Journal of Psychopharmacology
January 13, 2015
Michael P. Bogenschutz, Alyssa A. Forcehimes, Jessica Pommy et al.
1,164 citations
In a small proof-of-concept study, ten volunteers with alcohol dependence received one or two supervised doses of psilocybin alongside therapy. Abstinence did not increase during the first four weeks of treatment but increased significantly after psilocybin administration, with gains largely maintained up to 36 weeks. The intensity of effects during the first psilocybin session strongly predicted reduced drinking and craving and increased abstinence self-efficacy in the following weeks. No serious adverse events occurred. These preliminary findings support larger controlled trials to test efficacy and mechanisms.
Nature Medicine
June 1, 2021
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein et al.
965 citations
A phase 3 clinical trial tested MDMA-assisted therapy against placebo for severe PTSD. Participants received manualized therapy with either MDMA or placebo alongside preparatory and integrative sessions. At two months after the last session, the MDMA group showed a significantly greater reduction in PTSD symptoms (average 24.4-point drop on the CAPS-5 scale) compared to the placebo group (13.9-point drop), with a large effect size. Functional impairment also improved more with MDMA. No serious safety issues such as abuse potential, suicidality, or heart rhythm problems were observed. The findings suggest MDMA-assisted therapy is highly effective and safe for severe PTSD, including in people with common co-occurring conditions.
JAMA Psychiatry
August 24, 2022
Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt et al.
668 citations
Two doses of psilocybin, given alongside psychotherapy, substantially reduced heavy drinking in people with alcohol use disorder compared to an active placebo (diphenhydramine) plus psychotherapy. Over 32 weeks, heavy drinking days averaged 9.7% in the psilocybin group versus 23.6% in the placebo group—a mean difference of 13.9 percentage points. Daily alcohol consumption was also lower with psilocybin. No serious adverse events occurred in the psilocybin group. The findings support further research into psilocybin-assisted treatment for alcohol use disorder.
Nature Medicine
October 1, 2023
Jennifer Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
400 citations
In a phase 3 trial, MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in 104 participants with moderate to severe PTSD. The average decrease in PTSD symptom severity was 23.7 points with MDMA-assisted therapy versus 14.8 points with placebo, and functional disability improved by 3.3 versus 2.1 points. Participants were ethnoracially diverse, with 27% identifying as Hispanic/Latino and 34% as other than White. Severe side effects occurred in 9.4% of the MDMA group and 3.9% of the placebo group; no deaths or serious adverse events were reported. The treatment was generally well tolerated.
Frontiers in Pharmacology
April 3, 2018
Tara C. Malone, Sarah E. Mennenga, Jeffrey Guss et al.
128 citations
Cancer patients who receive psilocybin-assisted psychotherapy often have personalized experiences that extend beyond their diagnosis, centering on self-compassion, love, acceptance of death, and past trauma. In a double-blind trial, 29 patients with cancer-related anxiety and depression received either psilocybin or niacin with psychotherapy. Psilocybin produced rapid and lasting reductions in anxiety and depression. Detailed accounts of four participants show that while the content of each psilocybin session was unique, common themes emerged. The findings highlight how the subjective effects of psilocybin can address individual spiritual and psychological needs.
Frontiers in Pharmacology
February 20, 2018
Michael P. Bogenschutz, Samantha K. Podrebarac, Jessie H. Duane et al.
125 citations
After a 40-year pause, clinical research on classic hallucinogens for addiction has resumed. An ongoing double-blind placebo-controlled trial tests psilocybin-assisted treatment for alcohol use disorder, building on a small open-label feasibility study. Descriptive case studies of three participants illustrate treatment trajectories. Pivotal moments during psilocybin sessions are individualized, vivid, and memorable, often extending beyond the clinical problem. Participants experienced lasting shifts in self-perception, consciousness, and relationship with alcohol. Experiences of catharsis, forgiveness, self-compassion, and love were as salient as mystical content. Feelings of increased mindfulness, spaciousness, and control over choices and behavior were reported. The treatment elicits highly variable experiences that appear to meet individual needs.
Drug Testing and Analysis
January 1, 2012
Paulo César Ribeiro Barbosa, Suely Mizumoto, Michael P. Bogenschutz et al.
112 citations
Ayahuasca, a psychedelic brew traditionally used by Amazonian peoples, has spread to urban areas worldwide, raising concerns about potential health risks. A review of 15 studies from the PubMed database examined the emotional, cognitive, and physical health effects of ayahuasca use after acute effects subsided. The accumulated data suggest that ayahuasca use is safe and may even be beneficial under certain conditions. However, methodological bias in the reviewed studies may have contributed to the preponderance of beneficial effects and the few adverse effects reported. The data do not yet allow definitive conclusions about ayahuasca's effects on mental and physical health, but some studies point toward beneficial outcomes.
Frontiers in Pharmacology
February 21, 2018
Elizabeth M. Nielson, Darrick G. May, Alyssa A. Forcehimes et al.
