Psychedelic drug MDMA faces questions as FDA considers approval for PTSD

Federal health regulators are set to review the first request to approve the mind-altering club drug MDMA as a treatment for PTSD

MATTHEW PERRONE 

AP health writer

May 31, 2024, 

WASHINGTON -- Federal health regulators are questioning the safety and evidence behind the first bid to use MDMA, the mind-altering club drug, as a treatment for PTSD, part of a decadeslong effort by advocates to move psychedelic drugs into the medical mainstream.

The Food and Drug Administration posted its initial review of the drug Friday, ahead of a meeting of outside advisers who could help decide whether MDMA — currently illegal under federal law — becomes the first drug of its kind to win U.S. approval as a medication. The experts will discuss the quality of the evidence and safety concerns Tuesday, including MDMA's potential for abuse, before taking a nonbinding vote on the drug's overall benefits and risks. The FDA will make the final decision, likely in August.

In their assessment, FDA scientists said that patients who received MDMA and talk therapy showed “rapid, clinically meaningful, durable improvements in their PTSD symptoms,." But they also called the research “challenging to interpret,” and questioned how long the benefits might last. They said it’s difficult to know how much of the improvement came from MDMA versus simply undergoing intensive therapy, and also raised several safety concerns, including MDMA's potential to cause heart problems.

Post-traumatic stress disorder is closely linked to depression, anxiety and suicidal thinking and is more prevalent among women and veterans. Currently antidepressants are the only FDA-approved drugs for the condition.

If approved, MDMA would be reclassified as a prescription medicine and made available to specially certified doctors and therapists. Currently the drug is in the same ultra-restrictive category as heroin and other substances the federal government deems prone to abuse and devoid of any medical use.

MDMA, also known as ecstasy or molly, is the first in a series of psychedelics that are expected to be reviewed by the FDA in coming years. It’s part of a resurgence of research into the potential of psychedelics for hard-to-treat conditions like depression, addiction and anxiety. MDMA's main effect is triggering feelings of intimacy, connection and euphoria.

Companies are studying MDMA, psilocybin, LSD and other mind-expanding drugs for numerous mental health problems.

Until recently, psychedelic research was mainly funded by a handful of nonprofit advocacy groups, including Multidisciplinary Association for Psychedelic Studies, or MAPS. The company seeking approval for MDMA, Lykos Therapeutics, is essentially a corporate spinoff of MAPS, which conducted all the studies submitted for FDA review.

In two MAPS studies, patients received MDMA as part of an intensive, four-month course of talk therapy lasting more than a dozen sessions, only three of which involved taking the drug. The drug is thought to help patients come to terms with their trauma and let go of disturbing thoughts and memories.

The group studied its approach in 195 adults with moderate-to-severe PTSD who were randomly assigned to undergo the therapy with MDMA or with a dummy pill. Following treatment, patients who received MDMA had significantly lower PTSD scores and were more likely to be in remission.

But FDA reviewers noted that the vast majority of patients correctly guessed whether they had received MDMA or a dummy pill, making it “nearly impossible” to maintain the so-called “blinded” objectivity considered essential for high-quality drug research. The agency also questioned how long the drug's benefits might last. MAPS tracked some patients for up to two years, but reviewers noted that about a quarter of patients quickly dropped out of the follow-up study, limiting the usefulness of the results.

The most common side effects of MDMA included headache, nausea, muscle tightness and decreased appetite. More serious issues included heart palpitations and elevated blood pressure, which FDA reviewers said had the “potential to trigger” life-threatening heart problems.

They also raised concerns about the potential for patients to abuse MDMA, which functions similarly to amphetamines and other stimulants.

While MDMA would be a first-of-a-kind approval, U.S. doctors and the FDA itself have already laid some of the groundwork for working with drugs that can cause intense, psychological experiences.

