JAMA Psychiatry
September 4, 2024
Marianna Graziosi, Jared T. Hinkle, Sandeep M. Nayak et al.
126 citations
Classic psychedelics such as LSD and psilocybin are generally well tolerated in clinical or research settings, though serious adverse events do occur. In a systematic review and meta-analysis of 214 studies, serious adverse events were reported for no healthy participants and for about 4% of participants with preexisting neuropsychiatric disorders, including worsening depression, suicidal behavior, psychosis, and convulsive episodes. Nonserious adverse events requiring medical intervention, such as paranoia and headache, were rare. In contemporary research, no deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders were reported after high-dose psychedelic administration. However, the quality of adverse event monitoring and reporting varied significantly across studies.
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.
Frontiers in Psychology
March 28, 2022
Sandeep M. Nayak, Roland R. Griffiths
76 citations
Among people who reported a belief-changing psychedelic experience, attributions of consciousness to a wide range of entities increased substantially. Before and after the experience, ratings of consciousness rose for non-human primates (from 63% to 83%), quadrupeds (59% to 79%), insects (33% to 57%), fungi (21% to 56%), plants (26% to 61%), inanimate natural objects (8% to 26%), and inanimate manmade objects (3% to 15%). Higher mystical experience scores predicted larger increases. These changes persisted even years later, while beliefs in free will and superstition remained unchanged. The findings suggest psychedelic experiences can durably alter how people attribute consciousness to other beings and objects.
Journal of Psychopharmacology
June 8, 2023
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
60 citations
Psilocybin-containing mushrooms produce weaker drug effects in people taking SSRI or SNRI antidepressants, with a 47% probability of weaker-than-expected effects for SSRIs and 55% for SNRIs, compared to 29% for bupropion, a non-serotonergic antidepressant. This dampening effect persists for up to three months after discontinuing the antidepressant, based on retrospective survey data from over 2,000 reports. Removing responses involving fluoxetine, which has a long half-life, did not change the result. The findings suggest that serotonergic antidepressants may reduce psilocybin's effects both during use and for a period after stopping.
PLoS ONE
August 24, 2022
Mary M. Sweeney, Sandeep M. Nayak, Ethan Hurwitz et al.
60 citations
Psychedelic drug experiences and near-death or other non-ordinary experiences both change people's beliefs about death, but direct comparisons are rare. In a survey of 3,192 individuals who reported such experiences, those from non-drug causes (e.g., near-death) were more likely to involve unconsciousness, clinical death, or imminent danger. Both groups reported similar reductions in fear of death, high personal meaning, spiritual significance, and psychological insight. However, psychedelic participants scored higher on standardized measures of mystical and near-death features, while non-drug participants more often rated their experience as the single most meaningful of their lives. Among psychedelics, ayahuasca and DMT produced stronger positive enduring effects than psilocybin and LSD.
The International Journal of Neuropsychopharmacology
May 10, 2021
Natalie Gukasyan, David B. Yaden, Matthew W. Johnson et al.
56 citations
Psychedelic substances produce unusual changes in conscious experience, leading some to propose they offer unique insights into consciousness. However, psychedelics are unlikely to provide information relevant to the "hard problem of consciousness," which involves explaining how first-person experience emerges. Instead, they bear on multiple "easy problems of consciousness," involving relations between subjectivity, brain function, and behavior. This review discusses common meanings of "consciousness" regarding psychedelics and considers models of their effects on the brain linked to explanatory claims about consciousness. It calls for epistemic humility about psychedelic research's potential to explain the hard problem while noting ways psychedelics may advance study of specific aspects of consciousness.
Psychoactives
April 16, 2024
Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak et al.
26 citations
Psychedelic research has returned after a period of suppression, but media coverage now often overstates benefits as much as it once overstated risks. The actual evidence is more mixed than commonly portrayed, so conclusions about effectiveness remain preliminary. Poor communication may mislead patients and misinform policy. This article reviews studies on psychedelics for depression, noting that effect sizes for other depression treatments—cognitive behavioral therapy, mindfulness, SSRIs, and ketamine—have decreased over time as trials improved. The authors suggest the same may happen for psychedelics: larger, better-controlled trials will likely show smaller, more realistic benefits. Clear communication is essential to set public expectations and guide policy.