111 citations
In an open-label pilot study of psilocybin-assisted treatment for alcohol dependence, researchers analyzed 17 debriefing sessions conducted the day after psilocybin medication sessions. Participants described key phenomena related to changes in their drinking behavior and the acute subjective effects of psilocybin. The findings illuminate change processes in patients' own words during clinical sessions, shedding light on potential therapeutic mechanisms and how participants express the effects of psilocybin. This study is unique in analyzing actual clinical sessions rather than interviews conducted separately from treatment.
Comprehensive Psychiatry
November 1, 2016
Paulo César Ribeiro Barbosa, Rick J. Strassman, Dartiu Xavier Da Silveira et al.
104 citations
Regular ritual use of hoasca (ayahuasca) within a Brazilian religious group in the United States is associated with lower depression and confusion, higher agreeableness and openness, better memory performance, and less recent alcohol use compared to matched controls. The study of 30 members of the União do Vegetal and 27 non-user controls found no adverse effects on neuropsychological function. Lifetime hoasca use correlated with fewer physical health role limitations and less heavy alcohol use, suggesting the religious use of this psychedelic brew may have positive effects on mood and substance use.
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein et al.
97 citations
A phase 3 clinical trial tested MDMA-assisted therapy for severe PTSD. In 90 participants randomized to receive either MDMA or placebo alongside therapy, those receiving MDMA showed a significantly larger reduction in PTSD symptoms, with an average decrease of 24.4 points on the CAPS-5 scale compared to 13.9 points in the placebo group. Functional impairment also improved more with MDMA. No serious safety issues like abuse potential or suicidality were observed. The treatment was effective even for patients with common co-occurring conditions such as depression or substance use history. The authors conclude MDMA-assisted therapy is a safe and highly effective treatment for severe PTSD.
Journal of Humanistic Psychology
October 16, 2016
Michael P. Bogenschutz, Alyssa A. Forcehimes
96 citations
Research into the clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades. Effective experimental and clinical use requires psychotherapeutic models tailored to the disorder and integrated with the drug's pharmacological effects. This paper provides an overview of the history of psychedelic-assisted treatment, reviews known therapeutic mechanisms, and considers the purposes of psychotherapy in research and clinical contexts. The authors describe a therapy model they developed for a trial of psilocybin-assisted treatment for alcoholism and discuss advantages and disadvantages of alternative models, emphasizing the need for research to determine the most effective approaches for established indications.
Frontiers in Psychiatry
April 24, 2018
Paulo César Ribeiro Barbosa, Luís Fernando Tófoli, Michael P. Bogenschutz et al.
95 citations
Members of the Brazilian União do Vegetal (UDV) who drink ayahuasca in ceremonies show lower rates of current alcohol and tobacco use disorders compared to the general Brazilian population, even though their lifetime use of these substances is higher. Among 1,947 UDV members aged 18 and older, those who attended more ceremonies in the previous year and had longer membership reported greater reductions in alcohol and tobacco problems. The findings suggest that regular ceremonial ayahuasca use, within a religious context, is associated with reduced substance misuse, particularly for adults over 24 years old.
Curr Top Behav Neurosci
January 1, 2018
Michael P. Bogenschutz, Stephen Ross
84 citations
This chapter reviews therapeutic uses of serotonergic hallucinogens like LSD and psilocybin, which act primarily on serotonin 2A receptors. After covering history and human use, it summarizes clinical data, including work on treating alcoholism and other addictions, using LSD and psilocybin to relieve death-related distress in advanced cancer patients, and limited data on mood and anxiety disorders. Safety of these drugs is well-established. Early-phase research from the 1950s to early 1970s strongly suggested clinically relevant effects, particularly for LSD in alcoholism, but was discontinued before firm conclusions. Recent trials have resumed, showing encouraging outcomes for existential distress in cancer and addictions, though not yet sufficient to establish efficacy. Mechanisms of persisting effects remain poorly understood.
Current Drug Abuse Reviews
June 1, 2013
Michael P. Bogenschutz
47 citations
Renewed interest in classic hallucinogens such as psilocybin and LSD for treating addictions is supported by a review of older and recent research. The article provides direct and indirect evidence for therapeutic effects, outlines unique design issues for clinical trials with these drugs, and discusses the current status and design considerations for future randomized trials.
Psychology of Addictive Behaviors
June 5, 2023
Gabrielle Agin-Liebes, Elizabeth M. Nielson, Michael Zingman et al.
42 citations
In a small qualitative study of the first randomized controlled trial of psilocybin-assisted psychotherapy for alcohol use disorder, participants reported that the treatment helped them process emotions tied to painful past events, fostered self-compassion, self-awareness, and feelings of interconnectedness. The acute drug sessions laid the groundwork for more self-compassionate regulation of negative affect. Participants also described newfound belonging and improved relationship quality. The findings suggest psilocybin increases the malleability of self-related processing, reduces shame and self-critical thoughts, improves affect regulation, and lowers alcohol cravings, indicating that integrating self-compassion training with psychedelic therapy may enhance AUD treatment outcomes.
