Importance: Obsessive-Compulsive Disorder (OCD) has a 2% global prevalence, but only about 50% of patients respond to conventional treatment, underscoring the need for additional effective interventions. Objective: To assess the feasibility, safety, and preliminary evidence for efficacy of repeated psilocybin administration in OCD patients who had previously attempted psychotherapy or...
Psilocybin is among the serotonergic psychedelics closest to potential FDA approval, with growing evidence of therapeutic benefit across psychiatric conditions. As clinical trials expand, systematic characterization of adverse events (AEs) remains essential. While transient hypertensive responses are well documented, hypotensive events such as neurocardiogenic syncope (NCS) are rarely reported....
Serotonergic psychedelics are being investigated in the treatment of various disorders and in the improvement of well-being. Evidence suggests that their subjective effects may play a role in long-term behavioral outcomes. The subjective effects are mediated by 5-HT2A receptor agonism, but the 5-HT1A receptor may also play a role in the subjective effects. This study elucidates the effects of...
This study presents a living systematic review and open-data meta-analytic database from 15 randomized controlled trials examining the effects of psilocybin treatment on depressive symptoms. Existing evidence suggests that psilocybin treatment alleviates depressive symptoms. Depression is a major cause of disability worldwide, motivating interest in psilocybin as a potential treatment. Here we...
Background Psilocybin has increasingly been studied as a therapeutic for psychiatric and neurologic conditions, yet comprehensive cardiovascular safety data are limited. Current trials often exclude individuals with blood pressure ≥140/90 mmHg, criteria established conservatively without robust empirical support.
Reliable documentation of the traditional use of serotonergic psychedelics has long been confined to the Americas. Prevailing narratives often overstate the global prevalence and uniformity of traditional psychedelic use, extrapolating from a limited set of well-documented cases. Here, we report evidence of psilocybin mushroom use among Basotho traditional healers and non-healers in Lesotho and...
3,4-methylenedioxymethamphetamine (MDMA) has emerged as a potential treatment for post-traumatic stress disorder (PTSD), generating considerable enthusiasm in the field. However, rapidly changing evidence in a fast-moving field can be challenging to integrate. Here, we present a living systematic review and open-data meta-analytic resource on MDMA treatment for PTSD. In this initial release,...
Over the past 15 years, psychedelic treatments have garnered substantial clinical interest, with psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) advancing to phase 3 trials for various psychiatric conditions. This state-of-the-art review examines the evidence for these treatments and their proposed mechanisms of action, and identifies key challenges in clinical translation. Psychedelic...
Psychedelics' characteristic acute subjective effects predict therapeutic benefits, such as decreases in depression and anxiety. Thus, optimizing treatment involves better understanding which factors shape subjective effects. Session facilitators, who support participants before, during, and after psychedelic administration sessions, form an important part of the setting of these experiences....
This review provides an overview of Roland R. Griffiths' history of research, and his mentoring and collaborating approach to science that contributed to his impact in behavioral and neuropsychopharmacology and psychedelic medicines development. The approach was to summarize studies in his major domains of research, including preclinical and clinical abuse liability assessment science, alcohol,...
Classic psychedelic studies involve interpersonal interactions with participants before, during, and after the acute effects of psychedelics. In the field of psychedelic research, there is currently a debate about whether this interpersonal interaction is most accurately considered "psychological support," "psychotherapy," or something else. Proponents of the psychological support label...
In clinical trials for mental health treatments, functional unmasking (unblinding) is a widespread challenge wherein participants become aware of their assigned treatment. Unmasking is especially concerning with psychedelics, due to the near unmistakable acute effects (the “trip”), resulting in uncertainty about whether outcomes following treatment reflect true therapeutic properties of the...
Psychedelic treatments are considered to involve unique treatment challenges relative to other psychiatric interventions, though these are typically not explored in detail within clinical trial reports. To determine the types of challenges that providers encounter while administering psychedelic drugs in research settings and to assess provider opinions on safeguards that may be pursued to...
As psychedelic clinical trials expand in scale and influence, foundational challenges in trial design have come into sharper focus. In this commentary, we examine three interrelated issues: 1) the failure of blinding in psychedelic trials, 2) the potential of alternate controls including dose-response designs as an empirical workaround, and 3) the persistent ambiguity surrounding psychosocial...
Abstract Importance Depression is a major cause of disability worldwide, motivating substantial interest in psilocybin as a potential treatment. Objective To conduct a systematic review and meta-analysis of psilocybin’s impact on depressive symptoms and provide a living open data resource. Data Sources PubMed, Embase, Scopus, Web of Science, and PsycINFO retrieved by a systematic search up to...
Psychedelic therapies are promising new treatment options in psychiatry. Including the use of physical touch as part of treatment is an area of debate. This study aimed to characterize the viewpoints of practitioners on the use of touch in psychedelic therapy. An anonymous survey was distributed via e-mail to the contacts listed on ClinicalTrials.gov for trials of psilocybin and lysergic acid...
As classic psychedelics' therapeutic potential is studied and their popularity continues to rise, it is important to establish their relative risks and benefits. Previous surveys have tended to use convenience sampling on social media, select participants who have had either extremely positive or negative effects, and have not compared the risk/benefit profile of psychedelics to other...
Research has demonstrated both risks and benefits to using psychedelics as a therapeutic intervention for a variety of mental health conditions. In recent years, the public discourse around psychedelic treatments has been largely positive and focused on benefits more than risks. We believe the field would benefit from more balanced attention to the risks as well as benefits of psychedelics...
The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. Despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of shame-related processes with psychedelic use. This prospective, longitudinal study involved sequential, automated, web-based surveys that...
Objective: To assess the viewpoints of psychedelic practitioners in research settings on approaches to psychological support for psychedelic treatments. Methods: An anonymous survey was distributed via email to contacts listed on ClinicalTrials.gov for clinical trials of psilocybin and LSD, personal contacts of authors, and through snowball sampling. The survey included Likert type, multiple...
Psilocybin (a psychoactive compound found in "magic mushrooms" or "shrooms") has been gaining increased attention in research and popular culture as a number of clinical and observational studies have demonstrated that it may have potential for improving mental wellbeing. Relatedly, there has been a substantial uptick in naturalistic (e.g., real-world, non-clinical) psilocybin use in the United...
Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for...
There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles...
Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression...
Abstract Background: Personality disorders (PDs) are characterized by impairments in psychological functioning for which pharmacologic treatments have demonstrated limited efficacy. Psychedelics may offer a possible PD treatment, given preliminary evidence for their potential long-term positive effects on psychological functioning. However, little is known about safety or potential therapeutic...