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.
April 23, 2026
Eli Stark-Elster, Mamosebetsi Sethathi, B. van der Merwe et al.
Traditional use of serotonergic psychedelics has been reliably documented almost exclusively in the Americas, leading to overgeneralizations about their global prevalence. Through semi-structured interviews with 25 Basotho traditional healers and 8 non-healers in Lesotho and South Africa, 15 healers and 6 non-healers independently identified Psilocybe maluti, a recently described psilocybin-producing mushroom endemic to southern Africa. Reported uses include incorporation into a psychoactive initiation brew, treatment of physical, mental, and spiritual ailments, recreation, and magical protection. Unlike the large ritualized doses of Mesoamerican psilocybin use, Basotho healers apply small doses of P. maluti alongside other psychoactive plants, especially Boophone disticha. Multiple lines of evidence suggest these practices predate the mid-twentieth-century popularization of psilocybin, expanding the known geographic scope of traditional psilocybin use and revealing a distinct mode of psychedelic application.
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.
medRxiv Preprint Server
December 5, 2025
Gabriel Loewinger, Mats J. Stensrud, Sandeep M. Nayak et al.
preprint
Functional unmasking (unblinding) in clinical trials for mental health treatments, especially with psychedelics, can bias results because participants often know they received the active drug due to its unmistakable acute effects. This undermines confidence that outcomes reflect true therapeutic properties rather than placebo-like effects. A counterfactual conceptualization formalizes the shortcomings of existing solutions like dose-response and active controls, and shows how modern causal inference approaches can isolate effects free of this contamination. Feedback mechanisms between perceived benefits and expectancies can make traditional methods obscure or exaggerate therapeutic benefits. The proposal motivates trial designs and statistical methods to mitigate the impacts of functional unmasking.
medRxiv
August 16, 2025
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
preprint
Psilocybin-assisted therapy produces substantial reductions in depressive symptoms compared to control conditions, according to a systematic review and meta-analysis of 12 randomized controlled trials with 711 participants. The pooled effect size was large (Hedges' g = –0.91), and effects appeared rapidly and remained consistent over several weeks. However, many studies had small sample sizes or risk of bias, and waitlist-controlled or crossover designs contributed heterogeneity. The review provides a living open data resource that will be updated as new evidence emerges.
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.
Tasman’s Psychiatry
January 1, 2023
Sandeep M. Nayak, Matthew W. Johnson
Hallucinogens include a wide range of substances with different effects and risks. This chapter examines disorders caused or worsened by two classes: classic psychedelics like LSD and psilocybin, which work mainly through 5HT_2A receptors, and MDMA. It reviews evidence on adverse effects such as acute toxicity, abuse potential, persistent perceptual disturbances (Hallucinogen Persisting Perception Disorder), psychosis, and neurotoxicity.