Hundreds of clinics across the U.S. already offer ketamine — the powerful anesthetic sometimes used as a party drug — to treat a host of ailments, including depression, anxiety, chronic pain and PTSD. The FDA has only formally approved the drug for use during surgery, but its availability allows doctors to prescribe it “off-label” for various mental and physical ailments.

In 2019, the FDA approved Johnson & Johnson’s proprietary form of the drug, Spravato, a nasal spray that treats severe depression. Similar to ketamine, the drug is offered at doctor’s offices and clinics where patients usually spend several hours reclining in a chair.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

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Weed beats booze as daily marijuana use outpaces drinking in definitive nationwide study of tens of millions of people

BYCARLA K. JOHNSON AND THE ASSOCIATED PRESS
May 22, 2024 

Marijuana is really popular.
JEFF CHIU—AP PHOTO

Millions of people in the U.S. report using marijuana daily or nearly every day, according to an analysis of national survey data, and those people now outnumber those who say they are daily or nearly-daily drinkers of alcohol.

Alcohol is still more widely used, but 2022 was the first time this intensive level of marijuana use overtook daily and near-daily drinking, said the study’s author, Jonathan Caulkins, a cannabis policy researcher at Carnegie Mellon University.

“A good 40% of current cannabis users are using it daily or near daily, a pattern that is more associated with tobacco use than typical alcohol use,” Caulkins said.

The research, based on data from the National Survey on Drug Use and Health, was published Wednesday in the journal Addiction. The survey is a highly regarded source of self-reported estimates of tobacco, alcohol and drug use in the United States.

In 2022, an estimated 17.7 million people reported using marijuana daily or near-daily compared to 14.7 million daily or near-daily drinkers, according to the study.

From 1992 to 2022, the per capita rate of reporting daily or near-daily marijuana use increased 15-fold. Caulkins acknowledged in the study that people may be more willing to report marijuana use as public acceptance grows, which could boost the increase.

Most states now allow medical or recreational marijuana, though it remains illegal at the federal level. In November, Florida voters will decide on a constitutional amendment allowing recreational cannabis, and the federal government is moving to reclassify marijuana as a less dangerous drug.

Research shows that high-frequency users are more likely to become addicted to marijuana, said Dr. David A. Gorelick, a psychiatry professor at the University of Maryland School of Medicine, who was not involved in the study.

The number of daily users suggests that more people are at risk for developing problematic cannabis use or addiction, Gorelick said.

“High frequency use also increases the risk of developing cannabis-associated psychosis,” a severe condition where a person loses touch with reality, he said.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

Study shows dramatic increase in daily cannabis use in the United States

 

May 22 2024Carnegie Mellon University

Many countries around the world are considering revising cannabis policies. A new study by a researcher at Carnegie Mellon University assessed cannabis use in the United States between 1979 and 2022, finding that a growing share of cannabis consumers report daily or near-daily use and that their numbers now exceed those of daily and near-daily alcohol drinkers. The study concludes that long-term trends in cannabis use parallel corresponding changes in policy over the same period. The study appears in Addiction.

"The data come from survey self-reports, but the enormous changes in rates of self-reported cannabis use, particularly of daily or near-daily use, suggest that changes in actual use have been considerable," says Jonathan P. Caulkins, professor of operations research and public policy at Carnegie Mellon's Heinz College, who conducted the study. "It is striking that high-frequency cannabis use is now more commonly reported than is high-frequency drinking."

Although prior research has compared cannabis-related and alcohol-related outcomes before and after state-level policy changes to changes over the same period in states without policy change, this study examined long-term trends for the United States as a whole. Caulkins looked at days of use, not just prevalence, and drew comparisons with alcohol, but did not attempt to identify causal effects.