Spirituality in Clinical Practice
September 1, 2021
Samantha K. Podrebarac, Kelley C. O’donnell, Sarah E. Mennenga et al.
38 citations
No Summary
Am J Psychiatry
January 1, 2024
Kelley C. O’donnell, Brian T Anderson, Frederick S. Barrett et al.
31 citations
This critical response addresses misinterpretations and omissions in a commentary by Goodwin and colleagues on psilocybin-assisted therapy, arguing that the commentary misrepresents existing evidence and overlooks key methodological issues. The authors contend that the commentary fails to adequately discuss safety concerns, including adverse events and the potential for psychological distress, and omits important data on long-term outcomes. They emphasize the need for rigorous, balanced evaluation of psilocybin-assisted therapy's risks and benefits, cautioning against overstating positive outcomes while underreporting negative findings. The response calls for more transparent reporting and careful interpretation of clinical trial results.
Scientific Reports
February 7, 2024
Broc A. Pagni, Petros Petridis, Samantha K. Podrebarac et al.
30 citations
In a small pilot study, patients with alcohol use disorder underwent functional magnetic resonance imaging before and after receiving either psilocybin or diphenhydramine. Psilocybin increased activity in the medial and lateral prefrontal cortex and left caudate, while decreasing activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. For negative emotional cues, psilocybin increased supramarginal gyrus activity; for positive cues, it increased right hippocampus activity and decreased left hippocampus activity. These brain changes suggest enhanced goal-directed action, improved emotional regulation, and diminished craving, but larger studies are needed to confirm the neural mechanisms of psilocybin-assisted therapy.
Contemporary Clinical Trials
December 1, 2022
Kelley C O'Donnell, Sarah E. Mennenga, Lindsey T. Owens et al.
24 citations
Classic psychedelics like psilocybin may help people change their behavior in substance use disorders. This paper describes the protocol for a multi-site, double-blind, randomized controlled trial that tested psilocybin-assisted psychotherapy in 96 alcohol-dependent volunteers. Participants received either psilocybin or an active placebo (diphenhydramine) during two dosing sessions, alongside a structured 12-week psychotherapy platform. The primary outcome was the proportion of heavy drinking days over 32 weeks after the first dose. Secondary outcomes included safety, abstinence, craving, and self-efficacy. The primary results are reported elsewhere; this paper focuses on the rationale and design decisions.
American Journal of Psychiatry
January 1, 2025
Noam Goldway, Snehal Bhatt, Stephen Ross et al.
23 citations
Psilocybin-assisted therapy (PAT) produced lasting changes in personality, indicating a normalization of abnormal personality trait expression in people with alcohol use disorder. The findings suggest that PAT may reduce impulsiveness, or that impulsive individuals may inherently respond better to the therapy. Further research is needed to clarify the mechanism.
JAMA Psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
The American Journal of Drug and Alcohol Abuse
August 24, 2016
Michael P. Bogenschutz
18 citations
A pilot study testing a treatment model that uses 2–3 doses of psilocybin for smoking cessation provides long-term outcome data. The results suggest the intervention may help maintain abstinence over an extended period, though the small sample size and lack of a control group limit the strength of the conclusions.
Journal of Psychedelic Studies
September 1, 2019
Kelley C. O’donnell, Sarah E. Mennenga, Michael P. Bogenschutz
15 citations
Designing rigorous clinical trials of psilocybin for major depressive disorder requires careful attention to participant selection, placebo control, blinding, dosing, non-pharmacological support, outcome measures, and safety. Transparent methods and analysis maximize the chance of obtaining meaningful, reproducible results and help gain broader scientific acceptance for psychedelic research.
Nature Medicine
February 6, 2026
Joshua S. Siegel, Conor Liston, Ginger E. Nicol et al.
10 citations
Classic psychedelics, acting at the serotonin 5-HT2A receptor, alter brain function and consciousness. Research converges on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. Evidence of therapeutic response across neuropsychiatric indications is reviewed, integrating mechanistic findings. Challenges include discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms and clinical evidence linking subjective experience to therapeutic response, risks of enhanced neuroplasticity, and questions about trial design, scalability, and regulatory approval. The growth of psychedelic science may compel a rethinking of the relationship between subjective experience and biological change in psychiatry.
Nature Mental Health
October 7, 2024
Petros Petridis, Jack Grinband, Gabrielle Agin-Liebes et al.
10 citations
Psilocybin-assisted psychotherapy (PAP) may treat a wider range of psychiatric symptoms in cancer patients than previously recognized. Pooled data from two phase II randomized placebo-controlled crossover trials involving 79 participants with cancer-related distress showed that PAP significantly improved anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion, and somatization. No lasting phobia, paranoia, or psychosis was induced. Improvements were consistent across both trials, suggesting PAP could serve as a comprehensive mental health treatment for this population.