed up to 6 months. Remarkably 12 of the 15 subjects became and remained smoking-free at 6 months—an extremely significant outcome. The Hopkins team have also conducted one of the two most recent studies on psilocybin for end-of-life depression and anxiety, which are discussed as a group below.

The other addiction study with psilocybin was conducted by Michael Bogenschutz and colleagues at the University of New Mexico. They gave two psilocybin sessions to 10 alcohol-dependent patients in addition to standard therapy. The primary outcome was the percentage of heavy drinking days, and very significant reductions in this metric were found with no concerning adverse effects of the psilocybin.

One pilot study using psilocybin in major depressive disorder has also been published in the modern literature. In this, our own open-label pilot study, we gave two doses of psilocybin (a 10-mg “test” dose and a 25-mg therapeutic dose) 1 week apart with psychological support before and after the experience to 20 patients with treatment-resistant depression who were moderately to severely depressed. In reality the participants were mostly multiply treatment-resistant, and the illness was very long-standing. As serotonergic antidepressants and 5-HT2A receptor antagonist antipsychotics block the effects of psilocybin, patients were withdrawn from these before getting the psilocybin treatment. The primary outcome measure was the mean change in the participant-rated quick inventory of depressive symptoms (QIDS-SR) rating scale with follow-up was for 6 months, Highly significant improvements in depression ratings were seen at all time points with the maximal significance of effect seen at 5 weeks. The trial established feasibility and evidence of safety, but efficacy interpretations are limited by the open-label design.

All the above clinical studies suffer from the major problem of being open-label designs. This is acceptable for early stage research but a challenge for effectively proving the therapeutic efficacy of psychedelics. However, in the past couple of years a few controlled clinical trials have now been carried out. Four separate controlled studies have been published on the use of psychedelics in end-of-life anxiety and depression associated with life-threatening illness. Gasser et al used LSD either a low (20 ug) or a high (200 ug) dose whereas the other three studies all used psilocybin.

Charles Grob and colleagues in California gave 12 subjects (11 women) a moderate (0.2 mg/kg) dose of psilocybin and an active placebo (niacin 250 mg) in a double-blind design in which subjects acted as their own controls. All subjects had advanced cancer diagnoses and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-defined acute stress or anxiety disorders as a result of their cancer diagnosis. The treatment was well tolerated and all 12 completed the 3-month follow up. Non-significant trends towards improvements in mood were observed, perhaps because of the small numbers and relatively low dose of psilocybin used.

Two larger, double-blind, randomized, placebo-controlled, crossover trials investigating the efficacy of psilocybin in the treatment of anxiety and depression in patients with life-threatening cancer diagnoses have since been published simultaneously from two separate groups in the USA. Roland Griffiths and his John Hopkins team treated 51 patients with anxiety and depressive symptoms occasioned by life-threatening cancer diagnosis. Placebo was a very low (ineffective) dose of psilocybin (1 mg or 3 mg/70 kg) compared with the much higher active treatment dose (22 mg or 30 mg/70 kg). Administration was counterbalanced with 5 weeks between sessions and 6-month follow up. The Hamilton Depression and Anxiety scales were the primary outcome measures, and showed superiority for the high dose versus the low dose at 5 weeks. The crossover high-dose group then experienced a significant improvement also. Significant associations between mystical-type experiences and enduring positive changes were also observed, as in previous research of this group.

In a similarly designed study Stephen Ross and colleagues at NYU gave 29 patients a single dose of 0.3 mg/kg psilocybin or 250 mg niacin as active placebo with crossover at 7 weeks. The treatment was delivered safely, with no reports of serious adverse events. The group receiving psilocybin showed clinical benefits as measured by both clinician and participant rated scales that lasted for the 7 weeks prior to crossover and were also sustained approximately 8 months after dosing. The group that received niacin instead showed transient reductions that were not sustained at 7 weeks. After they crossed over to psilocybin, they also showed immediate and sustained reductions in anxiety and depression scores that were sustained at follow-up at 6 months.

As a result of these positive studies the EMA and the FDA have both given their approval for a multicenter multi-country trial of psilocybin run by the UK-based pharmaceutical company called COMPASS Pathways. This will involve randomization to one of three doses: 1, 10, and 25 mg given once only in patients who have failed two prior antidepressant treatments in their current episode. The study started at the beginning of 2019 and should report in 2020/21. If positive then both regulators have indicated a willingness to approve psilocybin as a medicine. In the USA the company USONA is also in the process of developing psilocybin as a medicine.

It is also important to record that other studies with different psychedelics have been conducted. I have already mentioned the LSD trial by Gasser in Switzerland, and this has led to this drug being made available for compassionate use in named patients by a few psychiatrists in that country.

A number of countries in South and Latin America allow the use of ayahuasca drink for religious and therapeutic purposes. This drink contains a mixture of plant products, one of which contains the psychedelic dimethyl tryptamine (DMT) and the other a monoamine oxidase inhibitor, harmaline. The harmaline blocks the activity of mono-amine oxidase inhibitors in gut and liver, and so allows enough of the DMT in the drink to enter the brain and so have its psychedelic effects. Human neuroscience studies of ayahuasca have shown it to have similar effects to psilocybin and LSD, and several clinical trials have taken place in depressed patients. For example Osorio gave ayahuasca to 6 medication- and ayahuasca-naive participants and found significant reductions in depression, as shown by the Hamilton Depression Rating Scale and Mongomery-Åsberg Depression Rating Scale up to 2 weeks after treatment. Sanches et al conducted another open-label study in 17 patients and again, highly significant reductions in depres-sive symptoms were observed up to the 3-week end point. A double-blind study has since been conducted, also with positive outcomes.

Current challenges and future prospects

The resurrection of psilocybin research is still in its infancy. There have been very few double-blinded studies, and total patient numbers are very low, less than 200 in all. This means we must be very cautious in making claims about the value of psychedelic therapy in psychiatry. Much more needs to be done, and the key question is how best to do this.

In the following sections I highlight what I think are the key issues that the field needs to take into consideration if this exciting yet still only promising new research area is to be properly assessed.

The first point to be made clear is that treatment with psychedelics and MDMA is a complex procedure that requires a great deal of therapists’ time and involvement. It had been suggested that this is a new era of psychiatric treatment—drug-assisted psychotherapy (or even psycho-therapy-assisted drug treatment). Patients have to be properly prepared for the powerful impact of the psychedelic session, and this involves at least one dedicated session with a trained therapist (often called a guide) before the drug session. In this prep session the patient is educated about the rationale, purpose, and procedure of the treatment session.

The drug session itself is given in a room with soft ambient lighting and a comforting soundtrack (which may contribute to the therapeutic value as well). There are generally two therapists present in the room (ideally one male and one female) who are there to provide reassurance, medical cover, and care. They only talk with the patient if the patient wants them to, which they generally do not. It is important to note that there is no expectation of conversation during the “trip” and no direction by either therapist of the patient’s speech or thought. It is the next day in the “integration” session that the content of the trip is discussed and interpreted and psychotherapeutic benefits derived.

Some critics of the procedure have argued that such intensive therapist input may constitute the therapeutic process, rather than the drug itself. Others have questioned whether the drug alone without therapy might work just as well. These are fair scientific points, but the reality of the power of a trip is such that we believe to allow one without medical and therapist cover would be unethical. The argument that it is all a powerful psychotherapeutic placebo is not sustainable because of the Griffiths and Ross double-blind studies where placebo + intense psychotherapy did not work as well as psychotherapy plus the active drug.

The question of safety is important. Although the banning of psychedelics and MDMA was made on the basis of largely fictitious claims of harm, there is no doubt that the psychedelics in particular are powerful mind-altering drugs, that can leave deep negative as well as positive memories. A more recent analysis of comparative experiences from, and adverse effects of, psilocybin has been produced.

There is also the risk of precipitating or worsening psychosis. For the latter reason we exclude anyone with a history of psychosis in themselves or in first-degree family members. So far we have also excluded patients with bipolar depression in case mania might be precipitated. With these precautions we have found adverse effects to be rare, and no-one has asked to stop the treatment. However, unlike with recreational users we found that very few of the depressed patients enjoyed the experience. They found confronting their depressive thoughts and memories quite challenging, but afterwards almost all felt the experience had been worth-while. However, we were prepared for anyone needing to be rescued from a severe bad trip by having a parenteral form of a benzodiazepine ready as escape medication. This, we have found, worked in an earlier study with LSD where one subject wanted relief. An extra safety measure held in readiness is the 5-HT2A receptor-blocking antipsychotic drug, olanzapine.

One common clinical challenge is the fact that so many patients are already on antidepressant and other drugs that block the effects of psychedelics. 5-HT2A receptor-blocking antipsychotic drugs such as quetiapine and olanzapine completely block the access of the psilocybin to the 5-HT2A receptor, so it is unable to work. Also, the selective serotonin reuptake inhibitors (SSRIs) desensitize these receptors and so reduce the psychedelic’s effects.40 We found that stopping these is often necessary, but of course is associated with the risk of worsening the underlying depression and also inducing withdrawal or discontinuation reactions, so this needs to be done slowly and carefully.

The legal status of this treatment is also a challenge, as all psychedelics and MDMA are listed in the UN Conven-tions as Schedule 1 drugs. Despite the growing evidence of efficacy and safety they are still subject to intense legal controls. This means that getting supplies is extremely difficult and time-consuming, and very expensive. I calculated that the cost of each administration of psilocybin in our first psilocybin depression study cost about £1500 and took 2 years to procure. Until these regulations are reformed, this research will thus continue to be very limited and the therapeutic utility of these remarkable drugs will take an unnecessarily long time to be properly evaluated.

Finally, how do these drugs work? The current thinking with psychedelics and depression is that they disrupt the dysregulated brain circuits that underpin depression. In the introduction I already mentioned the switching down of activity in the subgenual cingulate cortex by psilocybin, in common with other treatments for depression. Another interesting and related idea is that of psilocybin switching off the default mode network (DMN). For example, Berman and colleagues have demonstrated that in depressed people a much greater amount of brain is active in the DMN condition than in healthy controls. This overengagement of the DMN appears to be a cause—or maybe a manifestation—of the intense self-deprecatory rumination that depressed patients experience. Psychedelics significantly disrupt ongoing DMN activity. So, for the duration of the trip the depressive processes are also disrupted. This in itself may give the patients a view of a depression-free world to which they can aspire after the drug treatment session. But there may be more to it than that, because the increased synaptic flexibility produced by 5-HT2A receptor stimulation in preclinical models may allow the brain to reset itself into a different, depression-free, state. Another possibility shown by fMRI connectivity analysis is that psilocybin may alter the pattern of dominant connections between frontal cortex and subcortical regions such as the amygdala.

There is now good conceptual evidence that the antidepressant effects of psychedelics are mediated in quite a different way to those of serotonin-acting antidepressant drugs such as the SSRIs. The latter seem to provide a buffer against stress by enhancing serotonin function at the 5-HT1A receptor, so making the person more resilient. In contrast we believe that the psychedelics acting via stimulation of the 5-HT2A receptor work to reset the brain processes, eg, overconnected DMN that underpins the depressive thinking and so allows the patient to work through their issues and so overcome their depression. It appears that activations of these serotonin receptors can have profound and long-lasting effects on brain function that might explain why a single dose can lead to antidepressant efficacy for weeks or months. However, for most of our patients the depressed ideation began to re-emerge by 6 months. So in our ongoing study of psilocybin versus escitalopram we are giving a second psilocybin dose 3 weeks after the first to explore if more enduring activity might be produced.

MDMA works quite differently; it is a serotonin-releasing agent and fMRI studies have revealed its main activity as being in the limbic system where it suppresses activity especially of amygdala and hippocampus. We believe that it is this damping down of the emotional memory circuits that helps patients with PTSD relive their traumas and at the same time overcome and eventually extinguish the intense emotions that go with the memories of them.

We cannot finish a review of the psychological effects of psychedelics without mentioning microdosing. This has become a topic of general discussion, especially in people working in the creative industries, many of whom claim to use low, ie, subpsychedelic doses, of psilocybin or LSD to aid their mental processes. Some claim that this helps with their mood and may keep depression at bay. These doses are taken regularly, usually a couple of times a week. However, since these drugs are illegal there is no way of knowing for sure what they are and what exact doses are being used. Also there are no controlled trials so the effects could all be suggestion or placebo. Still, it is pharmacologically plausible that some low-level activation of the 5-HT2A receptor from a microdose might alter brain function in a positive creative way, and research into this possibility is urgently required.

*From the article here :
 
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Mechanisms Underlying the Therapeutic Effects of Psilocybin*

by CBT-I | October 2019

Recent controlled studies on psychedelics at major medical centers including Johns Hopkins, NYU, and UCLA have reported groundbreaking results for the treatment of psychiatric disorders. In studies using psilocybin for treatment-resistant depression and major depressive disorder, improvement and remission rates are double or triple those of SSRI medications after just one treatment session. Because these are unprecedented improvements over currently available therapies, the FDA has designated psilocybin for treatment-resistant depression and major depressive disorder as a rare "Breakthrough Therapy." Psilocybin is also being tested for the treatment of addiction and cancer-related depression and anxiety.

Although psychedelics can also produce a range of negative experiences including anxiety, controlled studies have shown that psilocybin occasions experiences similar to spontaneously occurring mystical experiences in the majority of patients, with corresponding improvements in personality that may be permanent. Michael Pollan, in his recent New York Times Bestseller How to Change Your Mind, has written about the potential of psychedelics for transformation and transcendence.

What are the therapeutic mechanisms underlying the effects of psychedelics that result in mystical-type experiences in the majority of patients? This is an important question for explaining the therapeutic effects of psychedelics in lay terms for patients and clinicians undergoing this novel therapy.

The dramatic therapeutic effects of psychedelics may be understood in part from a synthesis of recent research in three related areas of affective neuroscience: the Default Mode Network and the ego, the core-affective Self, and the neurobiology of psychedelic states of awareness.

The Default Mode Network and the ego

The Default Mode Network (DMN) is a core brain network that is active in the conscious resting brain. It exhibits persistent and vigorous brain activity that deactivates when the brain is directed toward a task or goal. The DMN represents the default baseline state of the awake brain when the eyes are closed and individuals are engaged in internally focused tasks like autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. These tasks cause the DMN to consume a high amount of the brain’s energy during its default resting state. Reading or other routine tasks require minimal additional energy over what is already consumed by the DMN. Because the DMN receives more blood flow and consumes more energy than other brain region, and is a center of dense connectivity, it serves as an important “connector hub” for information integration and routing in the brain.

The DMN is thought to deal with introspection, memory and other "inner" processes, in contrast to other brain regions that respond to the environment and what happens in it. The DMN allows individuals to mentally simulate the past and future and infer the mental states of others. Instead of being psychologically constrained to the here-and-now, the DMN allows us the unique ability to disengage from the external world and turn our thoughts inwards to construct mental simulations of hypothetical scenarios that allow us to anticipate and evaluate future events. Through this mental simulation of our past, future, and the minds of others, we travel far beyond the observable. As a consequence, we spend a lot of time thinking not about what is going on around us, but about events that happened in the past, might happen in the future, or will never happen at all. Although this ability is a remarkable evolutionary cognitive achievement that allows us to learn, reason, and plan, it comes at an emotional cost. Many philosophical and religious traditions teach that happiness is to be found by resisting mind wandering and the internal monologue and, instead, living in the moment and “being here now.”

The DMN’s metacognitive processes include:the internal monologue (“the voice in our head”), mind wandering and day-dreaming; autobiographical memory; an actively created, learned perception of time; mental time travel into the past and future and imagining hypothetical events and scenarios;theory of mind (the ability to infer what others are feeling or thinking) and the generation of narratives about ourselves that help create a stable sense of Self over time. Because the DMN is primarily responsible for internally focused, self-reflective processes, it is the neurobiological orchestrator of the conscious Self, the ego.

The DMN also filters sensory stimuli impinging upon the brain. Because the brain is continually bombarded by a significant number of external stimuli such as vision and sound, and internal stimuli such as emotions and thoughts, we would be overwhelmed unless the brain had a filtering mechanism to determine what reaches conscious awareness. The filter is a function of selective inhibition by the DMN that is energy-demanding. This inhibition, which is reflected in the highly active resting baseline default state of the brain, occurs at the level of cortex by the DMN’s top-down control. The DMN also exerts its inhibitory filtering influence at the level of the thalamus and reticular formation, two lower brain areas that play a central role in alertness, attention, and consciousness. Central to the DMN’s thalamic/reticular filter is habituation, the process by which the brain learns to consciously ignore safe, repetitive stimuli while consciously attending to more important, novel stimuli. Through this mechanism of restriction and reduction, the DMN controls the gates of awareness by deciding what reaches conscious awareness or stays unconscious.

The DMN may have come online as recently as 40,000 years ago when we see the first widespread evidence of self-conscious, symbolic thinking and mental time travel in the art of Cro-Magnon man. It was here that we emerged from the primary affective consciousness that we shared with animals and become truly modern humans: problem solvers, artists, inventors of ritual and technologies, possessors of an aesthetic consciousness, and creatures of intelligence and complexity.

As our conscious Self, the ego edits and limits our personal awareness by regulating the DMN’s filtering process. Chief among the ego’s editing functions isto maintain the boundary between the conscious and unconscious realms of the mind, as well as the boundary between Self and other objects. Experience cannot enter awareness unless it can bypass this filter, which is selective and socially conditioned based on society and culture, language, and science. The ego’s filter is constructed in light of our past experience, needs and desires, biases, wishes and fears, likes and dislikes, and expectations. It is characterized by active control and manipulation of the environment, sequence and order, rationalism and materialism, causes and effects, beginnings and ends, and a created sense of time. The ego creates a relatively stable personal reality and sense of Self through this selective awareness and attention.

The hallmark of the ego is the subject-object relationship,in which differences are seen by categorizing the world as either “I” or as objects separate from “I”. All objects are things to be analyzed, evaluated, explained, and compared to create our social definition of self-identity and the stories we tell ourselves about who we are: how much we earn and own, how attractive and successful we are, and what our roles are at work and at home. Being right, resentment, coveting, possessing, acquiring, status, material possessions, and power are all products of the ego’s subject-object dichotomy.

The ego may have come online as recently as 10,000 years ago, coincident with the development of agriculture, as a subject-object interface for a world view that began to involve control over nature and ownership of plants and animals. Although the natural and social worlds were previously integrated into a cyclical, rhythmic world that included humans, animals, plants, and objects to for man animistic, living nature, we began to see the world in terms of the subject-object relationship, causes and effects, beginnings and ends, and the importance of an explanatory nature of events. Through writing, philosophy and the beginnings of science, we rapidly progressed to the age of reason, the industrial age and the invention of time, and finally to the computer age. The ego and science have become our sole arbiters of reality.

Eastern traditions teach that the ego reduces and restricts information from conscious awareness and blocks perception of a more comprehensive awareness of ourselves, others, and the world. Instead of hearing and seeing what truly exists, we see things through the ego’s distorting, thought-based filter. We are not our ego identity or social role, and awareness of our Self as a separate entity from objects increases our sense of existential isolation.

The Core-Affective Self

Whereas the DMN and ego form the hub of our conscious rational Self, the core of our affective Self lies in more ancient, unconscious brain regions. These neural territories below the cortex are the primordial affective systems shared by all mammalian brains. From these systems we inherit emotions as evolutionary, unconscious tools for living. As the affective foundations of our mind, emotions are built into the brain by evolution as archetypal genetic memories held in common as the evolutionary wisdom of our collective ancestral past.

Converging neuroscientific evidence involving emotional processes in ancient brain regions supports the concept of a Core Affective Self (CAS) as an innate, primordial Self. Jaak Panksepp, a pioneer in affective neuroscience, postulated that the CAS and its pure form of affective consciousness interact with higher rational cognitive processes to form the neural foundation for all emotional experience. Although higher cognitive forms of self-consciousness emerged in the neocortex, they were built upon an evolutionary foundation of ancient brain regions and their affective consciousness. Because emotions lie at the core of our beings, they may constitute an essential foundation for the evolution of higher, more rational forms of consciousness.