The study used data from the U.S. National Survey on Drug Use and Health (and its predecessor, the National Household Survey on Drug Abuse), examining more than 1.6 million respondents across 27 surveys from 1979 to 2022. Caulkins contrasted rates of use in four milestone years that reflected significant policy change points: 1979 (when the first data became available and the relatively liberal policies of the 1970s ended), 1992 (the end of 12 years of conservative Reagan-Bush-era policies), 2008 (the year before the U.S. Department of Justice signaled explicit federal non-interference with state-level legalizations), and 2022 (the year for the most recent data available). Among the study's findings:

• Reported cannabis use declined to a low in 1992, with partial increases through 2008 and substantial growth since then, particularly for measures of more intensive use.
• Between 2008 and 2022, the per capita rate of reporting past-year use increased 120%, and days of use reported per capita increased 218% (in absolute terms, the rise was from 2.3 billion to 8.1 billion days per year).
• From 1992 to 2022, the per capita rate of reporting daily or near-daily use rose 15-fold. While the 1992 survey recorded 10 times as many daily or near-daily alcohol users as cannabis users (8.9 million versus 0.9 million), the 2022 survey, for the first time, recorded more daily and near-daily users of cannabis than of alcohol (17.7 million versus 14.7 million).
• While far more people drink than use cannabis, high-frequency drinking is less common. In 2022, the median drinker reported drinking on 4-5 days in the previous month versus using cannabis on 15-16 days in the previous month. In 2022, prior-month cannabis consumers were almost four times as likely to report daily or near-daily use (42% versus 11%) and 7.4 times more likely to report daily use (28% versus 3.8%).

These trends mirror changes in policy, with declines during periods of greater restriction and growth during periods of policy liberalization."

Jonathan P. Caulkins, professor of operations research and public policy at Carnegie Mellon's Heinz College

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He notes that this does not mean that policy drove changes in use; both could have been manifestations of changes in underlying culture and attitudes. "But whichever way causal arrows point, cannabis use now appears to be on a fundamentally different scale than it was before legalization."

Among the study's limitations, Caulkins says that because the study relied on general population surveys, the data are self-reported, lack validation from biological samples, and exclude certain subpopulations that may use at different rates than the rest of the population.

Source:

Carnegie Mellon University

Journal reference:

Caulkins, J. P., (2024) Changes in self-reported cannabis use in the United States from 1979 to 2022. Addiction. doi.org/10.1111/add.16519.

 Psychedelic drug-induced hyperconnectivity in the brain helps clarify altered subjective experiences

A first of its kind imaging study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging provides insights into how the brain works on psychedelic drugs and their potential use to treat psychiatric disorders

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A NEW STUDY FINDS A PATTERN OF PSILOCYBIN-INDUCED DYNAMIC HYPERCONNECTIVITY IN THE BRAIN, WHICH IS LINKED TO OCEANIC BOUNDLESSNESS.

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CREDIT: BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING

Philadelphia, May 23, 2024 – A new study shows that the use of psilocybin, a compound found in the widely known “magic mushrooms,” initiates a pattern of hyperconnectivity in the brain linked to the ego-modifying effects and feelings of oceanic boundlessness. The findings, appearing in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, help explain the so-called mystical experiences people report during the use of psychedelics and are pertinent to the psychotherapeutic applications of psychedelic drugs to treat psychiatric disorders such as depression.

The concept of oceanic boundlessness refers to a sense of unity, blissfulness, insightfulness, and spiritual experience often associated with psychedelic sessions.

In one of the first brain imaging studies in psychedelic research, investigators found a specific association between the experiential, psychedelic state and whole-brain dynamic connectivity changes. While previous research has shown increases in static global brain connectivity under psychedelics, the current study shows that this state of hyperconnectivity is dynamic (changing over time) and its transition rate coincides with the feeling of oceanic boundlessness, a hallmark dimension of the psychedelic state.

Lead investigator Johannes G. Ramaekers, PhD, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, says, "Psilocybin has been one of the most studied psychedelics, possibly due to its potential contribution in treating different disorders, such as obsessive-compulsive disorder, death-related anxiety, depression, treatment-resistant depression, major depressive disorder, terminal cancer-associated anxiety, demoralization, smoking, and alcohol and tobacco addiction. What was not fully understood is what brain activity is associated with these profound experiences."