The Journal of Clinical Psychiatry
January 13, 2022
Richard J. Zeifman, Dengdeng Yu, Nikhita Singhal et al.
18 citations
A meta-analysis of 7 psychedelic therapy clinical trials found that, relative to baseline, psychedelic therapy was associated with large decreases in suicidality acutely (80–240 minutes) and at 1 day, 1–8 weeks, and 3–4 months (standardized mean differences ranging from −1.48 to −2.36). At 6 months, the effect was medium (SMD = −0.65). Reductions were significant at all time points except 7–8 weeks. Acute and post-acute elevations in suicidality were rare (6.5% and 3.0%, respectively). The authors note limitations including heterogeneous samples and interventions, and suggest that controlled trials specifically evaluating psychedelic therapy for suicidality may be warranted.
Clinical Pharmacology & Therapeutics
October 5, 2023
Robert H. Dworkin, Michael Mcdermott, Sandeep M. Nayak et al.
16 citations
Combining a classic psychedelic (e.g., psilocybin) with psychotherapy may produce benefits that are synergistic—greater than the sum of each treatment alone—but current trials have not tested this directly. Most studies pair the drug with some form of psychological support, yet providing full psychotherapy is more costly and harder to scale than basic harm-reduction support. Factorial designs, in which patients are randomly assigned to drug plus psychotherapy, drug alone, psychotherapy alone, or double placebo, can isolate the separate contributions of each component and detect true synergy. Such trials require large sample sizes but could determine whether the added expense of psychotherapy is worthwhile for improving outcomes in conditions like depression, anxiety, and chronic pain.
Psychedelic Medicine
October 28, 2022
Bruna Giribaldi, Sandeep M. Nayak, Bilal A. Bari et al.
15 citations
A Bayesian reanalysis of a trial comparing psilocybin (25 mg) to escitalopram (20 mg) over 6 weeks in 59 patients with major depressive disorder found that psilocybin outperformed escitalopram on three of four depression scales, though evidence was not uniformly clinically meaningful. Using skeptical priors that bias results toward zero, the analysis showed strong to extremely strong evidence favoring psilocybin on the BDI-1A, MADRS, and HAMD-17, while evidence on the primary outcome (QIDS SR-16) was indeterminate. For clinically meaningful superiority, evidence was moderate against it for the QIDS SR-16 but moderate to strong for the MADRS and HAMD-17. Psilocybin showed extremely strong evidence of noninferiority to escitalopram across all scales. The findings support further research on psilocybin's relative efficacy.
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.
Journal of Psychoactive Drugs
September 7, 2023
Marianna Graziosi, Manvir Singh, Sandeep M. Nayak et al.
10 citations
Reports of psychedelic experiences show both similarities and differences across cultural contexts, yet most current characterizations come from Western medical and naturalistic settings. This article reviews the history of diverse psychedelic use in non-Western settings and compares accounts of acute subjective effects within and beyond Western, educated, industrialized, rich, and democratic (WEIRD) contexts. It contrasts themes from direct testimony and psychometric measures including the mystical experiences questionnaire, five-dimensional altered states of consciousness scale, Survey of God Encounters, Survey of Entity Encounters, Challenging Experiences Questionnaire, and Inventory of Nonordinary Experiences. Recommendations are offered for future empirical research to quantify cross-cultural similarities and differences.
February 24, 2021
Sandeep M. Nayak, Natalie Gukasyan, Frederick S. Barrett et al.