According to Panksepp, the CAS is a highly evolved element of the mammalian brain that is preserved through species rather than being unique to humans, yielding a trans-species concept of Self. It is a primordial affective consciousness that experiences emotional feelings. And because feelings may have been the first sources of consciously felt experience in the mammalian brain, the CAS may have been the first form of consciousness that evolved on earth. It infinitely precedes our cognitive understanding of the world and has the power to feel and the capacity for pure experience,without the capacity to reflect on the experience. Although not self-conscious, the CAS is an innate intelligence that has an internally felt,unified presence in the world. It is an underlying dimension that represents a unitary reality and a non-reflective consciousness. Because it evolved long before the recent emergence of the DMN and the ego, the CAS does not see itself as the subject with all other objects as separate and to be acted upon. But once the DMN and the ego came online, the CAS and its affective consciousness were inhibited and repressed into the unconscious.

Carl Jung believed the organizing system of the Self is predominantly affective and archetypal, and must lie subcortically in the brain stem. He conjectured that such a subcortical affective system might reflect a symbolic, pre-verbal archetypal form of the unconscious that is contained in the brain of all individuals as the collective emotional unconscious. It holds the totality of all human experience back to its remotest beginnings and contains the whole spiritual heritage of man’s evolution. The collective unconscious is identical in all individuals throughout history and cultures,and is inherited and independent of the individual: a universal mind that may be synonymous with the Core-Affective Self.

Panksepp postulated that the CAS’s primordial form of conscious affective experience emanates from the brain’s emotional control center: the periaqueductal grey (PAG). The PAG is the most ancient and highly concentrated emotional convergence zone in the brain and is located in the upper brainstem. It is the grand central station of emotion because it is involved in all emotions, not just fear like the amygdala. It also has the most massive convergence of brain systems and can induce the most powerful emotional changes in the brain. Damage to it causes greater impairment in consciousness than any other areas of the brain, suggesting that it is crucial for consciousness. The thalamus and reticular formation, which play a key role in the DMN’s filtering mechanism, lie adjacent to the PAG.

The neurobiology of psychedelic states of awareness

Psychedelics are associated with increased networking between otherwise disconnected areas of the brain, particularly ancient levels of the brain. They also reduce connectivity between areas of the brain that comprise the DMN, thereby suppressing and disabling it. This inhibition of the DMN and its normal top-down and thalamic/reticular filtering process produces several profound effects on awareness that result in an altered state of consciousness.

A common, yet extraordinary, effect on awareness is the inhibition of the ego’s habitual, automated filtering of perception. This is experienced as a more direct state of awareness that “mirrors” sensory stimuli rather than filtering and distorting them. We “see” and “hear” rather than think and filter, and we perceive directly instead of interpreting and analyzing. The senses and perceptions are described as keener and richer, and the world looks new and vivid. There is an intuitive sense of realness and ineffability. The voice in our head ceases, acquired beliefs are stripped, and the world is seen with the innocent eye of a child in a state of wonder. The horizon of awareness is perceived as greatly expanded, as if a veil was pulled aside,and one is often left with the unmistakable feeling that one has perceived the true essence of things.

Another common and profound effect on awareness is a breakdown of subject-object boundaries as the ego becomes less real or disappears. Instead separating and analyzing objects in terms of use and purpose, the Self and objects merge. The ego’s constructed sense of time ceases to exist and awareness profoundly merges with the present. Objects are seen for the first time without the distortions of needs, wishes, uses, or purpose, and there is a profound realization that we are more than our ego identity. An integral connection with the environment is experienced and objects are perceived as a part of a connected, unified whole. Inanimate objects are perceived as alive and personal, and animism, mystery and divinity are perceived in ordinary phenomenon. The ego’s anxieties and fears, needs and desires, likes and dislikes, and sense of isolation are replaced with openness, trust, confidence, and feelings of compassion and empathy toward one’s Self and others. Unconscious emotional stimuli are also disinhibited from ancient brain systems and flood conscious awareness. By gaining access to these unconscious emotional stimuli that significantly affect our conscious perceptions and behaviors, including memories, worries, fears, and conflicts, they can be re-appraised consciously in an accepting, compassionate, ego-free state.

These dramatic changes in awareness, which would be considered miraculous in psychotherapy, constitute the core-affective experience that commonly underlies psychedelic states of awareness.

The Core-Affective Self and Transcendence

When psychedelics occasion a mystical-type experience, it is consistent with a disinhibition of the CAS from ancient brain regions.This primordial territory of awareness precedes language and the ego and exists in the unconscious as a genetic memory. It represents an archetypal, collective affective consciousness that is available as a universal dimension of human awareness but is rarely accessed because it has been inhibited and repressed into the unconscious. The CAS is imbued with an ancestral sense of timelessness and oneness and is perceived as an innate, intuitive intelligence.

The conscious experience of the CAS often produces ineffable feelings of illumination and insight not previously experienced by the ego, and the unmistakable sense of authority and durability of objective truth that is beyond explanation, yet comprehensible. Eastern traditions consider this state of awareness the highest, most direct state of consciousness because it transcends the ego. It is perceived to be a collective unity shared by all that allows the individual to see the true essence of the Self.

The initial anxiety from the ego dissolving is followed by feelings of being transported into a new reality of self-transcendence as the boundaries of the Self greatly expand and the CAS becomes conscious. The hallmark descriptions of this experience are awe, joy, oneness, grace, and bliss. So transcendent is this experience that it is described as a majestic, sacred, miraculous, unfathomable reality that is hidden from everyday sight. Feelings of emotional communion, oneness, and a spiritual epiphany are commonly reported. The experience is often described as being re-awakened and touched by one’s higher Self. Universally across psychedelics, cultures, and time it is described as a feeling of cosmic union, reverence, humility, grandeur, or rapture that mirror reports of mystical experiences in the major religions and annals of history. Known as the awakening of the Self in mystical traditions, the exact time and place of this rebirth are remembered for the rest of life as the moment the ego surrendered to a higher, sacred truth.

This transcendent experience becomes a powerful emotional memory of what lies below the surface of everyday awareness. It promotes a deep assurance of meaning and divinity, alters perception of one’s Self, others and the world, and produces permanent improvements in personality and well-being. The result is a more integrated mind that strikes a greater balance between affective and rational consciousness, ego and Core-Affective Self.

*From the article here :
 
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How do American psychiatrists view psychedelics?

by Dax Oliver, MA | PSYCHEDELIC SUPPORT | 19 Nov 2020

Although a majority of American psychiatrists still view psychedelics with worry, many seem open to their potential according to a study by Barnett et al. Interesting differences in opinion also emerged based on age, gender, and professional status. As new psychedelic research continues to be published, can we draw any conclusions?

How do American psychiatrists view psychedelics? It’s complicated. Although a study by Barnett et al. said that a majority still seemed leery, a “large minority” appeared optimistic about their potential.

For example, considering psychiatric disorders, 65 percent of survey respondents thought that psychedelic use increased the risk, yet 81 percent thought it deserved further research. Nearly the same percentage thought that psychedelic use “shows promise in treating psychiatric disorders” (43 percent) as “increases the risk for long-term cognitive impairment” (48 percent).

The Barnett et al. study examined survey responses from 324 members of the American Psychiatric Association (out of 1000 surveys requested). It focused on relatively older psychedelics (such as LSD and psilocybin), as opposed to more recent psychedelic compounds (such as MDMA and ketamine). The study also used the term “hallucinogen” instead of “psychedelic.”

The overall percentages of study respondents who moderately or strongly agreed with the survey’s seven statements can be seen here:

The study authors had previously wondered if psychiatrists might be more suspicious about psychedelics than average Americans, since they’re sometimes on the front lines of dealing with negative psychedelic experiences. Yet the authors found that opinions of the survey respondents “seemed to parallel those of the general public,” which have also been leery but slowly growing more open. Suspicion among psychiatrists might also mirror some lingering negative opinions about psychedelics in the American media.

It could be encouraging that relatively few psychiatrists thought that psychedelics were “unsafe even under medical supervision.” Perhaps talking with therapists trained to supervise psychedelic treatments would open more minds. Since the number of therapists with psychedelic training has been increasing around the world, that type of interaction might be happening more often.

Interesting demographic differences emerged in the Barnett et al. study. The results for each demographic that had significant results can be viewed in the charts below. Click on the buttons to see the results for each demographic.

About these demographic differences, Barnett et al. wrote: “Male and trainee respondents, as compared with female and attending respondents, reported less concern about the risks of hallucinogens and greater optimism about their therapeutic potential. Younger psychiatrists also seemed more optimistic.”

Barnett et al. thought that personal experiences might have been a contributing factor in these differences. They noted that "according to the National Survey on Drug Use and Health, men have reported roughly twice the lifetime prevalence of hallucinogen use as women did.” This didn’t mean that male survey respondents in the Barnett et al. study were more likely to have used psychedelics themselves, but it might have suggested they knew more people who had safely tried psychedelics. However, the study authors were careful to emphasize that they did not ask participants about personal psychedelic use in order to avoid privacy concerns.

The study thought that higher optimism among trainees and younger psychiatrists might have been due to recent exposure to positive articles and studies about psychedelics. In addition, trainees and younger psychiatrists might have had few experiences with the types of negative stories so widely distributed in the 1960s.

Those positive articles and studies have been coming rapidly recently. For example, this month saw the release of a major new psilocybin study in JAMA Psychiatry, which stated that “psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder.” The previous few months also brought two other positive articles in JAMA Psychiatry, one about “The Current Status of Psychedelics in Psychiatry” and an editorial about “Psilocybin-Assisted Supportive Psychotherapy in the Treatment of Major Depression – Quo Vadis?”

The November 2020 election legalized psilocybin therapy in Oregon and decriminalized psilocybin in Washington D.C. Other communities, such as Denver, Oakland, Santa Cruz, and Ann Arbor had already decriminalized psilocybin. You can read more about decriminalization and legalization efforts around the United States here. Perhaps the illegal status of psychedelics and the long stigma attached to psychedelic research could be contributing to suspicions among psychiatrists. It might be interesting to see if these attitudes change in places where psychedelics have been legalized or decriminalized. A survey about ketamine might already show some of these effects, since it can be legally prescribed throughout the United States.

How do American psychiatrists view psychedelics? Like the rest of the United States, they seem to be in flux. There are signs of growing interest and openness to psychedelic therapy, but in general, Barnett et al. noted that “American psychiatrists seem to remain concerned about the possibility of adverse psychiatric and neurocognitive effects from hallucinogen use.” As more studies are published and psychedelic therapy becomes more available, perhaps that concern will start to wane.

 
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The power of psychedelics

by Erica Rex | Scientific American | 12 Jul 2020

They worked for my depression. Could they be the future of psychiatry?

In 2012, I had my first psychedelic experiences, as a subject in a clinical trial at Johns Hopkins University School of Medicine’s Behavioral Pharmacology Research Unit. I was given two doses of psilocybin spaced a month apart to treat my cancer-related depression.

During one session, deep within the world the drug evoked, I found myself inside a steel industrial space. Women were bent over long tables, working. I became aware of my animosity towards my two living siblings. A woman seated at the end of a table wearing a net cap and white clothes, turned and handed me a tall Dixie cup.

“You can put that in here,” she said. The cup filled itself with my bilious, sibling-directed feelings. “We’ll put it over there.” She turned and placed the cup matter-of-factly on a table at the back of the room. Then she went back to her tasks.

Whenever I speak with her, Mary Cosimano, the director of guide/facilitator services at Johns Hopkins Center for Psychedelic and Consciousness Research, mentions the women in the chamber and the cup. My experience struck a chord. For me, the women in the chamber have become a transcendent metaphor for emotional healing.

“I’ve thought about having a necklace made, with the cup, as a momento,” she said the last time I saw her at a conference. “Have you thought about it?”

Prior to their 1971 prohibition, psilocybin and LSD were administered to approximately 40,000 patients, among them people with terminal cancer, alcoholics and those suffering from depression and obsessive-compulsive disorder. The results of the early clinical studies were promising, and more recent research has been as well.

The treatment certainly helped me. Eight years after my sessions, researchers continue to prove the same point again and again in an ongoing effort to turn psychedelic drug therapy into FDA-sanctioned medical treatment. This can’t happen soon enough.

“Psychopharmacology as a field had stalled. Many patients don’t respond to conventional treatment with SSRIs,” says Charles Grob, M.D., professor of psychiatry and biobehavioral Sciences at Harbor-UCLA Medical Center, and the first modern clinical researcher to treat advanced-stage cancer patients suffering from depression and anxiety with psychedelics.

There is little hard evidence to show that long-term psychotherapy is effective in treating mental illness, depression or post-traumatic stress disorder (PTSD). And there’s the cost, which fewer and fewer insurers underwrite and ordinary people can’t afford.

The failure of the psychotherapeutic process is located at its epicenter: the power disparity in the therapeutic dyad. Merely walking through the consulting room door, the patient subordinates herself to the therapist, who, by virtue of a title, is presumed to know more about her than she does herself. Transference and countertransferance—offspring of Freudian psychoanalysis—are cogs in the same moribund engine. The field will not change until the therapeutic relationship as it has been structured since the 19th century disappears.

Psychedelic drug therapy subverts the timeworn patriarchal hierarchy by creating an atmosphere of cooperation and trust rather than competition and domination. Or, to state it more bluntly, what women do in structured settings rather than what men do; women create cooperatives, men create hierarchies.

The treatment space is furnished like a lounge, with couches, chairs and table lamps. A music track plays. Two trained guides, one male, one female, are seated close by, ready to help if the emotional path becomes difficult. Guides are not therapists; instead they serve as trusted companions along a perilous, transformative spiritual journey. The sessions are led by the subject herself, by her feelings and perceptions throughout the experience and the way she processes them afterward.

“The drug is a skeleton key which unlocks an interior door to places we don’t generally have access to,” says psychologist William Richards, one of the researchers who successfully treated patients with hallucinogens in the 1960s and early 1970s. “It’s a therapeutic accelerant.”

MDMA (3,4-methylenedioxymethamphetamine) is rapidly proving effective in treating PTSD. MDMA is an “entactogen”: it touches within in a way talking does not. Michael Mithoefer, a psychiatrist in Charleston, S.C., who has worked with military personnel and first responders, conducted a phase II clinical trial using MDMA to treat PTSD.

“Treatment is not just revisiting the traumatic experiences,” he said. “It’s a process of affirming a different experience on all levels, including in the body.”

During MDMA sessions, subjects become more emotionally flexible and able to stay the course while exploring difficult memories. Many experience an enduring change in their response to emotional triggers. Clinicians hope to see MDMA approved by the FDA for PTSD treatment as early as 2022.

Treatment with psychedelic drugs represents a paradigm shift in the approach to mental health. For me, the change in the field is embodied by the presence of the busy women along my journey. The women treated my feelings as matters of fact, not to be avoided, reviled or fled from, but so obvious and ordinary they could be poured into a Dixie cup and set aside.

The success of the cancer studies has led to investigational treatment for patients suffering from intractable depression, early-stage Alzheimer’s, anorexia nervosa and smoking addiction. Within a few years, the patriarchal therapeutic model could be a thing of the past, supplanted by short-term guided treatment with psychoactive drugs.

 
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Why psychedelic drugs are entering the world of psychiatry

by David Smiedt | GQ | 27 Aug 2018

A group of medical researchers are challenging the stigma around mind-altering substances – and discovering they could hold the key to tackling a whole range of mental health issues.

At any given time, there’s a mere handful of people truly tapped into the zeitgeist. In music right now it’s Kendrick Lamar; in fashion Virgil Abloh; in film it’s Dwayne Johnson.

You can add author Michael Pollan to the list. His 2006 book The Omnivore’s Dilemma was part of a seismic shift in which readers and eaters began questioning where their food came from, how it was produced and who was fucked over along the way (the farmers, the animals, the planet) in order to get it to your plate.

By the time the 10th anniversary edition was released, it had sold more than two million copies. But this year, he shifted his focus from the stomach to brain with How to Change Your Mind – The New Science of Psychedelics and cemented his rep as a writer at the very edge of public consciousness.

The starting point was the concept of microdosing – a red-hot trend in Silicon Valley and beyond – where the most lateral of thinkers are taking small amounts of LSD, which generate ‘subperceptual’ effects that can improve mood, productivity and creativity.

A smart drug for smart people, if you believe the hype.

Pollan characteristically built on this by replacing the microdosing with macrodosing. By which we mean he took drugs. Many, many drugs. In quantities that make people, according to the New York Times, “feel the colours and smell the sounds”.

Whether or not he knew it at the time, he ever so slightly wedged open the doors of perception when it comes to psychedelic drugs and their potential benefits. In so doing, he has tapped into a burgeoning movement in which, primarily, ‘recreational’ drugs, such as LSD, mushrooms, marijuana, ketamine and MDMA, are showing glimpses of clinical promise where conventional medications are not.

It’s in the field of mental health that the results are most apparent. Which is just as well because for all the increasing openness we have about discussing this scourge, the numbers are not decreasing. Quite the opposite.

In April this year, mental-health technology group Medibio polled 3500 Australian workers from 41 organisations across a range of industries and found that 36 per cent had depression and 33 per cent had anxiety. In contrast, the 2007 stats list anxiety at 14 per cent and depression at six per cent.

A part of this leap is undoubtedly down to the fact that people are more comfortable discussing these issues and seeking help. That’s a very good thing. However, it’s equally clear that the current approach of counselling combined with the most common medications – selective serotonin reuptake inhibitors (SSRIs) like Lexapro – doesn’t work for everybody.

Nothing does and nothing ever will, but in labs around the world, the go-to party drugs for everyone from bush-doofers to EDM aficionados are throwing up results that are beginning to overshadow their tarnished reputations.

One of these is MDMA, which was invented in 1912 by a German pharmaceutical company to help medications that control bleeding. It first entered the dance party scene in the mid-’80s and quickly became as much a part of these events as tolerating Armand Van Helden, gurning wildly and finding conversations with complete strangers to be fascinating.

Manufactured under dubious circumstances at best, there are clearly risks involved with recreational use. But transfer the setting from club to clinic and a different picture emerges. Especially as a potential treatment for people with post-traumatic stress disorder (PTSD). In a study conducted by the Multidisciplinary Association for Psychedelic Studies (MAPS) in the United States, 56 per cent of 107 subjects no longer qualified for PTSD after treatment with MDMA-assisted psychotherapy, measured two months following treatment.

At the 12-month follow up, 68 per cent no longer had PTSD.

“Most subjects received just two to three sessions of MDMA-assisted psychotherapy. All participants had chronic, treatment-resistant PTSD, and had suffered from PTSD for an average of 17.8 years,” says MAPS director of strategic communications Brad Burge.

A separate study conducted this year by the Medical University of South Carolina on an admittedly small group of 26 first responders and military personnel concluded, “Active doses (75mg and 125mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well-tolerated in reducing PTSD symptoms.”

There’s a bit to unpack in these qualified conclusions, most notably the terms “with adjunctive psychotherapy” and “controlled setting”. “It’s important to keep in mind that MDMA will not be a take-home drug,” says Burge. “MDMA-assisted psychotherapy is a supervised treatment – it happens in a clinic or therapist’s office, with a medical review and therapeutic supervision. This is not ‘take two and call me in the morning’. Patients would never get a prescription for MDMA to fill themselves at the local pharmacy. Unlike all other medications for PTSD, with MDMA-assisted psychotherapy, patients only take the drug two or three times over a 10-week course of psychotherapy – and research suggests that the benefits last.”

He adds that "though the drug has side effects such as possible anxiety, lack of appetite, increased body temperature and nausea for the four to six hours it’s in your system," Burge says, “They are not as extreme or long-lasting as SSRIs” which millions of Australians take daily. “Also, nobody in the completed trials reported dependence or continued use of MDMA after participation in the trial.”