Psilocybin generates profound alterations both at the brain and the experiential level. The brain's tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental perspectives. The findings of the new study illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, providing insights into the neurophysiology and neuro-experiential qualities of the psychedelic state.

Dr. Ramaekers adds, "Taken together, averaged and dynamic connectivity analyses suggest that psilocybin alters brain function such that the overall neurobiological pattern becomes functionally more connected, more fluid, and less modular."

Previously acquired functional magnetic resonance imaging (fMRI) data were analyzed for two groups of people; one group of 22 individuals received a single dose of psilocybin, the other 27 participants received a placebo. During the drug's peak effects, participants who received psilocybin reported substantial phenomenological changes compared to placebo. Also, brain connectivity analysis showed that a pattern characterized by global region-to-region connectivity was re-appearing across the acquisition time in the psilocybin group, potentially accounting for the variant mental associations that participants experience.

Moreover, this hyperconnected pattern was linked to oceanic boundlessness and unity, which indicates an important mapping between brain dynamics and subjective experience, pointing towards “egotropic effects” (vs hallucinergic) of the drug.

PhD candidate and co-author of the paper Larry Fort, University of Liège, emphasizes: “Psychedelic drugs like psilocybin are often referred to as hallucinogens both scientifically and colloquially. As such, we expected that the hallucinatory dimensions of experience would correlate the highest with psilocybin’s hyperconnected pattern. However, hallucinatory experience had a strong, but weaker correlation with this pattern than ego-modifying experiences. This led us to formulate the term ‘egotropic’ to draw attention to these ego-modifying effects as important, perhaps even more so than their hallucinogenic counterparts.”

Editor-in-Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Cameron S. Carter, MD, University of California Irvine, comments, “This study uses readily available resting state fMRI images acquired after psilocybin ingestion to provide new insights into the neurophysiological mechanisms underlying the subjective and clinical effects of the drug. It sets the stage for future studies using other psychedelic agents to examine whether the dynamic connectivity effects reflect a general mechanism for the therapeutic effects of these compounds.

Lead investigator Athena Demertzi, PhD, Physiology of Cognition, GIGA-CRC In Vivo Imaging Center, University of Liège, adds, "We were pleasantly surprised to learn that the brain pattern of hyperconnected regions was further characterized by lower global signal amplitude, which works as a proxy to heightened cortical arousal. So far, this is the first time that such approximation of arousal levels using fMRI was attempted in psychedelic research. This might be an important correlation as we move towards a full characterization of brain states under psychedelics."

She concludes, "Given the resurgence in research regarding the psychotherapeutic applications of psychedelic drugs, our results are pertinent to understanding how subjective experience under psychedelics influences beneficial clinical outcomes. Is the effect driven by ego-dissolution? By hallucinations? As such, our work exemplifies how the strong inter-relatedness between egotropic effects of moderate dose psilocybin and its hyperconnected brain pattern can inform clinical focus on specific aspects of phenomenology, such as ego-dissolutions. With this information, healthcare professionals may learn how to best engineer psychedelic therapy sessions to produce the best clinical outcomes."

 

 

 

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JOURNAL

Biological Psychiatry Cognitive Neuroscience and Neuroimaging

DOI

10.1016/j.bpsc.2024.04.001 

METHOD OF RESEARCH

Imaging analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Dynamic Functional Hyperconnectivity after Psilocybin Intake Is Primarily Associated with Oceanic Boundlessness

ARTICLE PUBLICATION DATE

6-Apr-2024

COI STATEMENT

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article. Cameron S. Carter, MD, is Chair of the Department of Psychiatry & Human Behavior at the University of California, Irvine School of Medicine. His disclosures of financial and conflicts of interests are available at http://www.biologicalpsychiatrycnni.org/bpsc-editorial-disclosures.

