JAMA Psychiatry
November 4, 2020
Mary P Cosimano, Alan K. Davis, Frederick S. Barrett et al.
1,269 citations
Two doses of psilocybin (20 and 30 mg per 70 kg) combined with supportive psychotherapy produced large, rapid antidepressant effects in adults with major depressive disorder who were not taking other antidepressants. In a randomized waiting list-controlled trial with 24 completers, depression scores on the GRID-Hamilton scale dropped from a mean of 22.8 at baseline to 8.0 one week after the second session, compared with 23.8 at the same time point in the delayed-treatment group. Seventy-one percent of participants showed a clinically significant response at week 1, and 58% met remission criteria. Effects persisted through the four-week follow-up.
Journal of Psychopharmacology
February 1, 2022
Natalie Gukasyan, Alan K. Davis, Frederick S. Barrett et al.
419 citations
In patients with moderate to severe major depressive disorder, psilocybin-assisted therapy produced large and sustained decreases in depression severity through 12 months. Scores on the GRID-Hamilton Depression Rating Scale dropped substantially from baseline at 1, 3, 6, and 12 months (effect sizes of 2.3, 2.0, 2.6, and 2.4, respectively). At 12 months, 75% of participants showed a 50% or greater reduction in symptoms and 58% achieved remission. No serious adverse events linked to psilocybin occurred during long-term follow-up, and no participants used psilocybin outside the study. Ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted greater well-being at 12 months but did not predict depression improvement.
Drugs Education Prevention and Policy
December 10, 2020
Monnica T. Williams, Alan K. Davis, Yitong Xin et al.
100 citations
Psychedelics such as psilocybin, LSD, and MDMA may reduce symptoms of racial trauma among Black, Indigenous, and other people of color (BIPOC) after a racist experience. In a cross-sectional survey of 313 diverse BIPOC in the US and Canada, participants retrospectively reported mental health symptoms 30 days before and 30 days after using a psychedelic. Analysis showed significant decreases in traumatic stress, depression, anxiety, and stress following the experience. A strong positive relationship emerged between acute psychedelic effects (mystical-type, insight, and challenging experiences) and reductions in psychopathology, even after controlling for prior discrimination and time since the experience. The findings suggest psychedelics could lessen the negative impact of racial trauma, though further research on psychedelic-assisted therapy for race-based trauma is needed.
Frontiers in Psychiatry
September 19, 2023
Hillary Jackson, Sara So, Abigail Yaffe et al.
87 citations
A large prospective survey of adults planning to take psilocybin outside clinical settings found that, on average, participants reported lasting reductions in anxiety, depression, and alcohol misuse, along with improvements in cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and decreases in neuroticism and burnout after use. However, a minority reported persisting negative effects: 11% at 2–4 weeks and 7% at 2–3 months after use, including mood fluctuations and depressive symptoms. The study included 2,833 respondents at baseline, 1,182 at 2–4 weeks, and 657 at 2–3 months post-use. Participants were primarily college-educated White men in the United States, mean age 40, who used dried psilocybin mushrooms (mean dose 3.1 grams) for self-exploration.
Chronic Stress
August 12, 2020
Alan K. Davis, Lynnette A. Averill, Nathan D. Sepeda et al.
83 citations
Among U.S. Special Operations Forces Veterans who completed a psychedelic treatment program with ibogaine and 5-methoxy-N,N-dimethyltryptamine in Mexico between 2017 and 2019, retrospective reports showed very large reductions in suicidal ideation, cognitive impairment, PTSD symptoms, depression, and anxiety from 30 days before to 30 days after treatment, along with a large increase in psychological flexibility. Increased psychological flexibility was strongly linked to reduced cognitive impairment and mental health symptoms. Most participants rated the experience among the top five most personally meaningful, spiritually significant, and psychologically insightful experiences of their lives. The findings are preliminary due to the retrospective, self-report, non-randomized design.
Journal of Psychedelic Studies
December 27, 2019
Nathan D. Sepeda, John M. Clifton, Laura Y. Doyle et al.
23 citations
People who used inhaled synthetic 5-MeO-DMT in a structured, supportive setting reported significantly more intense mystical experiences and enduring positive effects—such as greater meaningfulness, spirituality, and well-being—and fewer challenging experiences than those who used it in a non-structured context. In the structured context group, 83% had a complete mystical experience compared to 54% in the non-structured group. The findings suggest that a safe and supportive environment enhances the positive acute and lasting outcomes of 5-MeO-DMT.
Psychedelic Medicine
May 16, 2025
Roland R. Griffiths, William A. Richards, Robert L. Jesse et al.
14 citations
In clergy from various world religions who had never used psychedelics, two supported psilocybin sessions (20 mg/70 kg, then 20 or 30 mg/70 kg) led to sustained positive changes in religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in non-religious attitudes, moods, and behavior, compared with a waitlist control group. At 16‑month follow‑up, 96% rated at least one experience among the top five most spiritually significant of their lives, 42% rated it the single most profound, and 79% reported positive effects on daily sense of the sacred. No serious adverse events occurred, though 46% rated an experience among the top five most psychologically challenging of their lives.
Journal of Psychoactive Drugs
February 7, 2025
Amy Lehrner, Heather Jackson, David S. Mathai et al.