MDMA’s benefits are, according to Burge, not restricted to the treatment of PTSD. “It has also shown promise in early research as an adjunct for psychotherapy for anxiety associated with life-threatening illnes and social anxiety in autistic adults. It is now [also] being studied in alcoholism treatment as well as cognitive-behavioural conjoint therapy (aka couples therapy).”

At the very least, he expects it to be approved by the US Food and Drug Administration for PTSD therapy by 2021.

Closer to home, Dr Gillinder Bedi, a senior research fellow at both The University of Melbourne and Orygen, The National Centre of Excellence in Youth Mental Health, advocates a cautious approach in the MDMA-as-therapy debate.

“The slow progression of MDMA-assisted psychotherapy from the subcultural margins towards approval has been driven by the belief of those advocating for it,” she says. “Without this motivated community, MDMA would likely not have been developed as a medication. The downside of this robust advocacy base is that it can lead to rather extreme claims, such as being labelled ‘penicillin for the soul’. In addition to well-designed studies that control for experimenter bias, there is a need for researchers and clinicians outside the MDMA-advocacy community to be involved in the ongoing development of this research direction.”

Clearly there are more questions than answers right now, many of them practical. “For instance, should prescribing be limited to physicians with specific qualifications?” asks Bedi. “What training should be required for those conducting the psychotherapy? How should the drug be handled and stored by pharmacists? This suggests a need for stringent training and oversight of MDMA-assisted therapy.”

Then, there’s the proven human factor where not everyone will play by the narcotic rules. Case in point: Modafinil.

A report by the University of Melbourne’s Brain, Mind and Markets Laboratory found that the anti-narcolepsy drug was the go-to helper for certain finance professionals and students who want to maintain their focus during long hours in the library or plundering the markets. Some is sourced online. Some comes from Australian doctors in a trend known as off-label prescribing. And if Modafinil – known as ‘Viagra for the mind’ – is in demand, wait until your local GP has pure Molly at his or her disposal.

“Approval of MDMA will lead to off-label prescribing, with doctors prescribing the drug for conditions other than PTSD,” says Bedi. “This could include a range of conditions, such as depression and substance-use disorders.”

This is just one of myriad red flags. Burge says MDMA’s therapeutic acceptance has been hamstrung by several additional factors. “Recreational use and abuse has been one source of the stigma, but an even greater cause of the stigma has been the misinformation, bad science, and political posturing that policymakers have engaged in for decades,” she says.

In political terms, the issue of psychedelics as therapy is an easy knee-jerk for neo-cons.

‘This government is spending your tax money on street drugs’ is a convenient and divisive headline, sure to prompt enough harrumphs across the media landscape. There have also been enough tragic high-profile cases, such as that of Sydneysiders Anna Wood and Sylvia Choi – both of whom died after taking ecstasy at dance parties – to place the discussion forever on the back burner. Strike one.

In response, researchers likes Burge are quick to point out that there is a monumental difference in the purity and dosage of the MDMA being sold on the street (and cut with any number of harmful fillers) compared with that used in clinical studies. Then, there’s the financial factor. Specifically, the issue of patents, which tend to run to 20 years in the pharmaceutical industry.

The theory goes that this amount of time generally allows the manufacturer of the drug to recoup their R&D costs and accrue a reasonable profit before generic, lower-cost varieties are made available to the public. The problem, as far as big pharma is concerned, is that the patent on MDMA ran out some time before World War II. Which means that any significant potential turnover arising from exclusivity is immediately off the table. Strike two.

What’s more, unlike your standard SSRI anti-depressants, which require ongoing use (and is therefore more profitable), many of these patent-free psychedelics need only a handful of doses to provide relief. With both potential volume and profit thus diminished, Burge says you have distinct “lack of interest” on the part of for-profit pharmaceutical companies. Strike three. Attitudes are slowly changing in the pharmaceutical community and Burge is confident that “within the next 10 years, we’ll see psychedelics enter psychiatry as the first new class of psychiatric drug in the last 30 years”.

However, it’s unlikely that many Australians will be able to access legal therapeutic MDMA any time soon. Considering how long it took to convince them of the medicinal benefits of marijuana, no local politicians are waving the psychedelic flag just yet. Those who might benefit right now have to be lucky enough to qualify for one of the few small local clinical trials.

In this respect, organisations the Sydney’s Black Dog Institute are creating some world-firsts but these options are still few and far between. Writing in April’s Australian Psychologist journal, doctors Stephen Bright and Martin Williams warned that Australia was being left behind the rest of the world on the research front. Bright noted that there is “a lot of academic conservatism” in Australia towards research involving drugs which are best known as illegal stimulants, adding that there was “a vested interest in maintaining the current paradigm”.

And it’s not just MDMA in the firing line. Everyone’s favourite horse tranquiliser, ketamine, is also prompting words like “astounding” from medical researchers not given to hyperbole. In 2016, the University of New South Wales’ Professor Colleen Loo began a randomised double-blind three-year trial into the effectiveness of the drug as a depression treatment for people who have not responded to other medications.

The 16 subjects were all over 60 and Loo found that half showed no signs of depression after a single dose. “I was a bit sceptical with all the reports coming out from overseas,” Loo told Triple J, “I thought, ‘I’m just not sure if I believe this, it’s unbelievable’. And I must say, the first person we treated – I still remember the very first person – he and I looked at each other and he said, ‘I don’t believe it’, and I said, ‘Neither do I’. He’d been depressed for literally 10 years and had failed more than 10 medications. He said, ‘The fact I can receive one treatment and be well after one day is just unbelievable’.”

A 25-year-old speaking under an assumed name told the same program that after 10 years of living with depression he “felt backed into a corner and held hostage to depression that I didn’t want to be fighting so much anymore”.

In an approach guaranteed to alarm psychedelic proponents and provide ammunition to critics, he bought some ketamine off the dark web and began experimenting. Successfully, it turned out. “My life outlook is much more positive now,” he said. “It’s allowed me to take back my life in a sense. From years of having to put life on hold, I found that it was a lot more worthwhile and cost-effective than spending my life on antidepressants.”

Much like MDMA, the popularity of ketamine on the black market makes it vulnerable to exploitation and misuse – which is why almost every researcher GQ interviewed spent a great deal of the conversation issuing caveats.

Yet, away from the world of dance parties and K-holes, it has the potential to save lives in the most immediate and drastic sense of the term. In the first study into esketamine (a part of the ketamine molecule) conducted by a drug company (in this case Johnson & Johnson) with Yale University, 68 people at risk of imminent suicide were treated with the drug. The authors found it not only led to a “significant” improvement in depressive symptoms within 24 hours but also leveled off at around 25 days – which is roughly the time it takes for antidepressants to kick in to full capacity in the body.

Commenting on the data, England’s often-conservative Royal College of Psychiatrists said that it brought the drug “a step closer to being prescribed on the NHS”. Because Australian doctors have access to ketamine as an anaesthetic and pain reliever, authorities fear it too may be prescribed ‘off label’ without enough research into the long-term consequences (if any) of its use in suicide prevention.

Israeli-American writer Ilana Masad was given ketamine by her psychiatrist in an attempt to counter her stubborn depression. Writing for The Fix, an online publication devoted to addiction and recovery, she revealed, “Shortly before my first ketamine treatment, I became suicidal for the first time in my life. If I hadn’t started ketamine treatments when I did, I don’t know whether I’d be here writing this article now.”

While the likes of MDMA and ketamine made their way into public consciousness from the ’80s onwards, those wanting to take a trip in the psychedelic ’60s turned to LSD.

‘Acid’ is also experiencing its own contemporary resurgence and according to an analysis published in the Canadian Medical Association Journal, there are studies being done on the use of lysergic acid diethylamide as a treatment for post-traumatic stress disorder and anxiety.

A more natural alternative may be found in psilocybin – the active hallucinogen in magic mushrooms. Johns Hopkins University researchers gave the drug to 51 cancer patients also suffering from mental-health issues like anxiety or depression. Six months on, it was found that about 80 per cent of participants continued to show clinically significant decreases in depressed mood and anxiety, with about 60 per cent showing symptom remission into the normal range.

Researchers stressed that the drug was given in tightly controlled conditions in the presence of two clinically trained monitors and said they do not recommend use of the compound outside of such a research or patient-care setting. But what’s most astounding about this was that the results were again achieved in a single dose.

Another natural compound, ibogaine, is also gaining clinical attention. A psychoactive found in plants from the Apocynaceae family, it’s being examined as a potential therapy for those battling drug dependence.

Make no mistake; this is dangerous gear with severe side-effects including hallucinations, seizures, fatal heart arrhythmia and brain damage in patients with prior health problems. In 2014, 33-year-old West Australian Brodie Smith died on the first morning of what was supposed to be a four-day ibogaine treatment program in Thailand. He was trying to kick his dependence on illegal drugs. And yet, there are several studies that suggest that ibogaine, under appropriate conditions, could well be a habit-breaker.

As reported in Scientific American, in May 2016 a meta-analysis examining 32 studies, mostly in mice and rats, found that ibogaine reduced self-administration of cocaine, opioids and alcohol.

An earlier study from 2015 discovered noribogaine, the substance that ibogaine breaks down to when ingested, reduced self-administration of nicotine in addicted rats by 64 per cent.

Californian company Savant HWP has now progressed to secondary trials for a synthetic ibogaine compound, called 18-MC, which mimics the anti-addiction properties without the trippy side-effects. The potential benefits for Australia are obvious as opioid prescriptions here increased from 10 million per year in 2009 to 14 million per year at the end of 2017 – that is an increase of 40 per cent over the past eight years. Worth a look, then.

With new applications and (again) appropriate safeguards for once demonised substances, be they chemical or naturally occurring, in place, Burge believes we are on the threshold of a giant leap forward in the way we treat our troubled minds and bodies.

If Australia’s growing acceptance of marijuana as a legitimate treatment in palliative care, epilepsy, chronic pain and multiple sclerosis is anything to go by, it’s clear that we are no longer as attached to the notion that because a drug can be misused it should automatically be sidelined and vilified.

“The resistance to this notion is definitely fading,” says Burge, “and it fades more with every new study that’s completed. Researchers from multiple organisations and institutions around the world are showing real therapeutic benefits from psychedelic-assisted therapy, especially MDMA and psilocybin and also ibogaine, for specific mental-health conditions. That data, and the overall very supportive attitude of policymakers and regulators around the world, are resulting in what’s been called a renaissance in psychedelic research.”

Unsurprisingly, it’s Pollan who best articulates the here and now.

“What excites me is the potential of these medicines to help people for whom we don’t have a lot to offer. Mental-health care worldwide has not been that effective. We still deal with very high rates of mental illness, and that’s all getting worse,” he says. “So the idea that we might have a tool that could help with a whole range of different problems – from addiction and depression to obsession and anxiety – that’s very exciting.”

They will not offer a silver bullet in the fight against mental-health issues – nothing ever has. But by reducing the stigma around psychedelics, there is now increasing evidence that these treatments may offer new hope to those at the very precipice of despair. Seems it might be time to open our minds.

https://www.gq.com.au/fitness/healt...y/news-story/7e842aeeb49933fe41ffac0046d0520a
 
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Albert Hofmann and Stanislav Grof

How psychedelic drugs are changing lives and transforming psychiatry

by Deanne Bender | CBC Radio | Dec 28, 2018

Meet three people whose lives have been transformed by psychedelic drug research

For decades, hallucinogens have been associated with technicolour dance floors, sitar-driven Beatles tunes and the controversial evangelism of Timothy Leary.

But today, drugs like LSD and MDMA are undergoing a radical transformation — from party drug to potentially revolutionary treatment tool.

Around the world, clinical trials are examining psychedelic drug therapy as a possible treatment for everything from PTSD to cigarette addiction.

To date, many of the studies have been preliminary, with small sample sizes.

But experts say MDMA and psilocybin — better known as ecstasy and the key ingredient in magic mushrooms — could be available for prescription use within the next five years.

Earlier this year, Day 6 spoke with the researchers behind the studies — and the patients who say psychedelic therapy has changed their lives.

Here are some of their stories.

The army veteran

On Christmas Eve in 2006, Sergeant Jon Lubecky put a gun to his temple and pulled the trigger.

He was at peace with the decision to end his life. But the bullet never came.

Earlier that year, Lubecky had suffered a traumatic brain injury during a mortar strike on the base where he'd served in Iraq. When he returned to the United States, he was diagnosed with severe post-traumatic stress disorder.

"I'd wake up hearing explosions that weren't there," he recalled.

For eight years, Lubecky struggled with traumatic flashbacks and severe depression. None of the treatments he tried made a meaningful difference.

Then, in 2014, a medical intern handed him a cryptic note that said: "Google MDMA PTSD."

Later that year, with a trained therapist at his side, Lubecky took ecstasy for the first time.

He was one of 24 participants in a small study in Charleston, South Carolina using MDMA-assisted psychotherapy to treat severe, treatment-resistant PTSD.

Years later, he says his PTSD symptoms are largely gone.

"It was a miracle that changed my life."

He wasn't alone: 67 per cent of the study's participants were still PTSD-free one year after their treatment.

In 2018, researchers launched a Phase 3 clinical trial looking at MDMA-assisted psychotherapy in collaboration with Health Canada and the FDA.

If their findings line up with earlier studies, they say MDMA could be a legal prescription drug by 2021.

Other psychedelic compounds could be on a similar path — and mental health advocates aren't the only ones taking note.

George Goldsmith first became aware of the renaissance in psychedelic drug research when his son, who suffered from treatment-resistant depression, was treated with ketamine.

In 2016, Goldsmith became the co-founder of Compass Pathways, one of the first for-profit companies seeking capitalize on psychedelic drug research.

He believes psilocybin, the key ingredient in magic mushrooms, could be a legal prescription drug as early as 2022.

Lubecky believes psychedelic therapy has the potential to eradicate PTSD.

"I have really high hopes."

The medical student

Octavian Mihai was officially declared cancer-free in 2013, but his mental health was steadily getting worse.

At 21, the NYU student was terrified that the cancer might come back. After his treatment ended, those worries spiralled out of control.

"It was just crippling anxiety," he said.

Deeply concerned for his mental health, his doctor put Mihai in touch with a team of researchers at NYU who were studying psychedelic therapy as a possible treatment for anxiety in cancer patients.

Later that year, after weeks of careful preparation, Mihai put on a pair of noise-cancelling headphones and ingested a little white capsule of psilocybin.

He spent the next eight hours on an intense psychedelic journey — one that lifted him outside himself, and ultimately helped him overcome his fear of dying.

"I lost complete sensation of my body, and I just lifted myself to a different plane," he said.

Researchers are still working to determine exactly how psychedelic drugs affect the mind.

According to psychologist Alison Gopnik, psilocybin decreases activity in the brain's "default mode network," which is responsible for generating our sense of self.

Gopnik believes the disruption of that network could increase our flexibility in thought, paving the way for new perspectives.

"What psilocybin seems to do is to push an adult brain back more to that state of exploration and learning," she said.

Five years later, Mihai's cancer-related anxiety has never returned.

"I've lived every day not worried about it."

The lifelong smoker

For nearly 40 years, cigarettes were Alice O'Donnell's constant companion.

"Cigarettes were the crutch," she said. "I finally reached the point that I could not go to sleep at night unless I knew I had at least a half a pack of cigarettes available for morning."

Over the years, she tried unsuccessfully to quit many times. But after a Pilates class left her on the verge of collapse, she decided to ditch the habit for good.

Shortly thereafter, in 2012, she enrolled in a Johns Hopkins University study using psilocybin as a tool for smoking cessation.

The drug induced powerful hallucinations, including a disturbing vision of her own damaged lungs.

Alice never smoked again, but she says the drugs had other benefits as well: "Just the whole expansion of my thought processes; realizing how great the universe is out there," she said.

Researcher Matthew Johnson, who helped facilitate Alice's psychedelic therapy, likened the experience to a "crash course in meditation."

Those apparent benefits lead some academics, including Jules Evans, a philosopher who studies "ecstatic experiences," to speculate that psychedelic drug therapy could eventually become a mainstream wellness practice.

Is psychedelic drug therapy on track to become as ubiquitous as meditation?

Evans believes many people could benefit from access to the drugs. But he also warns that experiences like Alice's are far from inevitable.

Rather, they tend to be shaped by the expectations of researchers and therapists who serve as guides.

"The music that they play is going to affect your trip; the instructions that you get on the trip are going to guide it," Evans said. "The way that your therapist helps you to make sense of your experience will shape it as well."

Moreover, for people who are predisposed to conditions like schizophrenia, the drugs can have negative long-term consequences.

Nonetheless, O'Donnell hopes clinical psychedelic therapy will become more widely available in the future.

"I definitely think others could benefit from it."

https://www.cbc.ca/radio/day6/the-b...g-lives-and-transforming-psychiatry-1.4955762
 
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Ketamine and Quantum Psychiatry


Karl Jansen, Stanislav Grof, Rick Strassman, Sylvia Thyssen, Lester Grinspoon, James B. Bakalar, Dale Pendell, Jon Atkinson, Louise Theodosiou, Kevin Brunelle, Dave Cunliffe

The word 'psychedelic' was invented by an English psychiatrist (Humphry Osmond) and means 'mind-revealing'. A psychedelic drug may tell us more about how the mind constructs reality, personality and a sense of meaning and sacredness. It is sometimes said that ketamine is not a psychedelic drug because it has anaesthetic properties not seen with LSD, DMT, psilocybin and mescaline. Nevertheless, it can access all of the realms of consciousness mapped out by psychiatrist Stanislav Grof on the basis of LSD research. Ketamine is mentioned in (for example) Psychedelics Encyclopedia, Psychedelic Drugs Reconsidered and The Essential Psychedelic Guide.

Ketamine is relatively safe when used in hospitals. There is a wide margin between the top end of the medical range and a lethal dose. Psychedelic doses are usually only 10-25% of surgical doses, given by the same route for the same person. At these levels, it behaves more like a stimulant than a sedative and does not usually suppress the breathing or heart rate, although exceptions do occur. The higher brain is switched on rather than shut down. This state is different from being unconscious, where the light-bulb is turned off and if the person goes too far they may stop breathing. There are cases of accidental injections with 10 times the amount required for surgery, with no obvious, lasting ill-effects. When ketamine is taken outside a medical setting, the main dangers arise from the physical incapacity it produces.

Dose, how the drug is taken, set and setting have an influence on the experience. 'Set' refers to the personality, past experiences, mood, motivations, intelligence, imagination, attitudes, what is going on in his or her life and the expectations of the person. Expectations are affected by what people hear and read about the drug. 'Setting' refers to the conditions of use, including the physical, social and emotional environment and the other people present. Empathy with the person giving the drug is a very important factor, even with an anaesthetic.

Near-Death and Near-Birth Experiences

A 'near-death experience' (NDE) is a report of leaving the physical body, and sometimes going through a tunnel towards 'the light'. Ketamine can reproduce all aspects of the NDE, including the conviction of being dead, having a telepathic communion with God, seeing visions, out-of-body trips, mystical states, entering other realities, re-experiencing old memories, and a life review which may have therapeutic value Most NDE's occur in people who are not physically near death.

An NDE can be therapeutic. After-effects can include an enhanced joy in living, reduced fear of death, increased concern for others, reduced levels of anxiety and neurosis, reduced addiction, improved health and a resolution of various symptoms. Positive changes can also follow ketamine -induced NDE's (K-trips) which occur within a therapeutic alliance, in an appropriate set and setting. This is called death-rebirth psychotherapy.

Where do these experiences originate? I have written at some length about the physical basis for them in the past. In this article I will consider more speculative suggestions that the brain can act as a transceiver, converting energy fields beyond the brain into features of the mind, as a television converts waves in the air into sound and vision. Advances in quantum physics suggest that certain drugs, and the conditions which produce NDE's, may 're-tune' the brain to provide access to certain fields and 'broadcasts' which are usually inaccessible. This re-tuning is said to open doors to realms which are always there, rather than actually producing those realms, just as the broadcast of one channel continues when we change channels.