Moon Ships and Mardi Gras: Sun Ra and the Arkestra in the 1970s

BY RON JACOBS

 MAY 10, 2024
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I have been listening to the music of Sun Ra since the mid-1970s.  His Arkestra performed somewhere in Washington, DC right around that time.  I didn’t attend the show (I was broke), but a few friends did.  I believe it was at a church.  My friends who attended maintained a certain ecstatic energy for a few days.  One of them insisted Sun Ra and his music had released this ecstasy within every concertgoer.  Although I was skeptical, I understood what he meant when I finally did see Sun Ra and the Arkestra a couple years later.  A new release from the Jazz Detective label reminded me of those times.  Simply titled Sun Ra at the Showcase Live in Chicago 1976-1977, this recording comes awful damn close to unleashing that same ecstasy.

The first disc opens with birdlike melodies sung by flutes.  The melodies become questions.  Percussion and some winds grow louder.  To some it might be a challenge.  To me it’s an invitation.  Sun Ra and Hi Arkestra call it a New Beginning.  This is the listener’s intro to a brand new release from the late Sun Ra.  It was the listeners in the concert audience at Chicago’s Showcase Lounge in 1976 and 1977, too.  These sounds retreat as a percussive rhythm reminds one of a dance and drum circle that shifts into sounds not described by any conventional scale.  Music of the spheres.  As the music continues, I find myself focusing first on the horns then the organ, the percussion just moving it all along.

Dixieland gone mad and the madness of bebop.  Soundscapes unafraid (indeed, intended) to bend the human ear and mind.  Bending both in a manner heretofore hidden behind highways and houses lit by conformity and sold as freedom.  I ain’t buying.  I’m sticking with Sun Ra.  These two discs unbind the mind (Frank Zappa said that).  The production quality created by the master Zev Feldman in his studios somewhere between now and then elevates the songs and enchantments revealed in the Arkestra’s performance.  Ethereal yet solid, otherworldly and out of sight.  The next thing you know, you feel like dancing.

I’m not the first to wonder.  Was Sun Ra a being from another galaxy or is he an earthling?  If he was the former, what was his mission?  If he was an earthling what was his mission?  As far as I can tell, no matter what his origin story, his mission was to expand our minds.  Through music and performance, poetry and costume.  He remains an ultimate if not the ultimate psychedelic musician.  There’s calmness and chaos, cacophony and rhythm in his composition.  There’s melody and madness.  A church revival, a free jazz carnival, Mardi Gras dance party and Dixieland jam combined only begins to describe the festival that is a Sun Ra show.

Fifteen or so years ago I wrote an encyclopedia entry about Sun Ra.  While writing it, I was reminded of a show of his I attended sometime in the 1970s.  The details are foggy, but the impact remains.  This recording brought it all back.  What might seem to be random sounds become compositions that include catchy melodies that invite the listener to dance.  It’s not Motown, but it makes the foot tap and the body shake if you let it.  Then, the next thing you know you’re at a clinic on twentieth century “classical” music.  It could be Messaien or Hindemith, but it’s Sun Ra.  Like his contemporaries in the avant-garde jazz world, Sun Ra and his band reveal the music we haven’t taken the time to hear. Then the song chants arrive.  “Journey on the moon ship…..”

As the title suggests, these two shows took place in early November 1977 (Disc 1) and in February 1976 (Disc 2) at Joe Segal’s Jazz Showcase in Chicago.  Thanks to producer Zev Feldman and his team of collaborators that included Michael D. Anderson, Joe Lizzi and Matthew Lutthans in the transfer and remastering of Richard Wilkerosn’s original reel-to-reel recordings, an audience well beyond those who fit into the Showcase almost fifty years ago can experience Sun Ra and His Arkestra performing live at one of their peak periods.  As always, Feldman and the rest of his CD production team have created packaging as exquisite as the musical production it encloses.  Reminiscences of the performance and of Sun Ra himself fill out a booklet of photographs reproduced in a beautiful format befitting the musicians and the music.  This music transcends human life and its temporality.  It lifts us all into a place we might not deserve, but can certainly benefit from.