10 citations
preprint
Classic psychedelics such as LSD or psilocybin may pose a significant seizure risk for people taking the mood stabilizer lithium. Analysis of online reports found that 47% of 62 accounts of combining lithium with a psychedelic involved seizures, and an additional 18% resulted in bad trips; 39% required medical attention. In contrast, none of 34 reports of the mood stabilizer lamotrigine combined with a psychedelic involved seizures, and most lamotrigine reports (65%) indicated no effect on the psychedelic experience. The authors provisionally conclude that psychedelic use with lithium carries a seizure risk, warranting further research.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Philosophical Perspectives on Psychedelic Psychiatry
September 13, 2024
David B. Yaden, Sandeep M. Nayak, Roland R. Griffiths
4 citations
The proportion of people who change their metaphysical beliefs after psychedelic experiences is not yet known precisely, but evidence suggests such changes can occur in some cases. This review examines the accruing evidence on the prevalence and magnitude of these belief changes and considers potential psychological mechanisms. It also briefly reviews relevant historical and contemporary philosophical work and describes clinical guidelines. Philosophically informed recommendations are offered for research and clinical contexts where psychedelic-induced metaphysical belief changes may arise.
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.
Nature Mental Health
May 1, 2026
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
2 citations
A living systematic review and meta-analysis of 15 randomized controlled trials (801 participants) found that psilocybin-assisted therapy substantially reduces depressive symptoms compared to control conditions, with a standardized mean difference of −0.90 (Hedges’ g). The analysis included 12 trials (585 participants) in the primary model. Many studies had small sample sizes or risk of bias. The review is maintained as a living resource with an open-data database and online dashboard that will be updated as new evidence emerges.
JAMA Psychiatry
December 6, 2023
David B. Yaden, Natalie Gukasyan, Sandeep M. Nayak
2 citations
No Summary
The Journal of Clinical Psychiatry
May 9, 2022
Richard J. Zeifman, Dengdeng Yu, Nikhita Singhal et al.
2 citations
correction
In a meta-analysis of patient-level data on psychedelics and suicidality, two serious adverse events occurred that the original study authors deemed unrelated to the drug. One participant in a very low-dose psilocybin condition (1 mg/70 kg) completed suicide 11 days after administration, having reported boredom and left the session early. Another participant attempted suicide about two months after an active psilocybin dose (21–25.2 mg/70 kg), following a partner's sudden death and subsequent methamphetamine and crack cocaine use, with a brief psychotic episode. These events highlight the need for close monitoring of all participants during and after psychedelic therapy trials.
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.
June 9, 2023
Sandeep M. Nayak, Sydney White, Samantha Hilbert et al.
1 citation
preprint
A longitudinal study of 657 people planning a psychedelic experience measured changes in beliefs about mind perception, metaphysical positions, and Atheist-Believer status before and after the experience. Replicating prior work, participants showed increased mind perception for living and non-living targets such as plants and animals. However, there was little to no change in metaphysical beliefs like dualism or in Atheist-Believer status. These results contrast with cross-sectional studies suggesting psychedelics alter non-naturalistic beliefs or religious identity, but they support the idea that psychedelics specifically affect how people perceive minds in various entities.
October 28, 2022
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
1 citation
preprint
Serotonergic antidepressants, such as SSRIs and SNRIs, weaken psilocybin's effects, while the non-serotonergic antidepressant bupropion has less of a dampening effect. In 595 reports of taking psilocybin with an antidepressant, the probability of weaker than expected effects was 0.48 for SSRIs, 0.56 for SNRIs, and 0.29 for bupropion. After discontinuing a serotonergic antidepressant, reduced psilocybin effects persisted for up to 3 months, with odds of reduced effects not significantly different from the first week until 3–6 months post-discontinuation. The findings suggest that serotonergic antidepressants diminish psilocybin's effects both concurrently and for months after stopping.
June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
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.
medRxiv Preprint Server
March 27, 2026
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey et al.
preprint
A living systematic review and meta-analysis of six randomized controlled trials with 286 participants found that MDMA-assisted therapy reduces PTSD symptoms more than control conditions (Hedges' g = -0.71). More dosing sessions and higher cumulative doses were linked to larger effects. MDMA also led to higher response (risk ratio 1.35) and remission (risk ratio 2.25) rates. Most studies had low risk of bias per Cochrane guidelines, though issues like expectancy and functional unblinding remain. The evidence was rated low certainty using GRADE, and the authors note more trials are needed.