The Quantum Mind

Some people believe that ketamine is a mental modem which can potentially connect the mind to 'everything else', allowing a peek behind the curtain at the inner workings of this and other realities. In the old Newtonian universe, the mechanical view declared that all possible forms of energy and fields had already been discovered; that the ordinary, everyday perception of space, time and matter and energy was the only scientifically correct reality; that all people were separate from each other and the rest of the universe; and that consciousness could not exist without a living brain.

Some of these declarations can be reassessed in the light of new discoveries in physics. A subatomic particle can be in many different places at once. When a photon changes in one place and time, it's 'linked photon' changes simultaneously, even if it is on the other side of the universe. It's as if there was no space between them at all. This means that some physical boundaries could be arbitrary. A messy explanation for this is tachyon theory, faster-than-light particles which carry messages between the photons. Bell's theorem is more attractive. This involves a hyperspace where all realities exist at a single point, so no messages are required.

If entry can be gained to the quantum realm, awareness (the 'disembodied eye') might travel through different realities without the body itself going anywhere.

It was like a cosmic assembly line that was constantly churning out the alternate universes that some physicists theorise about in which every conceivable possibility becomes an actual reality. I even had brief flashes in which I experienced some of these alternate realities as they sprouted forth out of this cosmic womb...quick glimpses into what felt like other incarnations, other lives I could have led, darting journeys through seas of pure information. (Trey Turner, 100 mg ketamine i.m.)

A person is not a photon, and it is a real quantum leap to go from the subatomic world to human events. Nevertheless, to improve our understanding of psychedelic experience we may need to reconsider some of the material which has been dismissed as hallucinations, psychosis, suggestibility, stupidity and fraud. Hallucination is only another descriptive term - it doesn't really explain anything. 'Quantum' based explanations for certain mental states have started to appear, and we should be wary of dismissing these new theories out of hand. Some of the most significant advances were opposed by the most renowned scientists of the day. Einstein himself opposed quantum physics, declaring that God did not play at dice. Einstein described this physics as 'absurd, bizarre, mind-boggling, incredible, beyond belief...' and 'the system of delusions of an exceedingly intelligent paranoiac, concocted of incoherent elements of thought'. However, Einstein was wrong. The 'system of delusions' worked very well, and its 'psychotic' advocates won many Nobel prizes. Subatomic particles could indeed behave as if time and space were non-existent.

It was next observed that there are similarities between quantum processes and human thought processes. Leading physicists suggested that consciousness may involve quantum events, with profound implications for understanding certain altered states of being. Professor Stephen Hawking, who sits in Newton's former chair at Cambridge, believes that the universe has no boundaries in space or time, and is made up of super-strings which vibrate in 'extra dimensions', balancing vibrations in the usual dimensions: positive and negative energies cancelling each other to produce the our universe, based on a 'new' kind of symmetry called 'super symmetry'. The latest atom smasher may provide evidence of this super symmetry, producing the world's most expensive Yin-Yang symbol. Has the division between physicists and psychedelic mystics become one of whether instruments or the mind itself is used to make the same observations about 'the ground of being'? The language of LSD trips can resemble the language of the older quantum physics, involving white light and dancing particles, but new reports in physics journals use terms which are much closer to 'the language of ketamine'. Super-string theory is being supplanted by the discovery of whole groups of extended objects called p-branes . These may be viewed as types of membranes, with a string being a one-brane as its only dimension is length. There are other types of 'branes' with far more dimensions. Becoming an across-the-universe membrane is a typical ketamine effect. Before p-brane theory was widely known, ketamine and isolation tank explorer John Lilly MD wrote:

At the highest level of satori from which people return, the point of consciousness becomes a surface or a solid which extends throughout the whole known universe. This used to be called fusion with the Universal Mind or God. In more modern terms you have done a mathematical transformation in which your centre of consciousness has ceased to be a travelling point and has become a surface or solid of consciousness...It was in this state that I experienced 'myself' as melded and intertwined with hundreds of billions of other beings in a thin sheet of consciousness that was distributed around the galaxy. A 'membrain.

Thus transpersonal events may be possible within the new physics, if subatomic events are involved in consciousness. Ketamine may be a drug which 're-tunes' the brain to allow awareness to enter the quantum sea. If this is indeed the case, then we may have to regard some of the reports of eternity, infinity, multiple universes and linkage with other beings as phenomena demanding a more sophisticated explanation than a brief dismissal as 'hallucinations and mental illness' requiring no further consideration.

Ketamine Psychedelic Therapy (KPT)

Over the past 15 years, ketamine has been given to over 1,000 patients in St. Petersburg as an aid to psychotherapy, mainly to assist in the treatment of alcoholism in well-planned trials with proper clinical control groups. The scientific rigour of these studies is impressive. Long-term follow-up of patients has been very encouraging, and the treatment has been extended to heroin addicts and some forms of neurosis. Not a single patient has had complications such as prolonged psychosis, flashbacks or non-prescribed use of ketamine. This work has been carried out by psychiatrist Dr. Evgeny Krupitsky and his team. Evgeny is Chief of the Laboratory, and was recently awarded an honorary Doctor of Science. He spent a year with the ketamine research team at Yale, sponsored by the conservative National Institute of Drug Abuse.

Sessions are supervised by two physicians, a psychotherapist and an anesthetist. A return to normal usually began after 45 minutes to an hour, with a recovery period of 1- 2 hours.

In addition to very good rates of sobriety at one and two year follow-up compared to the control group, on tests of personality change there are significant improvements in many scales including depression, anxiety and ego strength. People become more confident about their own ability to control their lives and to accept responsibility. Non-verbal emotional attitudes are brought to the surface and made known, resulting in less conflict between verbal /conscious and non-verbal/unconscious attitudes involving alcohol, the personality and other people.

There was also a shift in values towards creativity, self improvement, spiritual contentment, social recognition, achievement of life goals, independence, and improvement of family and social life. Life became more meaningful, and the ability to live according to that meaning increased. KPT can reconnect the ego with denied parts of the self. It can also lead to a perception of reconnection with 'wider fields' such as the family, community, planet and universe in general - a form of spiritual experience. Changes in spirituality were assessed using scales designed to measure spiritual change in the Alcoholics Anonymous approach, and the Life Changes Inventory developed to assess the outcome of NDE's.

We try to assist in the patient's psychological integration of the spiritual transformation which can result from the psychedelic experience. The uniquely profound and powerful experience often helps them to generate new insights that enable them to integrate new, often unexpected meanings, values and attitudes about the self and the world. (Krupitsky and Grinenko, 1997)

'I saw the Light' conversions have long been linked with spontaneous recovery from addiction and criminality. All of the 12-step programs, such as Alcoholics Anonymous, have a spiritual orientation and require acceptance of the guidance of a 'higher power'. This may be seen as part of the psyche or a separate entity, depending on personal belief.

Death-Rebirth Psychotherapy

An NDE can be a pivotal turning point, encouraging significant and positive life changes. People who attempt suicide have a subsequent risk of making further attempts which is at least 50 -100 times greater than the normal population. In contrast, suicide attempts which result in NDE's are followed by a reduced risk of further attempts, despite an increased belief in an after-life. Of those who survived a jump from the Golden Gate bridge and had an NDE, none went on to completed suicide, and all were united in their support for a barrier to prevent further attempts. These findings suggested that the artificial induction of NDE's by relatively safe means, within a therapeutic alliance in an appropriate set and setting, might have positive benefits in some people.

The Back Pages

Throughout human history, altered states of being have played a part in healing. The roles of priest and doctor came together in one person (e.g. shaman, 'witch-doctor' etc.) who entered 'mental realms', perhaps aided by psychoactive plants, to speak with spirits for the good of the people. Sometimes, they took the ill person into these realms with them.

The belief that inducing such states for therapeutic purposes was a mis-guided idea of the 1960's, now abandoned due to lack of efficacy and unacceptable risks, is incorrect. This was not a minor curiosity of the lunatic fringe. From 1950 to 1970, more than 1,000 peer-reviewed publications appeared on the clinical use of LSD, in over 40,000 patients. The aims included strengthening the therapeutic alliance, diagnosis, gaining access to memories, and improving insight and the relief of symptoms. Conditions treated included anti-social behaviour, alcoholism, obsessional neurosis, and the psychological problems of the dying. Many of the professionals involved were not at all radical, or even liberal, in outlook. This large enterprise came to a sudden halt when LSD was placed in class A/schedule 1.

New treatments have frequently been greeted with widespread and inappropriate use, and extravagant claims. They then sink to their proper place in the medical cupboard. In some cases, this can be affected by political, social and ideological factors. The only psychedelic drug which can be used in medicine is ketamine, where it may be used to prevent pain in the body but is not licensed for the treatment of pain in the mind.

In the normal course of events, treatment involving psychedelic drugs would have eventually found its proper place, after the extravagant claims phase had passed, with the usual list of possible adverse effects, indications and contra-indications, cautions and precautions, advocates and opponents -as exist for all forms of treatment. Psychedelic drugs, however, became caught up in an intense ideological battle. The result was that not only did all therapeutic use come to an abrupt halt after 20 years, but almost all research projects were also suppressed. This did not happen because a serious new side-effect emerged, or because there was absolutely no evidence of efficacy. The complete ban on psychedelic drug research appears to have arisen from issues which are largely ideological. Ketamine provides an example of the processes involved. It has been given to millions of patients, and there are numerous reviews affirming its safety (when used in a controlled medical context) and value. In most countries it is not even a controlled drug. Nevertheless, if a research proposal is made involving 10% of the normal anaesthetic dose, to be given to healthy informed volunteers, and the word 'psychedelic' appears anywhere in the proposal, there is immediate and grave concern amongst ethical committees where anaesthetic trials may proceed with relative ease. It is difficult to explain this anomaly using scientific and health concerns. These anomalies have led to suggestions that this era has a taboo against having certain aspects of the mind revealed. Ketamine may provide an example of this taboo: a relatively safe medicine which is suddenly seen as unsafe because it is described as a psychedelic drug rather than a dissociative anesthetic. Nevertheless, research with this substance is proceeding in several countries and may eventually lead to the development of a 'quantum psychiatry', just as Freudian psychiatry , which saw psychic energy as a head of steam in the mind, took its cue from Newton's mechanical outlook 100 years earlier.

https://www.erowid.org/chemicals/ketamine/ketamine_journal5.shtml
 
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Psychedelics: A paradigm shift for psychiatry*

by Amanda Feilding | Beckley Foundation | 22 May 2020

In the UK, 1 in 4 people are affected by mental illness. 1 in 3 teenage girls suffer from an anxiety or depressive disorder, and suicide is the leading cause of death in the young. Nearly 50% of the population will develop a mental health disorder at some point during their lifetime, and the World Health Organization has declared that depression is the leading cause of disability. Mental illness costs the UK economy an estimated 100 billion pounds every year.

The number of antidepressants prescribed in England has more than doubled in the last decade, with the most common treatment being SSRIs. Of the 30% of patients who receive no benefit from current pharmacological treatment, up to 15% will go on to kill themselves.

Against this backdrop, it is surprising that no major breakthrough in drug development for depression and other psychological disorders has happened in the past three decades, since the discovery of SSRIs.

In the last 20 years, research from the Beckley Foundation and others has found that psychedelics such as psilocybin can produce dramatically higher rates of efficacy than any other available treatments. As tools to aid psychotherapy, they work immediately, after a single or a few doses, with benefits lasting weeks, months or years, with no negative or long-term side-effects.

As part of the Beckley/Imperial Psychedelic Research Program, in 2016 we investigated the effects of psilocybin-assisted psychotherapy in treatment-resistant depression. The patients we recruited had suffered from moderate-to-severe depression for an average of eighteen years, and had received no relief from conventional medicines or psychotherapy. A first session with a small dose of psilocybin confirmed that the compound was well-tolerated by each patient. In another session shortly after, a larger dose – with more intensely felt psychoactive effects – was given. Two clinicians stayed with the patients in a softly lit, comfortable room, allowing the patients to experience a mostly uninterrupted journey, with occasional ‘check-ins’ to make sure they were doing well.

A week after the second session, all patients showed a reduction in depression severity, with 67% of them meeting criteria for complete remission. These impressive results were robust over time: at three-months 42% of all patients remained depression-free, and more than half displayed significant improvements in depression severity relative to their pre-psilocybin scores.

Since the 1960’s I have been greatly interested in the mechanisms underlying the changing states of consciousness brought about by psychedelics. Our fMRI studies with psilocybin and LSD investigated the changes in blood supply within the brain as well as neuronal connectivity. In doing so we have begun to reveal the mechanisms underlying the significant promise of these compounds as tools to aid psychotherapy.

One of the most striking effects we observed was a decrease in blood supply and thus activity within the Default-Mode Network (the DMN), a collection of widespread brain regions that work together to coordinate the activity of diverse areas of the brain, in doing so controlling our conscious experience and maintaining our sense of self. When the DMN disintegrates under LSD or psilocybin, the inhibitory control it normally exerts over the other areas of the brain weakens, allowing for a dramatic increase in global connectivity, allowing regions to communicate with distant partners with which they typically do not talk. As well as producing the subjective experience of ‘ego dissolution’, this process leads to the emergence of a more complex, less predictable, and more flexible state of consciousness. In this state, long-lasting changes can take place, repressed memories can be accessed, and the maladaptive thought processes of depression and other psychological disorders can be reset, like a computer being rebooted.

The potential for psychedelic-assisted psychotherapy does not stop at treating depression. Dysfunction of the DMN is implicated in a whole host of other mental health conditions, including addiction, obsessive-compulsive disorder, anxiety, and PTSD, among others. What characterizes them all is an excessive pattern of thought or behavior becoming rigid and entrenched, almost impossible to break out of despite an awareness of their destructiveness. An experience of a ‘peak state’, brought about by a psychedelic, provides a chance for an individual to see the inner self and the outer world afresh, affording an opportunity to begin anew.

Although a deeper understanding of brain mechanisms underlying this treatment has only been made possible by modern neuroimaging techniques, the potential for psychedelics to heal in this way is not a recent discovery. LSD was considered a wonder-drug when it first appeared in the 1950’s. Hundreds of published papers and thousands of patient reports testified to its promise for new treatments for a wide range of illnesses. A recent meta-analysis of the best-controlled studies conducted in the 1960’s using LSD for alcohol use disorder – a condition which, to this day, has notoriously poor treatment outcomes– found a single session to be more successful in treating alcohol dependence than daily doses of acamprosate or naltrexone, our current go-to pharmacological interventions. Bill Wilson, the founder of Alcoholics Anonymous, wanted to include LSD-therapy in the treatment program for alcohol dependence, understanding that the subjective effects of LSD – which we now know to be caused by the disintegration of the DNM and an increased plasticity of the brain state– can help to achieve a change in perspective that allow recovery to begin.

Psychedelic-assisted psychotherapy can create a truly revolutionary paradigm-shift in psychiatry. This is not some far-off medical advance visible on the horizon, awaiting some technological breakthrough before becoming feasible. Psychedelic-assisted therapy could be made available in clinics right away, were it not for repressive regulation. But the psychedelics remain among the most heavily restricted compounds in the world: in the UK, they are Schedule 1 drugs under the Misuse of Drugs Act and Misuse of Drugs Regulations. Both classifications categorize the psychedelics as having no medical use, as well as being extremely dangerous.

It is now clear that both of these accusations are demonstrably untrue. The foregoing examples provide a brief introduction to their therapeutic potential. Our studies have found that, when administered by skillful clinicians in controlled environments, psychedelics present no significant risk and are not addictive. Meanwhile, recent population studies –analyzing information from more than 120,000 people – have found no link between psychedelic use and mental health problems.

Modern psychiatry is failing huge numbers of people. The research undertaken in the last decade has suggested many areas where psychedelics could be invaluable for alleviating the suffering of mental health issues. And yet, further research is constantly obstructed by legislation that makes it prohibitively expensive, extremely time-consuming, or impossible for researchers to access the materials we need at affordable prices.

The hesitance of some towards reforming these regulations is easily enough understood. An entire generation has been told that psychedelics are harmful to health, that they are toxic and dangerous. But a more informed attitude is possible – indeed it is already endorsed by many, if not most. The potentially deadly opiate family contains morphine, a useful painkiller.

Amphetamines can be prescribed as a treatment for ADHD, or become a drug of potential abuse when taken recreationally as a stimulant. With the appropriate clinical oversight, a compound’s therapeutic benefits can vastly outweigh its risks. By moving psychedelics from Schedule 1 to Schedule 2, where morphine and amphetamines currently sit, doctors can prescribe them to those in need, and further research can be carried out much more easily.

Our approach to these drugs has so far been characterized by patterns of thought and behavior that have become rigid and entrenched, hard to break out of despite an awareness of their destructiveness. Let us put health, and the reduction of suffering ahead of political expediency and rigid-thinking: the time to act is now.

*From the article here :
http://beckleyfoundation.org/2018/0...psychedelics-a-paradigm-shift-for-psychiatry/
 
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Large Hadron Collider (LHC) at CERN

A Brief History of Psychedelic Psychiatry

by Mo Costandi | The Guardian | 2 Sep 2014

In the 1950s a group of pioneering psychiatrists showed that psychedelic drugs had therapeutic potential, but the research was halted as part of the backlash against the hippy counterculture.

On 5th May, 1953, the novelist Aldous Huxley dissolved four-tenths of a gram of mescaline in a glass of water, drank it, then sat back and waited for the drug to take effect. Huxley took the drug in his California home under the direct supervision of psychiatrist Humphry Osmond, to whom Huxley had volunteered himself as “a willing and eager guinea pig.”

Osmond was one of a small group of psychiatrists who pioneered the use of LSD as a treatment for alcoholism and various mental disorders in the early 1950s. He coined the term psychedelic, meaning ‘mind manifesting’ and although his research into the therapeutic potential of LSD produced promising initial results, it was halted during the 1960s for social and political reasons.

Born in Surrey in 1917, Osmond studied medicine at Guy’s Hospital, London. He served in the navy as a ship’s psychiatrist during World War II, and afterwards worked in the psychiatric unit at St. George’s Hospital, London, where he became a senior registrar. While at St. George’s, Osmond and his colleague John Smythies learned about Albert Hoffman’s discovery of LSD at the Sandoz Pharmaceutical Company in Bazel, Switzerland.

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Osmond and Smythies started their own investigation into the properties of psychedelics and observed that mescaline produced effects similar to the symptoms of schizophrenia, and that its chemical structure was very similar to that of the hormone and neurotransmitter adrenaline. This led them to postulate that schizophrenia was caused by a chemical imbalance in the brain, but these ideas were not favourably received by their colleagues.

In 1951 Osmond took a post as deputy director of psychiatry at the Weyburn Mental Hospital in Saskatchewan, Canada and moved there with his family. Within a year, he began collaborating on experiments using LSD with Abram Hoffer. Osmond tried LSD himself and concluded that the drug could produce profound changes in consciousness. Osmond and Hoffer also recruited volunteers to take LSD and theorised that the drug was capable of inducing a new level of self-awareness which may have enormous therapeutic potential.

In 1953, they began giving LSD to their patients, starting with some of those diagnosed with alcoholism. Their first study involved two alcoholic patients, each of whom was given a single 200-microgram dose of the drug. One of them stopped drinking immediately after the experiment, whereas the other stopped 6 months later.

Several years later, a colleague named Colin Smith treated another 24 patients with LSD, and subsequently reported that 12 of them were either “improved” or “well improved” as a result of the treatment. “The impression was gained that the drugs are a useful adjunct to psychotherapy,” Smith wrote in a 1958 paper describing the study. “The results appear sufficiently encouraging to merit more extensive, and preferably controlled, trials.”

Osmond and Hoffer were encouraged, and continued to administer the drug to alcoholics. By the end of the 1960s, they had treated approximately 2,000 patients. They claimed that the Saskatchewan trials consistently produced the same results – their studies seemed to show that a single, large dose of LSD could be an effective treatment for alcoholism, and reported that between 40 and 45% of their patients given the drug had not experienced a relapse after a year.