Ron Jacobs is the author of Daydream Sunset: Sixties Counterculture in the Seventies published by CounterPunch Books. He has a new book, titled Nowhere Land: Journeys Through a Broken Nation coming out in Spring 2024.   He lives in Vermont. He can be reached at: ronj1955@gmail.com

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Now available from Penn Nursing: innovative, online psychedelic course

Business Announcement

UNIVERSITY OF PENNSYLVANIA SCHOOL OF NURSING

PHILADELPHIA (May 6, 2024) – Penn Nursing is proud to launch a groundbreaking new online course – Educating Nurses in Psychedelic Assisted Therapy – via Open Canvas. This free comprehensive course is designed to prepare nursing professionals for the pioneering field of psychedelic assisted therapy (PAT), aligning with the latest advancements in mental health treatment and Penn Nursing's commitment to social justice in healthcare.

With this new modality of care on the horizon, the need for well-educated, compassionate nursing professionals who can navigate the complexities of PAT will be critical. Anticipating this forthcoming need, Penn Nursing has developed coursework and student learning outcomes  that not only equip nurses with the necessary knowledge and skills but also aligns with the American Association of Colleges of Nursing’s (AACN) The Essentials: Core Competencies for Professional Nursing Education.

Nurses are champions of social justice, and this course emphasizes the role of nurses in advocating for equitable access to PAT. It addresses the importance of dismantling healthcare disparities and ensuring that the therapeutic potential of psychedelics is accessible to all, particularly marginalized communities. Each lesson plan is supported by a wealth of resources, including detailed slides, reading lists, and supplementary materials, crafted by Penn Nursing faculty through extensive literature reviews and theoretical synthesis. These materials are also applicable for use by researchers, educators, and other healthcare providers interested in psychedelics.

"We are at a pivotal moment in the intersection of mental health care and social justice," said Penn Nursing Dean Antonia M. Villarruel. "This resource represents our commitment to leading in both areas, preparing our nurses to lead in cutting-edge science and practice, and advocating for safe, equitable and compassionate care."

The free "Educating Nurses in Psychedelic Assisted Therapy" course is now open for enrollment and ready to use via Open Canvas. It is suitable for current nursing professionals, students, and anyone interested in the intersection of nursing, mental health care, and psychedelics therapy. This work is part of a larger partnership between Penn Nursing & Columbia School of Social Work, which has been supported by the Joe & Sandy Samberg Foundation and the Steven & Alexandra Cohen Foundation.

“We are proud to have supported the creation of this innovative psychedelic education program. What began as an idea has grown in many ways, including this remarkable new resource, now accessible to all,” said Sandy Beeber Samberg (BSN ’94, MSN ’95). “Penn Nursing’s ability to transform ideas into impactful initiatives is truly inspiring.”

For more information and to enroll, visit our Penn Open Canvas page by clicking here.

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About the University of Pennsylvania School of Nursing

The University of Pennsylvania School of Nursing is one of the world’s leading schools of nursing. For the ninth year in a row, it is ranked the #1 nursing school in the world by QS University. For the third year in a row, our Bachelor of Science in Nursing (BSN) program is ranked # 1 in the 2024 U.S. News & World Report’s Best Colleges rankings. Penn Nursing is also consistently ranked highly in the U.S. News & World Report annual list of best graduate schools and is ranked as one of the top schools of nursing in funding from the National Institutes of Health. Penn Nursing prepares nurse scientists and nurse leaders to meet the health needs of a global society through innovation in research, education, and practice. Follow Penn Nursing on: Facebook, X, LinkedIn, YouTube, & Instagram.

 

In psychedelic therapy, clinician-patient bond may matter most

Study links relationship strength to reduced depression for up to 1 year

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Peer-Reviewed Publication

OHIO STATE UNIVERSITY

COLUMBUS, Ohio – Drug effects have dominated the national conversation about psychedelics for medical treatment, but a new study suggests that when it comes to reducing depression with psychedelic-assisted therapy, what matters most is a strong relationship between the therapist and study participant.