11 citations
Among 679 adults using psilocybin in naturalistic settings, 68.2% reported acute feelings of shame or guilt during the experience, which were difficult to predict. The ability to constructively work through these feelings predicted wellbeing 2-4 weeks later. On average, psilocybin produced a small but significant decrease in trait shame maintained 2-3 months after use (Cohen's dz = 0.37), though trait shame increased in 29.8% of participants. The activation of self-conscious emotions with psychedelics warrants further attention as a challenging experience subcategory relevant to psychological outcomes, potentially creating a unique learning condition for shame-related memory reconsolidation.
Psychedelic Medicine
August 30, 2023
Samantha Hilbert, David S. Mathai, Nathan D. Sepeda et al.
10 citations
Dissociatives like dextromethorphan may have clinical applications when used in supportive settings similar to those in psychedelic research, which prioritize optimizing psychologically valuable drug experiences. The analysis suggests that such contexts could enhance therapeutic outcomes.
Journal of Psychedelic Studies
September 4, 2025
Alan K. Davis, Meghan DellaCrosse, Nathan D. Sepeda et al.
4 citations
Over a five-year follow-up period, psilocybin-assisted therapy produced significant and sustained reductions in depression for people with major depressive disorder. Among the 18 participants who completed the study, 67% remained in remission for at least five years after treatment. Anxiety and functional impairment also improved. Qualitative interviews revealed lasting positive changes in mindset, emotional health, and relationships, including enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported. These findings support the long-term efficacy and safety of psilocybin-assisted therapy for reducing depressive symptoms and improving mental health.
Journal of Psychoactive Drugs
September 12, 2024
Katinka Hooyer, Rachel Yehuda, Alan K. Davis et al.
4 citations
About half of U.S. military veterans surveyed reported using psychedelics, most often for healing or treatment (70%) and spiritual purposes (48%). The vast majority (85%) said they benefited from use. Veterans who used psychedelics indicated they would be more likely to use VA services, and they expressed greater interest in psychedelic therapy compared to non-users. However, some adverse outcomes were reported, suggesting that without proper preparation and support, psychedelics may carry risks. The findings point to a potential role for psychedelic-assisted approaches in veteran mental health care.
Journal of Psychoactive Drugs
July 14, 2023
Christopher Timmermann, Aki Nikolaidis, Alan K. Davis et al.
4 citations
Spanish translations of three questionnaires measuring acute psychedelic effects—the Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ)—showed good psychometric properties in a sample of 442 native Spanish speakers. Confirmatory factor analysis confirmed that the factor structures matched the original English versions, and this consistency held across subgroups who had used LSD or psilocybin. Construct validity was supported by positive associations between the PIQ and MEQ and between these measures and changes in cognitive fusion, alongside negative associations with changes in prosocial behaviors. Predictive validity was indicated by strong relationships between persisting effects and scores on the MEQ and PIQ. The Spanish versions can be reliably used in research with Spanish-speaking populations.
Psychiatry Research
February 13, 2026
Sean P. Goldy, Nathan D. Sepeda, Samantha Hilbert et al.
1 citation
Psilocybin has shown remarkable potential in reducing depressive symptoms, with a clinical trial involving 216 participants revealing a 60% reduction in these symptoms after treatment. In this randomized controlled trial, varying doses were administered, demonstrating significant improvements in mood and well-being. Additionally, participants reported lasting effects beyond the initial sessions, highlighting psilocybin's promise as a transformative medicine. These findings could reshape approaches in clinical psychology and pain management, offering new avenues for therapy and enhancing the understanding of psychedelics in mental health.
medRxiv Preprint Server
April 28, 2026
Sandeep M. Nayak, Nathan D. Sepeda, Matthew Nielsen Dick et al.
preprint
Psilocybin is being studied as a treatment for psychiatric and neurologic conditions, but there is limited comprehensive data on its cardiovascular safety. Current clinical trials typically exclude people with blood pressure of 140/90 mmHg or higher, a cutoff set conservatively without strong empirical evidence.
Religion Brain & Behavior
March 31, 2026
Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.
After administration of LSD, psilocybin, mescaline, or DMT, mystical oneness—the core of mystical experience—showed dose-sensitive strong correlations with luminous light and renewal, and a moderate-to-strong correlation with ego disintegration. These findings from 386 healthy participants across 15 studies support a broader, dynamic model of mystical experience, where mystical oneness unfolds with ego disintegration, renewal, and luminous light. The results offer insights for psychedelic-assisted therapy.
Drug and Alcohol Dependence
July 1, 2024
Alan K. Davis, Adam W. Levin, Rafael Lancelotta et al.
No Summary
October 14, 2023
David S. Mathai, Daniel E. Roberts, Sandeep M. Nayak et al.
preprint
A longitudinal study of 679 adults planning to use psilocybin in naturalistic settings found that while most users (89.7%) described the experience as positive, acute feelings of shame or guilt were commonly reported (68.2% of users) and difficult to predict. The ability to constructively work through these feelings predicted wellbeing 2-4 weeks after use. Psilocybin produced a small but significant average decrease in trait shame that lasted 2-3 months, but trait shame increased in a notable minority (29.8%) of participants. The activation of shame-related experiences with psychedelics may pose a unique learning condition for both therapeutic and detrimental forms of memory reconsolidation.