At around the same time, another psychiatrist was carrying out similar experiments in the U.K. Ronald Sandison was born in Shetland and won a scholarship to study medicine at King’s College Hospital. In 1951, he accepted a consultant’s post at Powick Hospital near Worcester, but upon taking the position found the establishment to be overcrowded and decrepit, with patients being subjected to electroshock treatment and lobotomies.

Sandison introduced the use of psychotherapy, and other forms of therapy involving art and music. In 1952, he visited Switzerland where he also met Albert Hoffman, and was introduced to the idea of using LSD in the clinic. He returned to the U.K. with 100 vials of the drug – which Sandoz had by then named ‘Delysid’ – and, after discussing the matter with his colleagues, began treating patients with it (in addition to psychotherapy) towards the end of 1952.

Sandison and his colleagues obtained results similar to those of the Saskatchewan trials. In 1954 they reported that “as a result of LSD therapy, 14 patients recovered (av. of 10 treatments), 1 was greatly improved (3 treatments), 6 were moderately improved (av. of 2 treatments) and 2 not improved (av. of 5 treatments).”

These results drew great interest from the international mass media, and as a result, Sandison opened the world’s first purpose-built LSD therapy clinic the following year. The unit, located on the grounds of Powick Hospital, accommodated up to 5 patients who could receive LSD therapy simultaneously. Each was given their own room, equipped with a chair, sofa, and record player. Patients also came together to discuss their experiences in daily group sessions. (This backfired later, however: In 2002, the National Health Service agreed to pay a total of 195,000 pounds sterling in an out-of-court settlement to 43 of Sandison’s former patients.)

Meanwhile in Canada Osmond’s form of LSD therapy was endorsed by the co-founder of Alcoholics Anonymous and the director of Saskatchewan’s Bureau on Alcoholism. LSD therapy peaked in the late 1950s and early 1960s, and was widely considered to be “the next big thing” in psychiatry, which could supersede electroconvulsive therapy and psychosurgery. At one point, it was popular among Hollywood superstars such as Cary Grant.

Two forms of LSD therapy became popular. One, called psychedelic therapy, was based on Osmond and Hoffer’s work, and involved a single large dose of LSD alongside psychotherapy. Osmond and Hoffer believed that hallucinogens are beneficial therapeutically because of their ability to make patients view their condition from a fresh perspective.

The other, called psycholytic therapy, was based on Sandison’s regime of several smaller doses, increasing in size, as a adjunct to psychoanalysis. Sandison’s clinical observations led him to believe that LSD can aid psychotherapy by inducing dream-like hallucinations that reflected the patient’s unconscious mind and enabling them to relive long-lost memories.

Between the years of 1950 and 1965, some 40,000 patients had been prescribed one form of LSD therapy or another as treatment for neurosis, schizophrenia, and psychopathy. It was even prescribed to children with autism. Research into the potential therapeutic effects of LSD and other hallucinogens had produced over 1,000 scientific papers and six international conferences. But many of these early studies weren’t particularly robust, lacking control groups, for example, and likely suffered from what researchers call publication bias, whereby negative data are excluded from the final analyses.

Even so, the preliminary findings seemed to warrant further research into the therapeutic benefits of hallucinogenic drugs. The research soon came to an abrupt halt, however, mostly for political reasons. In 1962, the U.S. Congress passed new drug safety regulations, and the Food and Drug Administration designated LSD as an experimental drug and began to clamp down on research into its effects. The following year, LSD hit the streets in the form of liquid soaked onto sugar cubes; its popularity grew quickly and the hippy counterculture was in full swing by the summer of 1967.

During this period, LSD increasingly came to be viewed as a drug of abuse. It also became closely associated with student riots anti-war demonstrations, and thus was outlawed by the U.S. federal government in 1968. Osmond and Hoffer responded to this new legislation by commenting that “it seems apt that there is now an outburst of resentment against some chemicals which can rapidly throw a man either into heaven or hell.” They also criticised the legislation, comparing it to the Victorian reaction to anaesthetics.

The 1990s saw a renewed interest in the neurobiological effects and therapeutic potential of psychedelic drugs. We now understand how many of them work at the molecular level, and several research groups have been performing brain-scanning experiments to try to learn more about how they exert their effects. A number of clinical trials are also being performed to test the potential benefits of psilocybin, ketamine and MDMA to patients with depression and various other mood disorders. Their use is still severely restricted, however, leading some to criticise drug laws, which they argue are preventing vital research.

Huxley believed that psychedelic drugs produce their characteristic effects by opening a “reducing valve” in the brain that normally limits our perception, and some of the new research seems to confirm this. In 1963, when he was dying of cancer, he famously asked his wife to inject him with LSD on his deathbed. In this, too, it seems that he was prescient: Several small trials suggest that ketamine alleviates depression and anxiety in terminally ill cancer patients and, more recently, the first American study to use LSD in more than 40 years concluded that it, too, reduces anxiety in patients with life-threatening diseases.

https://www.theguardian.com/science/...lic-psychiatry
 
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First International Treatment Center for Psychedelic Psychiatry — in Jamaica*

Psilocybin Alpha | 23 Feb 2021

Aion Therapeutic has announced the opening of the Aion International Center for Psychedelic Psychiatry in Jamaica. The Center will initially specialize in the use of psilocybin for the treatment of addiction (tobacco, alcohol, and other drug misuse), depression and anxiety associated with life-threatening illnesses, treatment-resistant depression, and major depressive disorder (MDD). In addition, the Center will be studying the effectiveness of psilocybin as a new therapy for opioid addiction, Alzheimer’s disease, post-traumatic stress disorder (PTSD), and anorexia nervosa.

The U.S. Food and Drug Administration (FDA) recently designated psilocybin therapy as a “breakthrough therapy” for the treatment of MDD, saying “MDD is a substantial public health concern, affecting more than 300 million individuals worldwide. Depression is the number one cause of disability, and the relative risk of all-cause mortality for those with depression is 1.7 times greater than the risk for the general public. In the United States, approximately 10% of the adult population has been diagnosed with MDD in the past 12 months, and the yearly economic burden of MDD is estimated to be $210 billion. Across the 36 largest countries in the world, in the absence of scaled-up treatment, it is projected that more than 12 billion days of lost productivity (equivalent to more than 50 million years of work) are attributable to depression and anxiety disorders every year, at an estimated cost of US $925 billion. Assuming the same distribution of costs across lower-income and higher-income countries holds for all other countries (representing 20% of the world’s population), the global cost per year is $1.15 trillion.”

The Medical Director of the Aion International Center for Psychedelic Psychiatry is Winston De La Haye, M.D., M.P.H, D.M., I.C.A.P. Dr. De La Haye stated, “We need all available and effective products for the treatment of patients with mental illness. Psychedelic Psychiatry has the potential to change the lives of millions of patients, reducing their disability and improving their quality of life.” Dr. De La Haye continued, “As a Johns Hopkins Alumnus, it is our intention to follow the best treatment protocols like those being established at Johns Hopkins Center for Psychedelic and Consciousness Research.”

Aion International Center for Psychedelic Psychiatry, in addition to treating patients, looks forward to collaborating with The UWI and other Tertiary Institutions in Jamaica in the research and development of cutting edge, effective and safe products for treating patients with mental illness. We also recognize the importance of regulating the Psychedelic Industry and look forward to working closely with the MOHW in Jamaica as they move towards setting up this very important regulatory body.

Dr. Stephen Barnhill, Executive Chairman of Aion Therapeutic, stated, “We’re very excited to be opening the first International Center for Psychedelic Psychiatry in Jamaica. The Center is unique in our ability to treat patients with both psilocybin and medical cannabis combination therapies currently being produced at Aion Therapeutic in conjunction with our licensed medical cannabis partner Apollon Therapeutics Jamaica, Ltd. We are establishing treatment protocols and dosing schedules for international expansion and export when and where the legal use of these products continues to expand globally.” Dr. Barnhill continued, “We are honored to have Dr. Winston De La Haye, with his significant expertise in addiction medicine as the Medical Director for the treatment facility.”

Mr. Graham Simmonds, Executive Vice Chair and CEO of Aion Therapeutic, stated, “This is a very exciting time for the Company as we now embark on treating patients and further advancing our science and research with another excellent doctor added to our team.” He added, “Our team, led by Dr. Barnhill, has been working tirelessly over the past six months in advancing our research, developing our formulations, patent protecting these formulations and preparing an operating plan for treating patients with additional medical conditions including cancer, inflammatory conditions, viral disorders and obesity. We will have updates with further details on our approach to expanding our treatment markets and managing our intellectual property portfolio released shortly. I commend them for this important milestone and we look forward to seeing further advancements from this world-class team we now have in place.”

The offices of Aion International Center for Psychedelic Psychiatry will soon be opened for seeing both Jamaican and international patients. In addition, we are planning a grand opening celebration in the very near future. The grand opening date will be based on the lifting of the COVID-19 restrictions.

*From the article here :
 
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Rethinking serotonin could lead to a shift in psychiatric care

Imperial College London | Sep 4, 2017

A better understanding of how a key chemical messenger acts in the brain could lead to a radical shift in psychiatric care, according to a new research paper.

Serotonin is a neurotransmitter which helps brain cells communicate with one another, playing important roles in stabilising mood and regulating stress.

Despite its importance, current models to explain serotonin's function in the brain remain incomplete.

Now, in a review paper published this month in the Journal of Psychopharmacology, researchers from Imperial College London suggest that serotonin pathways are more nuanced than previously thought.

They argue that the existing view should be updated to incorporate a 'two-pronged' model of how serotonin acts.

The researchers believe their updated model could have implications for treating recalcitrant mental health conditions, including depression, obsessive compulsive disorder and addiction, and could exploit the therapeutic potential of psychedelic drugs.

In the brain, serotonin acts via a number of sites called 'receptors' and serotonin has at least 14 of these. Brain drugs such antidepressants, antipsychotics and psychedelics are known to interact with serotonin receptors and two of these are thought to be particularly important -- the so-called serotonin 1A and 2A receptors.

For patients with depression, commonly prescribed drugs called SSRIs (Selective Serotonin Reuptake Inhibitors) can help to relieve symptoms by boosting levels of serotonin in the brain. Evidence suggests an important part of how they work is to increase activity at the serotonin 1A receptor, which reduces brain activity in important stress circuitry, thereby helping a person cope better.

In contrast, psychedelic compounds such as LSD and psilocybin (the psychoactive component of magic mushrooms), are thought to act primarily on the serotonin 2A receptor. Accumulating evidence suggests that psychedelics with psychotherapy can be an effective treatment for certain mental illnesses and, with a focus on the 2A receptor, the authors' paper attempts to explain why.

Writing in the review paper, the researchers say that while the traditional view of developing psychiatric treatments has been focused on promoting 1A activity and often blocking the 2A, the therapeutic importance of activating the 2A pathway -- the mechanism by which psychedelics have their effect -- has been largely overlooked.

"We may have got it wrong in the past," said Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial and lead author on the paper. "Activating serotonin 2A receptors may be a good thing, as it makes individuals very sensitive to context and to their environment. Crucially, if that is made therapeutic, then the combination can be very effective. This is how psychedelics work -- they make people sensitive to context and 'open' to change via activating the 2A receptor."

According to the researchers, the 1A and 2A pathways form part of a two-pronged approach which may have evolved to help us adapt to adversity. By triggering the 1A pathway, serotonin can make situations less stressful, helping us to become more resilient. However, they argue that this approach may not always be enough, and that in extreme crises, the 2A pathway may kick in to rapidly open a window of plasticity in which fundamental changes in outlook and behaviour can occur.

Growing evidence shows that in conditions such as treatment-resistant depression, obsessive compulsive disorder and addiction, certain brain circuitry may become 'stamped in' and resistant to change. The researchers suggest that in such cases, activating the 2A pathway -- such as through psychedelics -- could potentially offer a way to break the cycle, helping patients to change negative behaviours and thought patterns which have become entrenched.

By enabling the brain to enter into a more adaptive or 'plastic' state and providing patients with a suitably enriched clinical environment when they receive a drug treatment, clinicians could create a window for therapy, effectively making patients more receptive to psychotherapy.

According to the authors, their updated model of how serotonin acts in the brain could lead to a shift in psychiatric care, with the potential to move patients from enduring a condition using current pharmacological treatments, to actively addressing their condition by fundamentally modifying behaviours and thinking.

Professor David Nutt, Director of Neuropsychopharmacology in Imperial's Division of Brain Sciences, explained: "This is an exciting and novel insight into the role of serotonin and its receptors in recovery from depression that I hope may inspire more research into develop 5-HT2A receptor drugs as new treatments."

Dr Carhart-Harris added: "I think our model suggests that you cannot just administer a drug in isolation, at least certainly not psychedelics, and the same may also true for SSRIs. We need to pay more attention to the context in which medications are given. We have to acknowledge the evidence which shows that environment is a critical component of how our biology is expressed."

He added: "In psychiatry, as in science, things are rarely black and white, and part of the approach we're promoting is to have a more sophisticated model of mental healthcare that isn't just a drug or psychotherapy, it's both. I believe this is the future."

'Serotonin and brain function: a tale of two receptors'
by Robin Carhart-Harris and David Nutt is published in the Journal of Psychopharmacology.

https://www.sciencedaily.com/releases/2017/09/170904093724.htm
 
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Neuropsychopharmacologist David Nutt

Scientists zero in on the ideal dose of LSD for psychiatric treatment*

by Eric Dolan | PsyPost | 10 Mar 2021

New research published in Neuropsychopharmacology provides insight into the acute dose dependent effects of LSD. The findings will help in the planning of clinical trials examining the use of the psychedelic drug in patients with psychiatric conditions.

Previous research has provided initial evidence that LSD might be a viable treatment for certain mental disorders when combined with psychotherapy. But these studies have compared a placebo against a single dose of LSD. The authors of the new research set out to scientifically test the effects of LSD across a range of different doses.

“We wanted to generate clinical data on LSD for its later use as medication in patients,” said research Matthias E. Liechti of University Hospital Basel. “The new study provides information on the acute effects of different doses of LSD. This will help to select the right dose for future trials in patient to treat anxiety and depression.”

During six experimental sessions, which occurred under double-blind conditions in a controlled laboratory setting, eight men and eight women received a placebo, four different doses of LSD, and a high dose of LSD combined with ketanserin, a serotonin 2A antagonist that blocks the effects of LSD.

The researchers found that all four doses of LSD — 25 µg, 50 µg, 100 µg, and 200 µg — increased experiences of “oceanic boundlessness” and “visionary restructuralization” compared to placebo. But only the 50, 100, and 200 µg doses of LSD were associated with “ego dissolution,” the experience of losing one’s sense of self.

There was also evidence of a ceiling effect. The positive subjective effects of LSD increased from the lowest dose to 100 µg, but there was no difference in positive drug effects between the 100 and 200 µg doses. Similarly, ratings of oceanic boundlessness and visionary restructuralization also increased from the lowest dose to 100 µg before leveling off.

But the 200 µg dose of LSD produced significantly greater ego dissolution and was the only dose that significantly increased ratings of anxiety compared with placebo.

“Based on the available data, the following dosing terminology may be useful for future LSD research: ‘microdose’ (1–20 µg), ‘minidose’ (21–30 µg), and ‘psychedelic dose’ (>30 µg). Within the psychedelic LSD dose range, good effects likely predominate at doses of 30–100 µg (good-effect dose), whereas ego dissolution and anxiety increase at doses above 100 µg (ego-dissolution dose),” the researchers said.

Some physiological effects were also observed. LSD increased blood pressure at doses of 50 µg and higher, and increased heart rate at 100 and 200 µg.

As expected, administration of ketanserin caused significant reductions in the effects of LSD. “Retrospective reports showed that ketanserin and LSD together were identified correctly by the participants or mistaken as a low dose of LSD but never mistaken for a high dose of LSD,” the researchers explained.

Although the findings help to zero in on the ideal dose to use in psychiatric settings, scientists are likely to further fine tune dosages in additional research.

“Only a limited amount of doses were tested,” Liechti said. “Thus an ideal dose may be between two selected doses. Additionally, the ultimate right doses need to be tested and selected in patients and there are patient characteristics that may result in dose adjustments.”

*From the article here :
 
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Psychedelic Psychiatry | Preparing for novel treatments involving altered states of consciousness

by Brian Holoyda, M.D., M.P.H. | Psychiatry Online | 14 Oct 2020

The past decade has seen a renaissance of research interest into the psychotherapeutic potential of psychedelic compounds. In 2019, Oakland and Denver became the first two jurisdictions in the United States to decriminalize the possession of psychedelic-containing organisms. As research and public policy continue to evolve, it becomes increasingly plausible that psychedelics will become viable treatment options for psychiatric conditions. Psychiatrists should be integral to models of psychedelic prescription and patient management. The risk for adverse psychological and medical effects from psychedelic sessions necessitates psychiatric supervision. The literature on psychedelic-assisted psychotherapy may provide wisdom regarding practical aspects of managing patients’ treatment sessions.

In 1970, the federal government of the United States passed the Controlled Substances Act, which categorized LSD as a Schedule I drug with no recognized medical uses. This decision signaled the cessation of legal research into the use of LSD and other psychedelic compounds for treating psychiatric maladies; up until that time, such research had been thriving. Today, there is renewed research interest in the use of psychedelic substances for the treatment of conditions such as terminal illness–related anxiety and treatment-resistant depression (1). In 2019, two cities in the United States decriminalized the possession of certain psychedelic compounds. In May 2019, the citizens of Denver passed a city ordinance to decriminalize mushrooms containing psilocybin (2). One month later, the city council of Oakland, California, unanimously voted to decriminalize “entheogenic plants” containing psilocybin, mescaline, or DMT (3).

In early 2020, the American Psychiatric Association issued a review of psychedelic therapies indicating that, despite insufficient research to support U.S. Food and Drug Administration (FDA) approval of any psychedelics at that point, continued study of the efficacy of psychedelics for mental disorders was warranted (4). The convergence of new research demonstrating psychotherapeutic benefits from psychedelic compounds and a relaxation of political concern about them suggests that psychedelics may soon become viable medicinal treatments. This Open Forum describes psychiatrists’ necessary role in psychedelic treatment, recommends guidelines for safe distribution and administration, and addresses areas of special concern, including the management of adverse events, informed consent, and the practical aspects of conducting psychedelic-assisted psychotherapy.

Psychiatrists’ role in psychedelic treatment

If psychedelic drugs become approved as treatment modalities, psychiatrists should be responsible for their prescription and the management of patients receiving them First, research on the psychotherapeutic potential of psychedelic compounds has focused on psychiatric conditions, including terminal illness–related anxiety, treatment-resistant depression, and substance use disorders. Because psychiatrists are medical professionals with expertise in the evaluation and management of mental disorders, they are best suited to understand when novel treatments may be appropriate for patients with such conditions. Similarly, psychiatrists are necessary to assess patients for comorbid conditions that may make psychedelic therapy riskier. Concerns about the exacerbation or unmasking of bipolar or psychotic disorders have prompted some researchers to exclude patients with a personal history—or a first- or second-degree relative with a history—of bipolar disorder I, bipolar disorder II, schizophrenia, and other psychotic disorders from participating in studies evaluating the psychotherapeutic benefits of psychedelics (5). Thus, rational prescribing would consider the potential risk factors for individuals having a “challenging experience” (previously referred to as a “bad trip”) or undergoing potentially irreversible psychological harm.

Second, the prescription and administration of psychedelic drugs may cause significant adverse medical effects.