Researchers analyzed data from a 2021 clinical trial that found psilocybin (magic mushrooms) combined with psychotherapy in adults was effective at treating major depressive disorder.

Data included depression outcomes and participant reports about their experiences with the drugs and their connection with therapists. Results showed that the stronger the relationship between a participant and clinician – called a therapeutic alliance – the lower the depression scores were one year later.

“What persisted the most was the connection between the therapeutic alliance and long-term outcomes, which indicates the importance of a strong relationship,” said lead author Adam Levin, a psychiatry and behavioral health resident in The Ohio State University College of Medicine.

Past research has consistently found that as mental health treatments changed, a trusting relationship between clients and clinicians has remained key to better outcomes, said senior author Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education in The Ohio State University College of Social Work.

“This concept is not novel. What is novel is that very few people have explored this concept as part of psychedelic-assisted therapy,” Davis said. “This data suggests that psychedelic-assisted therapy relies heavily on the therapeutic alliance, just like any other treatment.”

The study was published recently in the journal PLOS ONE.

Twenty-four adults who participated in the trial received two doses of psilocybin and 11 hours of psychotherapy. Participants completed the therapeutic alliance questionnaire, assessing the strength of the therapist-participant relationship, three times: after eight hours of preparation therapy and one week after each psilocybin treatment.

Participants also completed questionnaires about any mystical and psychologically insightful experiences they had during the drug treatment sessions. Their depression symptoms were assessed one week, four weeks, and up to one year after the trial’s end.

The analysis showed that the overall alliance score increased over time and revealed a correlation between a higher alliance score and more acute mystical and/or psychologically insightful experiences from the drug treatment. Acute effects were linked to lower depression at the four-week point after treatment, but were not associated with better depression outcomes a year after the trial.

“The mystical experience, which is something that is most often reported as related to outcome, was not related to the depression scores at 12 months,” Davis said. “We’re not saying this means acute effects aren’t important – psychological insight was still predictive of improvement in the long term. But this does start to situate the importance and meaning of the therapeutic alliance alongside these more well-established effects that people talk about.”

That said, the analysis showed that a stronger relationship during the final therapy preparation session predicted a more mystical and psychologically insightful experience – which in turn was linked to further strengthening the therapeutic alliance.

“That’s why I think the relationship has been shown to be impactful in this analysis – because, really, the whole intervention is designed for us to establish the trust and rapport that’s needed for someone to go into an alternative consciousness safely,” Davis said.

Considering that psychedelics carry a stigma as Schedule I drugs under the Controlled Substances Act, efforts to minimize negative experiences in future studies of their therapeutic potential should be paramount – and therapy is critical to creating a supportive environment for patients, the authors said.

This study ideally will help clearly position psychedelics treatment as a psychotherapeutic intervention moving forward – rather than its primary purpose being administration of a drug, Levin said.

“This isn’t a case where we should try to fit psychedelics into the existing psychiatric paradigm – I think the paradigm should expand to include what we’re learning from psychedelics,” Levin said. “Our concern is that any effort to minimize therapeutic support could lead to safety concerns or adverse events. And what we showed in this study is evidence for the importance of the alliance in not just preventing those types of events, but also in optimizing therapeutic outcomes.”

This work was supported by the Center for Psychedelic and Consciousness Research, funded by the Steven & Alexandra Cohen Foundation, the RiverStyx Foundation and private donors. It was also supported by the Center for Psychedelic Drug Research and Education (CPDRE), funded by anonymous donors.

Additional co-authors are Rafaelle Lancelotta, Nathan Sepeda and Theodore Wagener of Ohio State, and Natalie Gukasyan, Sandeep Nayak, Frederick Barrett and Roland Griffiths of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, where Davis is an affiliate.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0300501 

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder