This nonrandomized clinical trial assesses associations between psilocybin therapy and changes in systemic markers of inflammation and mitochondrial stress in people with Parkinson disease and mood dysfunction.
Serotonergic psychedelics are promising treatments for neuropsychiatric disorders, and their immunomodulatory effects may contribute to their clinical efficacy. However, we lack a systematic review and meta-analysis of these effects across in vitro, in vivo non-human, and human studies. We systematically searched PubMed, EMBASE, Web of Science, PsycINFO, LILACS and ClinicalTrials.gov for all...
Psychedelic drugs show promise in facilitating a variety of long-term psychological changes, but they may also lead to unexpected major life changes that have not been captured by measures typically used in clinical trials. The Psychedelic-related Major Life Changes Questionnaire ( P-MLCQ ) was created to assess psychedelic-related major life changes across 10 different domains and evaluated in...
Serotonergic psychedelics produce therapeutic effects in clinical trials of diverse neuropsychiatric disorders, and preclinical models of inflammatory, cardiometabolic, and neuropsychiatric diseases. These effects appear largely mediated by the serotonin 5-HT2A receptor (5-HT2AR). How could psychedelics elicit transdiagnostic therapeutic effects through a single receptor across tissues as...
The Five Dimensional Altered States of Consciousness (5D-ASC) Rating Scale is a self-report measure used to characterize changes in consciousness induced by pharmacological (e.g., psychedelics) and non-pharmacological methods (e.g., meditation), and predict clinical outcomes. Although it has been widely used with English-speaking participants, there is no version that has been adapted for...
3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative known as an "entactogen," influencing emotional and social processing. Phase III clinical trials of MDMA-assisted psychotherapy for post-traumatic stress disorder have reported promising results, and MDMA-assisted therapy is currently under regulatory review. However, the precise mechanisms underlying positive treatment...
September 7, 2025Mathew Herbert, Brian H. Blanco, Dimitri Perivoliotis et al.
preprint
There is promise for 3,4-Methylenedioxymethamphetamine (MDMA)-assistedpsychotherapy as a highly effective and durable treatment for posttraumatic stress disorder(PTSD). However, the Food and Drug Administration rejected MDMA-assisted psychotherapy inits current form, expressing concerns about the lack of standardization and empirical basis ofpsychotherapy methods. This highlights the need to...
Mood dysfunction is highly prevalent in Parkinson's disease (PD), a main predictor of functional decline, and difficult to treat-novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot...
A lack of diverse and representative participant samples in mental health intervention research perpetuates mental health disparities. This issue has become a salient concern in studies of psychedelic-assisted psychotherapy (PAT), which is emerging as a promising mental health intervention. This systematic review evaluates the reporting, representation, and analysis of participant...
Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been...
Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about...
Editorial on the Research Topic Down the rabbit hole -the psychological and neural mechanisms of psychedelic compounds and their use in treating mental health and medical conditions Psychedelic substances have demonstrated promising therapeutic effects across a wide range of mental health conditions including depression (1-13) anxiety disorders including generalized anxiety (14-16) and social...
Clinical trials using psilocybin therapy to treat anorexia nervosa (AN) are currently underway. The safety and tolerability of psilocybin is of utmost importance in individuals with AN who may present unique medical vulnerabilities. The purpose of this review is to describe how the common physiologic adverse effects of psilocybin may impact medical complications experienced by individuals with...
Balancing the need for effective treatments against the potential for serious adverse events in those undergoing psilocybin therapy with a family history of BD, we argue for caution in psychedelic clinical trials but not outright exclusion of these individuals. Our risk stratification tool allows for more nuanced inclusion and exclusion criteria.
Importance Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were...
Abstract Objective This study invited providers who care for patients with eating disorders to inform engagement, communication, and collaboration with psilocybin‐assisted psychotherapy interventions. Method Medical and mental health providers who treat patients with eating disorders were recruited via professional referral networks and participant driven sampling from across California to...
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with...
Ayahuasca is a psychedelic brew that has been the focus of an increasing number of investigations for its potential therapeutic effects. In addition to psychiatric improvements, qualitative studies and anecdotal reports suggest that ayahuasca use may influence gratitude and relationships with nature. Yet, to date, these specific changes have been understudied. Here, participants (N = 54)...
Psychedelic drugs are currently being investigated for their potential to facilitate a variety of long-lasting psychological changes. One area of psychological functioning that has yet to be systematically investigated in psychedelic research regards aesthetic experiences. This is surprising given the notable acute changes in perception induced by the drugs as well as the wealth of anecdotal...
Background: An emerging controversy in psychedelic therapy regards the appropriateness or necessity of psychedelic therapists having personal experience using psychedelics themselves. Although there are a number of potential advantages and disadvantages to personal use among psychedelic therapists, no studies to date have measured their use or other aspects of their training. Materials and...
RationalePsychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research.ObjectiveIn this article, we review the many methodological...
Posttraumatic stress disorder (PTSD) is a debilitating, chronic disorder and efficacy rates of current PTSD treatments are underwhelming. There is a critical need for innovative approaches. We provide an overview of trauma and PTSD and cite literature providing converging evidence of the therapeutic potential of psilocybin for PTSD. No study to date has investigated psilocybin or...
Growing evidence suggests that psilocybin, the active ingredient in hallucinogenic mushrooms, can rapidly and durably improve symptoms of depression, leading to recent breakthrough status designation by the FDA and legalization for mental health treatment in some jurisdictions. Depression in bipolar disorder is associated with significant morbidity and has few effective treatments. However,...
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with...
Abstract Objective: Given the treatment limitations of depression in bipolar disorder, we evaluated the known risks of using psilocybin (and similar substances) in this population, including a systematic assessment of published case histories, to assess the risk of psilocybin as a treatment of depression in bipolar disorder. Data Sources: A comprehensive search of case studies published through...