Psychedelic compounds exert their effects through the 5-HT2A receptor, which also mediates smooth muscle contraction, platelet aggregation, and coronary artery spasm. Case reports have documented individuals suffering from rhabdomyolysis with subsequent acute rental failure from the use of psilocybin as well as rhabdomyolysis and limb ischemia from the use of LSD (6). More commonly, however, psychedelic substance use may result in acute or chronic adverse psychological or behavioral effects. In a study of nearly 2,000 individuals with a history of psilocybin use and a prior “challenging experience,” 10 percent reported putting themselves or others at risk of physical harm, 3 percent reported behaving in physically aggressive or violent ways, and 3 percent reported seeking medical attention at a hospital during the experience. Of those whose session occurred over 1 year before the survey, 8 percent sought treatment for enduring psychological symptoms that they attributed to the psilocybin session, which included persistent fear, anxiety, paranoia, and depression (7). Although acute and persistent negative behavioral or psychological outcomes are less common when psychedelic sessions are conducted in a controlled, monitored setting, they nevertheless may occur. Psychiatrists are unique in their ability to assess both medical and psychiatric adverse effects from psychedelic treatments and to manage acutely distressed, agitated, or violent patients with nonpharmacological or pharmacological approaches.

Informed consent

Psychedelic compounds have wide-ranging effects on human consciousness. Although their effects are not entirely dose dependent, low doses tend to cause altered special sense perception and synesthesia. With increasing doses, individuals may experience de-realization, de-personalization, and completely altered consciousness, including loss of time and space perception, transcendent experiences, encounters with otherworldly beings, and the dissolution of one’s sense of self, also known as ego death (8). As described earlier, psychedelics may also cause medical or psychological adverse effects. For these reasons, clinicians utilizing such treatments must engage patients in a thorough informed consent procedure. Patients should have a detailed understanding of their potential reactions to the psychedelic substance. Although it is impossible to know exactly what will occur in a session, psychiatrists should inform patients that they may experience altered sensory perception, impaired logic, and distorted or reduced awareness of time, place, or self. Given psychedelics’ stigmatization as a potential mechanism for “mind control,” resulting largely from governmental experimentation with the compounds, ethical practice will require psychiatrists to be as informative and transparent with patients as possible regarding psychedelic effects before their administration. Prudent practitioners should also review patients’ spiritual or religious backgrounds and beliefs, which may play a role in the content that arises during a psychedelic session.

Because of the potential for psychedelic drugs to disrupt the logic of one’s thought process, patients may lose the capacity to understand information provided to them or to rationally manipulate information to make a medical decision during a session. Therefore, the informed consent procedure conducted before the session must establish a patient’s wishes in certain scenarios that may arise. For example, patients should state whether they will allow physical touch if experiencing emotional distress during a session. Patients should understand that they may become a risk of harm to themselves or others (e.g., because of paranoia, agitation, or efforts to move while disoriented). Patients should know that, in such cases, they may not have the capacity to refuse efforts to reduce the risk of harm (e.g., restraint or, less likely, the application of a sedative). Establishing the patient’s preferences and educating the patient about the risk of adverse events before the session are necessary to reduce the risk of unexpected outcomes and claims of malpractice or battery.

A model for psychedelic administration

If psychedelic drugs become reclassified and approved for the treatment of mental disorders, psychiatrists should encourage the development of a rational model for their dispensation and administration. Although psychedelics have significantly less potential for abuse than other scheduled substances, such as cannabis and opioids (9), their effects are often unpredictable and can severely impair users, especially in nonclinical settings. Therefore, psychedelic administration should be relegated to clinical settings, where patients can be monitored closely to assess their response to the treatment and any adverse effects, as is recommended with intranasal esketamine.

The current models of psychedelic-assisted psychotherapy typically describe a multisession treatment sequence including preparation; drug administration; and “integration,” or therapy that focuses on the experiences that arose while intoxicated with the psychedelic to help clarify their meaning for the individual (10). Beginning with Timothy Leary in the 1960s, researchers have recognized that the psychedelic user’s expectations or previous experiences (or mental “set”) and aspects of the physical environment (or “setting”) could have a significant effect on the psychedelic experience (11). Psychedelic sessions are typically conducted in comfortable rooms with a reclining chair or bed. Music and eyeshades are available, along with sipping water and receptacles in case of nausea and vomiting. Psychiatrists offering psychedelic treatments should adhere to such models for the setting, because standard clinic or laboratory rooms may feel unfamiliar during the session.

High-dose psychedelic sessions may last 6 hours or longer, depending on the substance consumed. A therapist or “guide” is usually present to assist the patient in exploring the experiences that surface during the session as well as to address any discomfort or other adverse events that may arise. Self-styled psychedelic guides have written extensively about their experiences with patients and how to establish a safe, open, trusting environment for patients to be able to benefit from psychedelic journeys (12, 13). Organizations have also developed training sessions and recommendations to assist potential psychedelic-session therapists or guides. For example, the Council on Spiritual Practices established ethical guidelines for spiritual guides who conduct psychedelic sessions (14), and the Zendo Project associated with the MAPS instituted psychedelic peer support training to reduce harm for individuals with challenging experiences while intoxicated (15). Because of time and financial pressures, psychiatrists are unlikely to serve as the therapist or guide for an entire psychedelic session. Other mental health professionals with experience or training in working with patients in altered states of consciousness will likely fill this role under the supervision of psychiatrists. Because of the requirements of psychedelic-assisted therapy described earlier, specialized clinicals will likely be needed for administration. The average community practitioner should be aware of psychedelics as potential treatment options and refer their patients, when appropriate, to a specialty psychedelic clinic.

Conclusions

Although psychedelics will not receive FDA approval until further research occurs, the time is ripe for the medical field (and psychiatry, in particular) to consider how these therapies may best be administered. Psychiatrists should advocate for treatment protocols that emphasize patient autonomy and safety as well as the ability to address any adverse effects that might arise. New models of supervision for those trained to serve as sitters or guides during psychedelic sessions will also be required.

 
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Psychedelics and the Future of Psychiatry

by Reid Robison, MD, MBA | Psychiatric Times | 8 Feb 2022

Over the past several years, we have witnessed a psychedelic renaissance, and a growing body of evidence suggests that several psychedelic compounds hold strong therapeutic potential for a wide array of mental health conditions.

Once dismissed as dangerous and having little therapeutic potential, psychedelic drugs are gaining mainstream acceptance. Research data continue to demonstrate that, on the whole, these medicines are not only safe, but mostly well tolerated. Although more research is needed to better understand safety, especially in the context of at-risk conditions, these favorable safety profiles are enabling deeper exploration of these medicines.

The term psychedelic was coined in the 1950s by psychiatrist Humphry Osmond, MD, and it literally means “mind-manifesting.” This class of drugs produces changes in perception, thought, and mood with minimal disorientation or confusion. Unlike alcohol, benzodiazepines, and barbiturates, psychedelics do not lead to a slowing of cognitive processes or an acceleration of cognition as seen with stimulants.

Several US states and cities are in the process of legalizing or decriminalizing psychedelics like psilocybin, MDMA, LSD, and others for therapeutic or recreational purposes. In 2020, the Oregon Ballot Measure 109 was passed, allowing licensed service providers to administer psilocybin products to individuals 21 years and older and making Oregon the first state to legalize psilocybin. The drug will not be available commercially or for home-based use, as strict regulations are in place to ensure psilocybin will be used only under the supervision of trained facilitators. This was a major milestone in psychedelic medicine, as it opened the door for more widespread access to psilocybin therapy in a safe and legal manner.

The US Food and Drug Administration (FDA) has also shown interest in prioritizing the approval of certain psychedelic drugs. Both psilocybin- assisted psychotherapy for major depressive disorder (MDD) and treatment-resistant depression, as well as MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD), have received the breakthrough therapy designation from the FDA to fast-track the approval process because of the growing clinical evidence demonstrating substantial improvement over currently available therapies.

Safety Issues and Scaling Up

The growing research results continue to confirm that psychedelic medicines are not only safe, but well tolerated by the majority of recipients. A psilocybin study found that cases of mental health complications following a psychedelic are rare, and rarer still with proper screening. Another study examined the classical psychedelics, LSD, psilocybin, and mescaline. It found no evidence of increased rates of mental health problems; in fact, it demonstrated psychedelic use was associated with reduced psychological distress and suicidality. Additionally, results of studies examining psychedelic substance use patterns in humans as well as self-administration in animals suggest that classic psychedelics possess little or no abuse liability and may even be antiaddictive.

Results of other studies suggest psychedelics may have protective effects when it comes to mental illness in general. Pooling more than 190,000 adults, researchers evaluated the relationship of classic psychedelic use and psychological distress and suicidality. They found that lifetime psychedelic use was associated with significantly reduced odds of past-month psychological distress, past-year suicidal thinking, past-year suicidal planning, and past-year suicide attempt.8 This offers new insight into the potential promise of psychedelics in helping to prevent suicide.

More research is still needed to fully understand safety, especially in the context of at-risk conditions and mechanisms of action. However, the favorable safety profiles are opening doors for deeper exploration of these medicines.

MDMA

MDMA-assisted psychotherapy, the psychedelic treatment closest to receiving FDA approval, is currently undergoing phase 3 clinical trials in patients with PTSD.9 The study included 90 patients with severe, chronic PTSD from a variety of different causes (eg, abuse, combat, sexual trauma). It is worth mentioning that this was a treatment-resistant group, meaning patients had suffered with PTSD for an average of 14 years without relief. All participants completed a 12-week treatment program composed of 3 full-day sessions, during which they received either MDMA or a placebo, plus weekly nondrug psychotherapy sessions. No serious adverse effects were detected beyond transient, mild symptoms during drug treatment such as nausea or sweating. No increases in suicide risk or potential for abuse were noted in the MDMA group relative to placebo. Two months after treatment, 67% of the MDMA cohort no longer qualified for PTSD diagnosis, compared with 32% of the placebo group. In addition, 88% of those in the MDMA group experienced a clinically significant reduction in symptoms (Figure 1).

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Figure 1. Effects of MDMA-Assisted Psychotherapy on PTSD

MDMA is unique in its ability to promote acceptance of and empathy for self and others. In addition to elevating oxytocin levels, MDMA stimulates the release of the monoamines serotonin, norepinephrine, and dopamine, resulting in improved mood and increased sociability.10 Brain imaging after administration of MDMA shows there is decreased amygdala activation and reduced fear response, allowing the patient to emotionally engage in therapy without becoming overwhelmed by anxiety or difficult emotions. The combination of medication plus psychotherapy represents a new frontier for the FDA, with unique challenges to be addressed such as therapeutic approaches and therapist training.

Psilocybin

Psilocybin, the main psychoactive component of “magic mushrooms,” is currently in phase 2 clinical trials for MDD. As a classic psychedelic, it is an agonist of serotonergic 5-HT2A receptors in the brain, which are particularly abundant in the cortex and regions associated with cognitive functions and social interactions. Stimulation of this receptor has been directly linked to cognitive flexibility, enhanced imagination, and creative thinking.

In pivotal study results, 71% of individuals with MDD who received 2 doses of psilocybin were treatment responders, and half of the participants entered remission (Figure 2). Some follow-up studies after therapy, although small, have shown lasting benefits.

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Figure 2. Depression Decreases Found After Psilocybin Treatment

Concluding Thoughts

Psychedelic medicine is forging ahead as a promising new treatment paradigm, in which psychedelics, paired with psychotherapy, have the potential to treat various mental health conditions. Preliminary findings show successful results for these treatments, with significant clinical improvements and few—if any—serious adverse effects. The emerging results likely have implications for future psychiatric research, education, and policy—and most importantly, they are poised to offer new therapeutic options and improve the lives of those we serve.

Dr Robison is a board-certified psychiatrist and Chief Medical Officer of Novamind. He is the co-founder of Cedar Psychiatry and serves as the Medical Director for the Center for Change, a leading eating disorders center. Dr Robison previously served as a coordinating investigator for the MAPS-sponsored MDMA-assisted psychotherapy study of eating disorders.

*From the article (including references) here :​
 
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The Resurgence of Psychedelic Psychiatry

On-air radio interview | NPR | April 9, 2021

MADDIE SOFIA, BYLINE: You're listening to SHORT WAVE from NPR.

EMILY KWONG, HOST:

Hi, everybody. Emily Kwong here with NPR science correspondent Jon Hamilton. Hi, Jon.

JON HAMILTON, BYLINE: Hi, Emily.

KWONG: So as NPR's neuroscience reporter, you're always reporting on the most interesting things. So what do you got for us today?

HAMILTON: What I've got for you today is psychedelic drugs - not literally, of course.

KWONG: (Laughter) OK.

HAMILTON: But I want to talk about how these drugs are getting a second look, you know, as a way...

KWONG: Ah.

HAMILTON: ...To treat psychiatric problems like depression, anxiety, substance use disorders, even PTSD. In the past decade, it has become a very hot topic in brain science.

KWONG: Yes. It is a very hot topic. In fact, Jon, our first SHORT WAVE episode was about using psilocybin as a treatment for smoking cessation. So I'm glad you're bringing this topic back to the podcast. What are some of the drugs we'll be talking about today?

HAMILTON: A lot of familiar names. You mentioned psilocybin. There's also ketamine, mescaline, ibogaine, ecstasy, even LSD in some cases.

KWONG: And those are all drugs that can cause hallucinations or out-of-body experiences, right?

HAMILTON: Right. And most of them are not legal.

KWONG: Right. But how do they work for depression and all those other psychiatric conditions?

HAMILTON: So ketamine, for example, is able to help a lot of people with major depression even when nothing else works. About 10 years ago, I was able to talk to one of the first people to take part in a clinical trial of ketamine. His first name is Christopher (ph). He asked me not to use his last name. Christopher had depression that made him suicidal. And before he got ketamine, he had been prescribed just about every drug out there to treat his depression. He told me it started with Prozac and Paxil and went on to...

CHRISTOPHER: Klonopin, Ativan, Valium, Xanax, Remeron, Gabapentin, Buspar. Depakote they had me on for a while.

KWONG: That is a long list. And none of those helped him?

HAMILTON: Either they didn't work or the side effects were so bad, he had to quit taking them. But Christopher was lucky. He managed to get into one of the first studies of ketamine. And now, 15 years later, the FDA has actually approved a version of ketamine for use in people like Christopher.

KWONG: Well, today on the show, we're going to talk about that - the resurgence of psychedelic psychiatry.

HAMILTON: And how these drugs are helping brain scientists understand what causes mental illness and find new ways to treat it.

KWONG: OK, Jon Hamilton, neuroscience correspondent, why are psychedelic drugs getting so much attention now? I mean, they've been around for a long time.

HAMILTON: Yeah, a really long time. I mean, people have been taking plant-based psychedelics like mescaline and psilocybin for thousands of years. And back in the 1950s and early '60s, scientists were actually looking at whether some of these drugs might be useful in psychotherapy or to treat alcoholism or mood disorders like depression. But then there was the Summer of Love - a lot of drug experimentation, a lot of social upheaval. The upshot was that drugs like LSD were labeled a menace to society. And by 1970, they were pretty much outlawed.

KWONG: And did that end all of the research?

HAMILTON: For the most part, yeah, at least until the 1990s. I think the real change, though, came from the ketamine study I mentioned.

KWONG: OK.

HAMILTON: It was published in 2006. And it got people's attention because it was done by a very prominent psychiatrist at the National Institute of Mental Health, Dr. Carlos Zarate. Also, the results were spectacular. The study was of people who all had major depression that had not responded to other treatments. And they got a very low dose of ketamine that wore off in an hour or so. But more than 70% of them got better, and they got better within a few hours of being treated.

KWONG: Wow.

HAMILTON: You remember Christopher from earlier? He told me about getting his first dose at the National Institutes of Health as part of Dr. Zarate's study. It was on a Monday morning, he said. And his mood was really, really dark.

CHRISTOPHER: Monday afternoon, I felt like a completely different person. It was, you know, same-day effects. And, you know, I woke up Tuesday morning, and I said, wow, there's stuff I want to do today. And I woke up Wednesday morning and Thursday morning. And for the first time in I don't even remember, I actually wanted to do things. I wanted to live life.

KWONG: Oh, I'm so glad to hear that. And the effects for Christopher sounded almost immediate. Did those early results hold up for him?

HAMILTON: Well, I checked in with Christopher just a couple of days ago, and now 15 years later, he is still...

KWONG: Still?

HAMILTON: ...Taking ketamine and still doing well.

KWONG: Wow.

HAMILTON: And after the NIH study, lots of scientists began studying ketamine for depression. And they confirmed that it worked for most patients. So pretty soon you had doctors that were opening up these ketamine clinics all around the country where people could go to get infusions of the drug. And these clinics are still giving ketamine to thousands of people with problems like depression, anxiety, PTSD and chronic pain.

KWONG: But ketamine, at least in popular culture, is still kind of known as a party drug, right? It's technically not legal when used that way.

HAMILTON: No, it's not. But it's been approved for use as an anesthetic since 1970. My son actually got it in the emergency room a few years ago. He was 9. He'd broken his arm.

KWONG: Oh.

HAMILTON: And it was the safest way to anesthetize him while they set the bone.

KWONG: OK.

HAMILTON: So ketamine is out there, and doctors can legally prescribe it for purposes other than anesthesia if they think it's in the patient's best interest. And just to finish the story about ketamine for depression, in 2019, the FDA approved a drug called Spravato. It's a nasal spray that contains a version of ketamine, and it's specifically for patients with major depression who haven't been helped by other drugs.

KWONG: OK. So a lot has changed in the world of ketamine, and this sounds like possibly lifesaving treatment. And that must mean researchers are hopeful about what other psychedelic drugs could do. So what else are researchers looking at?

HAMILTON: Well, one thing they're looking at is psilocybin. It's the substance that makes, you know, some mushrooms magic or, if you want to sound like a scientist, psychoactive.

KWONG: Right. And with a psilocybin trip, there's a sense of, like, peacefulness and happiness and of being somehow disengaged from your surroundings.

HAMILTON: Yeah. It can also, though, sometimes cause nausea and really frightening hallucinations. Anyway, researchers did a lot of experiments with psilocybin back in the '60s. That was when a pharmaceutical company, Sandoz, was making a synthetic version of the drug for research purposes. So scientists could get these little pink pills to give to people in their studies. That pretty much ended in the U.S. when the Controlled Substances Act was passed in 1970. At that point, psilocybin became what's known as a Schedule 1 drug - so in the same legal category as heroin. But now there's a lot of interest in treating anxiety, depression and addiction with something called psilocybin-assisted therapy.

KWONG: Yeah. How does that therapy work?

HAMILTON: I will let Alan Davis explain it. He's on the faculty of the Ohio State University and also works at Johns Hopkins University. Here's how he described a therapy session using psilocybin.

ALAN DAVIS: They have a blindfold on. They have headphones on, listening to music. And we really encourage them to go inward and to experience whatever is going to come up with the psilocybin. And then at the end of the day, we have time for reflection and to talk about what their experiences were before sending them home with a support person.

KWONG: Wow. Yeah. Psilocybin-assisted therapy just sounds extremely different from the usual talk therapy.

HAMILTON: Oh, yeah. Yeah. And at least two scientific studies have found that it actually works. What Alan Davis was describing there was part of a randomized clinical trial of 24 people with major depressive disorder, and he told me the results with psilocybin were a lot like the early results with ketamine. So I should add that drug companies in both the U.S. and Europe are now doing larger studies of psilocybin with the goal of eventually bringing a prescription version to market.

KWONG: OK. So, Jon, we've talked about the promise of these drugs, of ketamine and psilocybin specifically. But I'm curious how exactly they work on a neurochemical level because they sound just very different from drugs like Prozac or Zoloft that we're so familiar with for treating depression.

HAMILTON: Yeah, they're definitely different. They target different systems in the brain. And scientists say they seem to help rewire our brain circuits. So, for example, there's evidence that all of these drugs cause the brain to somehow make lots of new connections between brain cells. The drugs also seem to cause some existing connections to weaken or fade away. And there may be something else going on, something that's related to this out-of-body experience these drugs can produce. It's called dissociation - right? - a state where you no longer feel connected to your own body or even your own thoughts and feelings. And that state may actually make it easier for people to evaluate what's going on in their own head.

KWONG: Yeah. I just find that really incredible. So clearly, these drugs work in a very different way. And I'm wondering, which is more therapeutic in the long run - the brain rewiring part or the dissociation part? Do we even know?

HAMILTON: No. And there's a lot of debate about whether dissociation is necessary if you want to use psychedelic drugs to treat psychiatric disorders. I talked to Dr. Ken Solt. He's an anesthesiologist at Harvard Medical School, and he thinks that dissociation is important, at least with ketamine.

KEN SOLT: There seems to be this link between dissociation and the anti-depressive effect of ketamine because if you don't give enough to at least induce dissociation, it seems like you won't get this anti-depressive effect.

HAMILTON: But that may not be true with other psychedelic drugs. So late last year, scientists published a paper about this tweaked version of the drug ibogaine. The version you get from plants will cause hallucinations and dissociation. But this synthetic version, called TBG, has been altered to eliminate those effects. Even so, when scientists gave TBG to mice who'd been bingeing on alcohol, the mice cut way back. And when they gave it to mice with behaviors associated with depression, the mice got better.

I talked about the ibogaine study with Gabriela Manzano. She's a post-doctoral researcher at Weill Cornell Medicine in New York. Manzano told me that if scientists could make safer versions of other psychedelic drugs, it might allow doctors to prescribe these drugs to lots of people instead of just those with no other options.

GABRIELA MANZANO: Ketamine, for example, has huge effects on depression. But it has some really - some side effects that we would like to get rid of. So this provides a roadmap on how we could start tweaking these chemical compounds to make them very useful in the clinic - keep the good parts, get rid of the bad parts.

KWONG: Got you. All right. Well, Jon, you have been reporting on brain science and depression for a long time. What is your take on these drugs?

HAMILTON: I think they are a sign that we're probably at the beginning of a new era in drug treatment for depression and anxiety and maybe for addiction and PTSD as well. I mean, the FDA approved Prozac for depression way back in 1987. And for, like, the next 30 years, there was really nothing new. You had drugs like Paxil and Zoloft come along, but they worked pretty much the same way as Prozac. But when ketamine got approved in 2019, suddenly there was a depression drug on the market that did something totally different in the brain. And now it looks like there will be other drugs based on psychedelics that will be able to help a lot of people who haven't really been helped by anything else before.

KWONG: Well, Jon, thank you for bringing this reporting on a kind of watershed moment for psychedelic drugs. And we look forward to having you on the show to talk more about them.

HAMILTON: Always a pleasure, Emily.

 
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Can AI, or digital tools generally, help us gather more precise data so that we can be more effective clinicians?’

The computer will see you now: Is your therapy session about to be automated?

Experts say AI is set to grow rapidly in psychiatry and therapy, allowing doctors to spot mental illness earlier and improve care. But are the technologies effective – and ethical?

by Ramin Skibba The Guardian | 4 Jun 2021

In just a few years, your visit to the psychiatrist’s office could look very different – at least according to Daniel Barron. Your doctor could benefit by having computers analyze recorded interactions with you, including subtle changes in your behavior and in the way you talk.

“I think, without question, having access to quantitative data about our conversations, about facial expressions and intonations, would provide another dimension to the clinical interaction that’s not detected right now,” said Barron, a psychiatrist based in Seattle and author of the new book Reading Our Minds: The Rise of Big Data Psychiatry.

Barron and other doctors believe that the use of artificial intelligence (AI) will grow rapidly in psychiatry and therapy, including facial recognition and text analysis software, which will supplement clinicians’ efforts to spot mental illnesses earlier and improve treatments for patients. But the technologies first need to be shown to be effective, and some experts are wary of bias and other ethical issues as well.

While telemedicine and digital tools have become increasingly common over the past few years, “I think Covid has certainly super-charged and accelerated interest in it,” said John Torous, director of the digital psychiatry division at Beth Israel Deaconess medical center in Boston.

Technology currently in development can already prove useful, Barron argues. For example, computer programs known as algorithms could notice whether a person’s facial expressions subtly change over time or whether they’re speaking much faster or slower than average, which might be an indication of them being manic or depressed. He believes these technologies could help doctors identify these signs earlier than they otherwise would have.

Software would gather these data and organize them. Between exams, a doctor could then sift through the data, focusing on a clip of a recording flagged by an algorithm. And other information from beyond the doctor’s office could be brought in, too.

“There’s a lot of data we could get from audio, wearables and other things that trace who we are and what we’re doing that could be used to inform treatments and find out how well treatments are working,” said Colin Depp, a psychiatrist at University of California, San Diego.

If apps or devices show that a person is sleeping poorly or less, or they’re gaining weight, or their social media posts reveal depression-like comments or a different personal pronoun, these could inform a psychiatrist’s diagnosis.

As an example of the potential of AI programs, Depp points to a Veterans Affairs project that looks at clinical records of people who ultimately took their own lives. The computer programs scanned their medical record data and identified common factors that might involve a person’s employment and marital status, chronic health conditions, or opioid prescriptions. Researchers believe that their algorithm has already recognized other people who are at risk and disengaged from care – before they become suicidal and before they’d be picked up through traditional channels.

In recent years researchers have also suggested that depression and other mental illnesses can be predicted from the text of people’s Facebook and Twitter posts by spotting words often associated with typical depressive symptoms like sadness, loneliness, hostility and rumination. Changes in a person’s posting patterns could alert a clinician that something’s wrong.

Indeed, in 2017, Facebook developed an algorithm that scanned English-language posts for text that included suicidal thoughts. If such language was identified, the police would be alerted about the post’s author. (The move attracted criticism, not least because the company had, in effect, engaged in the business of mental health interventions without any oversight.)

“Mental illness is under-diagnosed by at least 50%, and AI can serve as a screening and early warning system,” said Johannes Eichstaedt, a psychologist at Stanford University. But current detection screening systems haven’t been proven to be effective yet, he said. “They have mediocre accuracy by clinical standards – and I include my own work here.”

So far, he gives current AI programs a C grade for accuracy, and they can’t yet beat old-fashioned pen-and-paper surveys, he argues.

One of the problems with the algorithms that Eichstaedt and others are developing, he notes, is that they track a sequence of facial expressions or words, but these are only hazy clues to someone’s inner state. It’s like a doctor recognizing apparent symptoms but not being sure what illness is causing them.

Some advocates may be overconfident about the potential of AI to interpret human behavior, cautions Kate Crawford, a researcher at New York University and author of the new book, Atlas of AI. She noted the recent scandal over Lemonade, an insurance company that claimed to use AI to analyze video recordings that its customers submitted when making claims – and which Lemonade said could detect if the customer was being untruthful or fraudulent.

They have mediocre accuracy by clinical standards – and I include my own work here. -Johannes Eichstaedt

This “demonstrates that companies are willing to use AI in ways that are scientifically unproven, and potentially harmful, such as trying to use ‘nonverbal cues’ in videos”, Crawford says in an email. (In a statement to Recode, Lemonade later said "its users aren’t treated differently based on their appearance, disability, or any other personal characteristic, and AI has not been and will not be used to auto-reject claims.”)

Crawford points to a systematic review of the science in 2019, led by psychologist and neuroscientist Lisa Feldman Barrett, which showed that while under the best recording circumstances, AI can detect expressions like scowls, smiles and frowns, algorithms cannot reliably infer someone’s underlying emotional state from them. For example, people scowl in anger only 30% of the time, Barrett says, and they might otherwise scowl for other reasons having nothing to do with anger, such as when they’re concentrating or confused, or they hear a bad joke, or they have gas.

AI research has not improved significantly since that review, she argues. “Based on the available evidence, I’m not optimistic.” Yet she added that a personalized approach could work better. Rather than assuming a bedrock of emotional states that are universally recognizable, algorithms could be trained on a single person over many sessions, including their facial expressions, their voice and physiological measures like their heart rate, while accounting for the context of those data. "Then you’d have better chances of developing reliable AI for that person," Barrett says.

If such AI systems eventually can be made more effective, ethical issues still have to be addressed. In a newly published paper, Torous, Depp and others argue that, while AI has the potential to help identify mental problems more objectively, and it could even empower patients in their own treatment, first it must address issues like bias.

During the training of some AI programs, when they are fed huge databases of personal information so they can learn to discern patterns in them, white people, men, higher-income people, or younger people are often overrepresented. As a result they might misinterpret unique facial features or a rare dialect.

A recent study focused on the kinds of text-based algorithms for mental health used by Facebook and others found that they “demonstrated significant biases with respect to religion, race, gender, nationality, sexuality and age.” The researchers recommend involving clinicians with more similar demographics to patients, and having those doing the labeling and interpreting trained on their own biases.

Privacy concerns loom as well. Some might balk at having their social media activity analyzed, even if their posts are public. And depending on how data from a recorded therapy session are stored, they could be vulnerable to hacking and ransomware.

No doubt there will be some who are skeptical of the entire endeavor of having artificial intelligence play a larger role in mental health decisions. Psychiatry is part science and part intuition, Depp said. AI won’t replace psychiatrists, but it could supplement their work, he proposes.

“The alliance between the provider and the person getting the service is critically important, and it’s one of the biggest predictors of positive outcomes. We definitely do not want to lose that, and in some ways, the technologies could help support it.”

Considering advances in technology, the issue is no longer merely academic.

“The question is, can AI, or digital tools generally, help us gather more precise data so that we can be more effective clinicians?” Barron asks. “That’s a testable question.”

 
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Are psychedelics the future of psychotherapy?
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Psychologist Alex Belser says psychedelic medicine could herald a mental health renaissance. He’s on the forefront of a boom in research and experimental treatments.

by Timothy Meinch | Discover Magazine | 10 Jun 2021

A lot has changed since the 1990s. That’s when Alex Belser, then an undergrad at Georgetown University, first found a book about LSD psychotherapy.

Back then, hardly anyone was talking positively about psychedelics. The U.S. had recently passed a string of strict anti-drug and crime bills, extending the war on drugs that President Richard Nixon started in 1971. By the late 1990s, medical and industry investment in the field was virtually nonexistent.

Two decades — and several degrees — later, Belser has read far more about psychedelics in medicine. He’s also published his own peer-reviewed papers, guided dozens of patients safely through medically sanctioned trips and advised corporations that are suddenly pouring millions of dollars into the promise of psychedelic-assisted therapy. A recent market report from Financial News Media projected the industry in North America will exceed $6.8 billion by 2027.

The business surge in psychedelics has followed a tidal shift in academic research. Since 2006, researchers at Johns Hopkins University alone have published more than 60 peer-reviewed papers on psychoactive compounds found in magic mushrooms and other plants. In late 2019, the university opened the first-of-its-kind Center for Psychedelic and Consciousness Research. Around the same time, the U.S. Food and Drug Administration (FDA) granted “breakthrough therapy” classification to psilocybin, the so-called “magic” compound found in psychedelic mushrooms. That FDA status helps fast-track the approval of promising pharmaceuticals in trial phases. And Oregon made history in November when the state voted to legalize psilocybin for medical use.

Belser, who holds a doctorate in psychology, has made many contributions to this potential medical renaissance. He’s the founding president of Nautilus Sanctuary, a nonprofit dedicated to psychedelic assisted psychotherapy. He also currently works as chief clinical officer at Cybin Inc., a biotech company focused on psychedelic therapeutics, like using a sci-fi looking helmet that shows real-time blood flow, oxygen levels and other brain activity during a psychedelic experience.

He recently met with Discover over video chat to explain the current state of magic mushrooms, psilocybin and hallucinogenic medicine — and the unlikely academic path that brought him here.

Q: We’re talking about medicine. But terms like psychedelics and magic mushrooms can still sound provocative, or edgy and mystical. Is that language misleading?

A: It’s so hard to know what word to use. This is one of our favorite debates: What do we call these medicines? Psychedelic means “mind-manifesting.” They’re not properly hallucinogens. The medical literature uses that term, but that term doesn’t really help describe them. Other people have used terms like entheogen, which is “manifesting the spirit within,” because people do have very powerful spiritual experiences under these medicines. Some people prefer the term plant medicines.

Q: How do you assess and interpret a spiritual experience, both medically and scientifically?

A: My research has been focused on interviewing people in-depth, asking “What is it that happens for you when you use these medicines?” We also do pre- and post-measures. And we use something called the Mystical Experience Questionnaire and the Hood Mysticism Scale that have been used in scores of trials.

But we consistently find that when people have a spiritual or mystical experience with psychedelic medicine, that predicts whether or not they get better in terms of the symptoms they are having for depression, anxiety or something else. This is incredible because it suggests that it’s not just a biomechanical medicine. It’s not just happening in the physiological level. It suggests that people are also having something really important happening in their mind, in their memory and their identity or their history. It’s their relationship to being alive, in the human body and the world. That helps them get better, and that’s independently predicting their treatment outcome.

Q: Interesting. That sounds a bit more like religion, or an existential belief system, than medicine.

A: This is a different model than the traditional “take a pill a day and call me later” approach. It really requires a lot from the person who’s taking the medicine to navigate internally what comes up for them. And it also requires a lot from the people they work with, the clinicians.

When people say, “I felt a profound experience of unity, and an interconnectedness with all things,” it’s not the same as a blood draw or getting a level on your blood pressure. It’s not a metric like that, but it is a way for people to tell you what they’re experiencing and to get at what’s happening internally. If we only paid attention to what we could obviously measure, we would lose everything that happens internally for people in their own minds and their own inner experience, which is the vast majority of what people experience in their lives. This is especially true when you’re dealing with things like depression and addiction and end-of-life distress.

Q: What other symptoms or conditions does this type of treatment work well for?

A: For many psychedelic medicines, they are medicine in search of a condition. So, with psilocybin, it’s potentially effective for a variety of things, including anxiety, major depressive disorder, treatment-resistant depression, obsessive compulsive disorder, smoking cessation, alcohol-use disorder, even potentially other areas like anorexia and eating disorders. I believe that the future of psychiatry will find psychedelic medicine at its heart. That’s because our old drug classes may not have worked well to begin with and are sort of petering out.

Q: How do you describe the shift in this field over the past decade or so?

A: There’s just been an explosion of research in psychedelics. It used to be that when a new study would come out, we would parcel it out word-for-word, paragraph-by-paragraph, because there was so little research coming out. It was a trickle. Now it’s become a torrent of clinical research studies being initiated and papers being published, demonstrating very promising results for a variety of psychedelic medicines for any number of psychiatric conditions. It’s incredible.

There’s also been this massive interest from the public — from Michael Pollan’s book, How to Change Your Mind, to any number of media outlets that have covered these stories in different ways. It’s because when you talk with patients and when you talk to people doing this work, you realize that the experiences can be beautiful and powerful. The effects for people can be really not only intense, but healing, and in ways that don’t work the same way as our conventional medicines work.

Q: And Oregon legalized psilocybin in the November 2020 election. In application, what does that mean immediately and in the near future?

A: They have created a two-year development period. It’s not like the legislation passed, and then, overnight, psychedelic-assisted psychotherapy is legal. The measure is specifically about psilocybin, the active compound in magic mushrooms. These are mushrooms that grow on the six inhabited continents of the world and have been used by human civilizations and peoples in documented anthropological literature for a long time. We expect this is going to be a rulemaking period, and then, psilocybin-assisted psychotherapy treatment for certain conditions will be legal to do by licensed clinicians in the state of Oregon only. And that sort of work may serve as a model for how other states or municipalities could potentially pursue this sort of clinical track. The Oregon approach is like a state-by-state legalization pathway. But psilocybin is still an illegal drug to use from a federal-statutes perspective.

Q: It sounds like the same path we’ve seen with legalizing cannabis in states around the country. Are there a lot of parallels to marijuana?

A: Well, I think it’s an experiment in federalism. In 1970, Richard Nixon signed the Controlled Substances Act into law, and it’s been an exemplar law, not just for the U.S., but for countries around the world. But, when states like Oregon can change their state laws regarding how we can return to these medicines, it opens up a new field. And these medicines do show medical and psychiatric benefit for people, and the evidence suggests they are not addictive or dependence-causing.

But there’s an important distinction from cannabis: Cannabis is sold, even if it’s prescribed, as a product without supervision or without working with a facilitator. Psychedelic medicines are a very different class because nobody is seriously proposing that people should just be prescribed psilocybin for at-home use as we do with cannabis —at least not at significant doses. This is really a combination treatment. It would be a medicine that would be prescribed by a person who has specific training in doing psychedelic-assisted medical intervention work.

Q: That’s where practitioners like you come in — in your case, with 20 years of experience. But how did you get here, given the lack of activity in the field when you were in college?

A: I was a kid, an undergrad at Georgetown in the ’90s, and I read a book called LSD Psychotherapy: The Healing Potential of Psychedelic Medicine by psychiatrist Stanislav Grof. I just was so fascinated by these medicines and I flew to my first psychedelic conference and met all of the psychedelic leaders in the field at the time. The research movement [that gained momentum in the 1960s] had largely stalled out, but the traditions were alive and a lot of people knew that these could be promising medicines. I wasn’t even pursuing psychology at that time. I was doing prison-reform work, working in jails and prisons in D.C., Maryland, Virginia, and then I moved to the United Kingdom for a master’s in criminology.

I tacked from there to working with LGBTQ+ people. My dissertation in psychology was on how to prevent suicide among lesbian, gay and bisexual teenagers. Because in that group, a lot of people feel like they want to end their lives in part because of the shame and stigma that they’ve received. We started a psychedelic research group at NYU in 2006, when I was just a graduate student. I got to help run a number of studies at NYU. I did my clinical research fellowship at Yale. And there I worked on a number of psilocybin studies. I’ve also worked on MDMA therapy studies for people with severe PTSD, including a vet from Afghanistan who had been pinned down in multiple firefights.

Q: That seems like an atypical path, especially for someone now working in pharmaceuticals. How does that foundation inform your work today?

A: I think it’s important to have a social justice framework when working in medicine, broadly and specifically in psychedelic medicine. There’s no way to do this work without attending to our participation in structures that might oppress people and our ability to make changes so that we can treat each other with compassion, dignity and deep respect. Our practice of medicine should mirror and amplify that for the betterment of all people.

Q: You mentioned earlier that psychedelic treatment isn’t really a pill-a-day model. Can you elaborate on that and how it fits into the current system of modern medicine?

A: I think that these are medicines for the whole person, and I think it’s important that we understand them as such. It’s not going to work to try to fit psychedelic medicine and practice into old models. We have to think differently about how we work with these medicines. When I say the whole person, I really do mean not just the body, but the mind and the person’s experience of their spirit and how they make meaning of their lives.

There is a long lineage of psychedelic plants and medicines being used by people across the planet. Western medicine kind of fell asleep on it for the last 100 years. And not all of those practices are still alive, and maybe not all of them will be helpful for us today. But the psychiatric possibility of this sort of medicine is really a different way of asking, “What could healing be?” I think that psychedelic medicine and the research suggests we should think very deeply about how we practice medicine.

*From the article here :
 
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Could the embrace of psychedelics lead to a mental health revolution?

by Maya Singer | Vogue | 12 Feb 2021

AT SEVEN O’ CLOCK on a recent evening, I dim the bedroom lights, call out a reminder to my boyfriend to rouse me in an hour with a gentle tap, and close the door. “Have a great trip,” I hear him say from the living room as the two ketamine tablets I’ve pressed into the pockets of my cheeks dissolve, leaving a bitter residue. Minutes later, I’m flying over water that reflects a sourceless golden light. Am I the light? The thought triggers a sensation of being stretched like taffy in all directions. It’s not my body being stretched—I don’t have a body anymore—but the immaterial me moving in tune with the ambient music in my headphones. I stretch and spread until at last I’ve dissolved—pixelated—at which point a small voice in my head calls out, “Do you really think this will help you quit smoking?”

The last time I was on ketamine, I was hooked up to an IV following surgery. This time, the drug—in general medical use as an anesthetic since 1970—arrived on my doorstep courtesy of Mindbloom, a new telemedicine company specializing in ketamine-based psychedelic therapy. This was no shady dark-web deal: Prescribed by a psychiatric nurse practitioner following an extensive intake evaluation, and compounded by a licensed pharmacy, the ketamine came bundled with an eye mask, a hardbound journal, and a blood-pressure cuff that I was instructed to use before and after dosing, to test my vitals. The tablets themselves were housed in a mirrored pouchette with the tagline ACHIEVE YOUR BREAKTHROUGH spelled out in sleek, sans serif font. I was tempted to post a shot to Instagram, but I had a Zoom call with my psychedelic-integration coach in half an hour, and I wanted to meditate first.

Welcome to the brave new world of psychedelic wellness. After decades underground, psychedelics such as ketamine, LSD, psilocybin, and MDMA are getting a fresh look from the medical establishment, thanks to myriad studies suggesting silver bullet–like efficacy in the treatment of anxiety, depression, and addiction, among other ailments. MDMA, renowned for its bliss-inducing effect—hence the street name “ecstasy”—is on course to be approved for the treatment of post-traumatic stress disorder (PTSD) within the next year or two. Synthetic forms of psilocybin, the active compound in magic mushrooms, were given “breakthrough” designation by the FDA in 2018, allowing for fast-tracking of drug trials. Meanwhile, this past November, Oregon became the first state in the nation to legalize psilocybin for medical use, an advance not lost on the investors flocking to start-ups like MindMed and Compass Pathways, both of which are developing psilocybin treatments in anticipation of a cannabis-style psychedelics boom. A mental-health revolution is at hand—and it’s long overdue, according to experts such as Frederick Streeter Barrett, Ph.D., assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine and a faculty member at the university’s recently opened Center for Psychedelic & Consciousness Research.

“The current model for treating problems like anxiety and depression just isn’t very good,” Barrett says. “Patients take pills every day, for years, and these medications not only have nasty side effects, they often don’t even work. But with psychedelics-assisted therapy, there’s the potential to truly alter someone’s life with just one or two sessions, because you’re getting at suffering at the source.”

I’m not suffering, exactly, but for lack of more technical language, I’ve kind of been freaking out. Straining to maintain a productive work schedule under lockdown, I fell back into the habit of smoking as I write—and soon thereafter, the habit of trying to quit. The addiction struck me as fundamentally psychological: If I was so hooked on nicotine, why did I reach for my American Spirits only when I was stuck at my desk, staring down a deadline? But reach for them I did, and the harder I worked not to—with the aid of gum, apps, hypnosis, you-name-it—the more fixated I became on the fear that I simply could not write without cigarettes. I was starting to feel truly hopeless when I stumbled across a news item about studies showing that with the aid of psilocybin, longtime smokers were quitting cold turkey and sticking with it at rates that put all other remedies to shame; two-thirds of participants in one recent study were confirmed cigarette-free after one year!

Intrigued, I did a little more digging and discovered that ketamine—a dissociative hallucinogen that is already legal for supervised medical use, including in the treatment of depression—seemed to draw out the mind in a way similar to psilocybin by putting the brain in a “neuroplastic” state, explains Julie Holland, M.D., a New York–based psychiatrist and the author of the 2020 book Good Chemistry. “They have different chemical properties, but both ketamine and psilocybin have an ego-dissolving effect, where you’re breaking the mental loop that’s symptomatic of conditions like depression and anxiety and addiction, and allowing the brain to form new connections.”

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Maybe a little ego-dissolution was the answer, I mused as I stamped out another butt in the ashtray next to my laptop and googled “ketamine therapy—New York.”

“THE TRUTH IS, WE DON'T REALLY know how this stuff works,” Michael Pollan, author of the best-selling psychedelics primer How to Change Your Mind, tells me. “A leading theory is that psychedelics quiet the brain’s ‘default-mode network,’ and that opens up new pathways for thought.” As Pollan goes on to explain, the default-mode network is where “the ego has its address”—it’s the part of our brains where we construct the narrative of who we are and, thus, the place we get stuck in destructive thought patterns about ourselves. “That could be ‘I’m a worthless person who doesn’t deserve love,’ or it could mean telling yourself that you can’t get through the day without smoking,” Pollan continues. “Either way, the idea is that, by muffling those thoughts, psychedelics help you out of the rut.”

Pollan’s précis on the science of psychedelics is reassuringly down-to-earth. For years, I’d been put off by the drugs’ woo-woo connotations, and to judge by the refined, minimalist aesthetics of new ketamine-therapy chains such as Field Trip Health, which has serene locations in New York City, Toronto, Atlanta, Chicago, and Los Angeles, I’m not the only person with zero interest in a tie-dye mental makeover. It’s all a far cry from Timothy Leary and The Electric Kool-Aid Acid Test. But Leary—who famously conducted psychedelics experiments at Harvard in the early 1960s, before he ran afoul of the law and, in turn, helped prompt the criminalization of psilocybin and LSD—does continue to exert an influence: His “set and setting” theory is a cornerstone of all contemporary psychedelics-aided therapy. “Set basically refers to mindset, going into your journey, and setting is your environment,” explains Ronan Levy, who cofounded Field Trip in 2019 after establishing—then selling—Canada’s largest network of cannabis clinics. “They matter as much as the drug you’re taking,” he continues. “You need to be in a place—mentally and physically—where you feel inspired and at ease.”

Because I’d chosen to work with Mindbloom, thanks to their COVID-friendly process, the setting for my four, hour-long treatments, was my bedroom. To be perfectly clear, I wasn’t microdosing. Nor was I popping a pill just to see what colors spilled out of my head. Prior to receiving my Mindbloom package, I spent over an hour on Zoom with a board-certified psychiatric nurse practitioner who quizzed me on everything from my family medical history to my typical responses to stress. (According to Mindbloom founder and CEO, Dylan Beynon, about 35 percent of potential patients are screened out at this point, for reasons such as past experience of psychosis or, at the other end of the spectrum, not meeting the threshold for a diagnosis of anxiety and/or depression.) “Set” was established in conversation with Laura Teodori, my psychedelic-integration-support coach, who—after obtaining confirmation from my boyfriend that he’d check on me every 20 minutes—helped me formulate an “intention” for the trip immediately after our call. My goal, we ascertained, was to recall moments in my life when I could create without smoking. With that in mind, I tucked the tablets inside my mouth, pressed play on the Mindbloom-curated soundtrack that would be piping through my headphones, lowered my eye mask, and waited for my default-mode network to go off-line.

PSYCHEDELICS COME IN MANY FORMS, from the low-dose ketamine I was taking to wallop-packing plant medicines, like ayahuasca and ibogaine and peyote, that have been used in sacred rituals for hundreds, perhaps thousands of years (and that are illegal in the United States). But a feature common to all is the sense of coming into contact with the cosmic. “It’s like there’s no boundary between you and others, or you and the universe,” notes Johns Hopkins’ Barrett, saying that virtually all subjects in psilocybin studies have reported such a feeling of oneness. “Some people call this an experience of God, or nirvana.” I went into my first ketamine journey matter-of-factly, with a problem to solve, and even so, that first trip commenced with a vision of the world rewinding, a kind of reverse big bang that exposed the heretofore invisible filaments connecting everyone and everything. The vision moved me—tears puddled behind my eye mask—and then it yielded to more personal impressions, such as a recurring image of myself, age six or seven, playing with my dollhouse.

“What do you think was important about the dollhouse?” Teodori asked me in our post-trip call. I was still pretty woozy as we Zoomed—the effect wore off by the next day—but suddenly, it was like a light bulb went on in my head. “I think…I think I was remembering what it felt like to create without smoking,” I told her. “When there wasn’t any pressure, and I could just play.”

This download is part of integration, another cornerstone of modern psychedelic medicine. “The goal is to take advantage of the neuroplastic state, which lasts for about a week after dosing,” explains Beynon. “You want the changes in your brain to stick, so the question becomes, How do you turn these new thoughts into new behaviors?” For me, this entailed finding ways to get back in touch with that dollhouse sense of play.

Easier said than done. My ketamine experiences were clarifying and often even profound, but they didn’t change certain nerve-racking facts of life, such as that I write for a living and thus have deadlines to meet if I wish to pay my bills. Or that it’s hard—like, really hard—to stay motivated in the midst of a global pandemic, when each day brings fresh spurs to panic and depression. “There’s a huge mental-health crisis happening parallel to, and in response to, this pandemic,” notes Benjamin Brody, M.D., assistant professor of clinical psychiatry at Weill Cornell Medicine in New York, and chief of the Division of Inpatient Psychiatry at the university hospital, where ketamine infusions are typically administered. “People who are grieving, people who have lost jobs, people who are feeling disconnected, whose lives have been upended .…” With demand for care rising “across the board,” as Brody notes, it’s no surprise that psychiatrists such as Amanda Itzkoff, M.D., are seeing a huge uptick in inquiries about ketamine therapy. But it may or may not be the right tool for every job, Itzkoff points out.

“The thing is, if you got laid off and you don’t know how you’re going to pay rent, ketamine won’t change that,” says Itzkoff, an early adopter who has been providing ketamine infusions at her Manhattan practice since 2014. “It doesn’t remove the external pressures. But when you’ve got someone with severe depression, who has kind of given up, then there’s real promise in this treatment.” Itzkoff cites the example of a former patient, a high-powered attorney and mother of two, who was on disability and “almost catatonic” when they began working together. “She had to be retrieved from this state,” recalls Itzkoff. “By breaking the negative thought loop—even temporarily—you show someone it’s possible to feel another way. And that,” she adds, “can be channeled toward getting people back on their feet.”

Chad Kuske didn’t just get back on his feet following his first psilocybin treatment a year and a half ago; he experienced what he calls an immediate and profound “sense of meaning and a desire to live.” A former Navy SEAL, Kuske, 40, had tried psychoanalysis and various pharmaceuticals before being medically retired from the service in 2017. Reentering civilian life, he found himself using drugs and alcohol as a way of coping with the anxiety, depression, and alienation that he now comprehends as the symptoms of PTSD. “Nothing else had worked. And I knew that sooner or later, if I kept doing things the same way, my life would be over—either literally or metaphorically, like I’d wind up in jail,” Kuske explains. “The mushrooms helped me see my situation clearly: I was in hell, but it was a hell of my own creation, and I could make the choice whether to stay there and suffer or leave and start the work of changing.”

One of the key insights Kuske has taken away from his trips—and from his integration process, which is ongoing—is that he’s not alone in struggling to meet the challenges of daily life. Likewise, Itzkoff suggests that the feeling of interconnectedness induced by psychedelic therapy—and near-psychedelics, such as ketamine and MDMA—may help alleviate the isolation brought on by COVID. It may also play a role in helping the people hardest hit by the pandemic recuperate: Nautilus Sanctuary, a nonprofit psychedelics-research and training center in New York, is already planning a study exploring the use of MDMA to treat frontline workers with severe PTSD—one of the many inquiries to expand on the drug’s groundbreaking FDA trials sponsored by MAPS, which entered phase three in 2017. Other studies sponsored by the organization have focused on veterans in Israel and the United States, and the Department of Veterans Affairs has exhibited a willingness to approve such studies, so long as they are safe, beneficial, and scientifically sound.

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This kind of conservative approach is merited, notes Weill Cornell’s Brody. “I’m very concerned about this atmosphere, that the floodgates are opening. I work with ketamine, a drug that’s been in use for decades, and even there, we don’t know all that much about its long-term effects,” says Brody, who provides ketamine-infusion therapy only to patients in whom he’s observed severe, treatment-resistant depression—and who was positively aghast when I relayed rumors that self-dosing with inhalers of esketamine, a synthetic form of the drug given FDA approval for supervised use in 2019, was all the rage in L.A. “Ketamine is a serious drug!” he reiterates. “This isn’t a spa service. It’s not like getting Botox. And what worries me about all these clinics popping up is that people are going to start thinking about it that way.”

Brody is hardly alone in fearing the commercialization of psychedelics—a trend that, if canny investors like Peter Thiel, a backer of Compass Pathways, are correct, is on pace to increase rapidly. “It’s a unique space because so much of the technology has been developed by Indigenous healers,” notes Pip Deely, co-founder of the venture-capital firm Delphi, which is eyeing investments in psychedelics start-ups and supporting a new psilocybin-legalization campaign in Hawaii. “We see a lot of dread that if this all goes the way of cannabis, the people who have been doing this work the longest will be cut out of the conversation, and those Indigenous roots will be erased.” Unprompted, I hear a version of this concern from one Berkshires-area healer who, for legal reasons, prefers to remain unnamed; she tells me that, although she supports expanding access to psychedelics, she worries about the experience becoming pro forma and “clinical.”

Though they come at their misgivings from opposite angles, both traditional healers and Brody are wary of psychedelics’ getting marketed as a quick fix—and in all honesty, I’m the target demographic for that pitch. When I sat down at my computer to fill out Mindbloom’s candidate questionnaire, what I wanted was to detangle a few mental wires. By the time I’d completed my final ketamine treatment, I’d come to realize that those wires were crossed very deep down: My writing-while-smoking problem was really a problem with the little voice in my head telling me that I’m not good enough, I haven’t achieved enough, I’m falling behind. As I wrote in my integration journal after my second session, “Every little deal is a big deal.” I added a frowny face to underline the point.

I can’t blame Mindbloom for my failure of mindset. All my conversations with Teodori were oriented around getting me to probe the heart of my fears, and she was diligent in supporting me as I attempted to integrate the lessons of my journeys into daily life, checking in with me every few days via text and reminding me that she was always available to talk. Alas, I didn’t take her up on that offer as often as I should have—I had a ton of writing to do!—and in the end, I felt changed but not transformed. Which could be a me thing, or it could be a drug thing. Barrett of Johns Hopkins pointed me to studies from the university’s Center for Psychedelic & Consciousness Research indicating that, where smoking cessation is concerned, the more “mystical” the trip, the more effective the treatment. “There’s a big difference between a low dose of ketamine and taking what we call a ‘breakthrough’ dose of psilocybin,” he notes. “That’s where you’re really going to break down your sense of self.”

Is that what I want? Is that what we all want, in some subconscious way? “There’s a spiritual hunger these medicines satisfy,” Pollan points out, and I can attest that once you’ve visited the astral plane, you want to go back. Most hallucinogens are not physically addictive, but the psychedelic experience is itself addicting. I spoke to numerous people for this story who described their encounters with psychedelics as “life changing” in ways large and small; one woman even credited peyote with restoring movement to her paralyzed arm. But Ann Watson’s account is the most relatable. A former VP and fashion director at Henri Bendel in New York City, and now a cochair of The Vaquera Group, a global marketing firm, Watson, 52, is also a self-described “explorer” who, like me, kept a pretty tight lid on her deepest, darkest feelings—until she began working with psychedelics 12 years ago. “My childhood was chaotic; there was a lot of abandonment, but I didn’t associate with the word trauma, because I thought it was reserved for people who have experienced things like rape or war. But I was seeking something,” explains Watson, who tried a variety of treatments to relieve an “ever-present vibration of anxiety,” including counseling and prescribed antidepressants, before experimenting with a long list of psychedelics. Eventually she arrived at a treatment plan with a doctor in Los Angeles she sees four times a year for guided psilocybin trips; she also microdoses psilocybin on a more regular basis, mixing magic mushrooms with Lion’s Mane. “It’s an ongoing process,” she tells me. “The thing is, once you start looking inward, you realize there’s always more to see.”

Perhaps that is the main takeaway from my own journey: that I’m just at the start of it. I have work to do on myself. But in the meantime, I also have work to do, period—as in, I’m on deadline for this piece. And I regret to inform you that as I write these words, I am indeed smoking.

 
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Is Psychiatry Ready for Medical MDMA?

by Gillinder Bedi | The Conversation | 28 Mar 2018

Within five years, science will likely have answered a controversial question: can methylenedioxymethamphetamine (MDMA) treat psychiatric disorders?

After some studies showing a positive effect, MDMA-assisted psychotherapy is entering final clinical trials as a treatment for post-traumatic stress disorder (PTSD). If these trials show positive results, MDMA will go from an illegal drug to a prescription medicine in the United States by 2021, potentially prompting movement in this space in Australia and Europe.

MDMA would move from the fringes to mainstream psychiatry, becoming recognised as a mainstream treatment option. What remains less clear is how psychiatry will deal with questions arising from this new treatment approach.

MDMA in medicine: a brief history

German pharmaceutical company Merck patented MDMA in 1912. However, it appears not to have been used in humans until later that century.

Better known as a street drug in the rave scene of the 1980s and ’90s, MDMA was used in the 1970s by a small band of US psychiatrists and therapists. This group believed it enhanced the therapeutic bond and improved treatment for ailments ranging from marital distress to, potentially, schizophrenia.

Following rebranding as “ecstasy”, large-scale recreational use of MDMA led to its 1985 listing as an illegal drug in the USA (Australia followed in 1986). The MDMA-therapy community unsuccessfully protested against this designation.

Advocates for MDMA-assisted psychotherapy have been playing the long game ever since, undertaking a painstaking process of research and advocacy, which has culminated in the upcoming trials.

MDMA versus ecstasy

Advocates for MDMA-assisted psychotherapy have been at pains to distinguish the street drug ecstasy from MDMA the medicine. Ecstasy can contain a range of substances as well as varying doses of MDMA.

This is unsurprising given early evidence that high repeated MDMA doses – more relevant for recreational than therapeutic use – damage serotonergic neurons in animals.

Catastrophic predictions of a lost generation of ecstasy users, however, failed to materialise. Indeed, numerous people have received MDMA doses similar to those proposed for therapy in laboratory studies. This shows that MDMA can be safely administered under controlled conditions to well-screened healthy adults.

It remains unknown whether the same is true of groups excluded from most studies. This includes children and older people, and those with psychiatric or physical illnesses. Studies to date do, however, suggest acceptable safety in adults with PTSD.

Pharmacologically enhanced treatment

One aspect of MDMA therapy attracting less attention is that it involves a fundamental shift in psychiatric medication. All currently approved psychiatric medications treat symptoms rather than the disease itself. Relapse is common after stopping treatment.

MDMA-assisted psychotherapy, by comparison, involves limited MDMA doses over two or three sessions of eight to ten hours. The aim is to “fast-track” psychotherapy to produce long-lasting changes.

Possible mechanisms of such an effect are unclear. One suggestion is that the effects of MDMA, such as feelings of empathy, openness and reduced fear, might allow people to reprocess traumatic memories during psychotherapy.

Other medications are also being considered as adjuncts for psychotherapy. These include potent psychoactives like LSD and psilocybin, or drugs thought to enhance psychotherapy via mechanisms other than psychoactive effects.

It is possible, however, that a broader range of pharmaceuticals could be used in this way. Thus, a potential benefit of MDMA’s approval could be to spur further research in this area.

The challenges of regulation

The potential approval of MDMA for prescription gives rise to pressing questions about regulation. For instance, should prescribing be limited to physicians with specific qualifications? What training should be required for those conducting the psychotherapy? How should the drug be handled and stored by pharmacists?

The combination of a drug-affected patient with non-drug-affected therapists could make patients vulnerable during psychotherapy. This suggests a need for stringent training and oversight of MDMA-assisted therapy.

Approval of MDMA will also lead to off-label prescribing, with doctors prescribing the drug for conditions other than PTSD. This could include a range of conditions, such as depression and substance use disorders, and various patient groups.

A particular issue is prescribing to children/adolescents. To date no controlled studies have assessed the safety of MDMA in young people. Planned studies in adolescents with PTSD will thus be important.

Is anything ‘penicillin for the soul’?

The slow progression of MDMA-assisted psychotherapy from the subcultural margins towards approval has been driven by the belief of those advocating for it.

Without this motivated community, MDMA would likely not have been developed as a medication, as it is off patent. The downside of this robust advocacy base is that it can lead to rather extreme claims (e.g. “penicillin for the soul”) and experimenter bias.

In addition to well-designed studies that control for experimenter bias, there is a need for researchers and clinicians outside the MDMA-advocacy community to be involved in the ongoing development of this research direction.

If MDMA is to become a part of mainstream psychiatry’s armamentarium, many questions will need to be answered. The next few years will be critical to see if MDMA joins the ranks of failed psychiatric treatments, or offers new hope to people suffering from PTSD.

https://theconversation.com/is-psychiatry-ready-for-medical-mdma-94105
 
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