MDMA is increasingly being studied for therapeutic applications, yet the prevalence and characteristics of post-acute negative effects remain debated. We aimed to characterize MDMA's post-acute negative effects, including prevalence and symptom profile among recreational users. Given preclinical work and limited human evidence suggesting that certain supplements and antidepressants may mitigate...
Psychedelics—psychoactive substances that have characteristic effects on perception, cognition and mood—are attracting renewed clinical and policy attention for their potential to treat a range of conditions. Various ethical tensions are present in psychedelic clinical trials due to several characteristics of psychedelics and the psychedelic experience, including acute alterations of...
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...
Psychedelics have emerged as promising pharmacological agents for treating a range of neuropsychiatric disorders. While preclinical studies have provided valuable insight into the neural mechanisms underlying their effects, systematic characterization of psychedelic effects on inherent spontaneous behaviors in animal models remains limited. In the current study, male and female Sprague-Dawley...
As jurisdictions across the U.S. consider enacting policies that facilitate access to psychedelics, they must determine how the desire to expand access to these substances should be weighed against the need to adequately protect safety. Oregon's psilocybin services program offers an important early case study of this balance in practice. Under the Psilocybin Services Act, adults over 21 are...
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....
A number of proposals across different fields have suggested incorporating "independent" actors into the research process as a way to manage potential bias. For example, in response to allegations of bias in psychedelic science, some have suggested the idea of independent auditors for adverse events, as well as the incorporation of independent researchers into the research teams of psychedelic...
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.
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....
We are grateful to those who commented on our Target Article on ethical exceptionalism around psychedelics (see Box 1 for a summary of our main points) and to Cohen and Marks (2025) for their compl...
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...
This Viewpoint discusses how to fill policy gaps surrounding the use of psychedelics to treat mental health and substance use conditions, should they be approved by the US Food and Drug Administration.
The potential for psilocybin, and other psychedelic drugs, to fulfil a much needed and potentially transformative class of psychiatric treatments has garnered significant attention. Consequently, there has been a great deal of interest and investment in accelerating its development and potential implementation in routine clinical practice. However, the expanding scope of scientific discovery,...
The current revival of interest in classic psychedelics and other psychoactives such as ketamine and MDMA, coupled with changes to their regulatory status in many jurisdictions, necessitates rigorous ethical guidelines both within and beyond clinical and scientific contexts. This paper examines crucial ethical, philosophical, and policy considerations needed to ensure psychedelic use across...
The potential use of psychedelic-assisted therapy for adolescents with mental illness has sparked both interest and concern. Modern psychedelic research has focused on adults, and adolescents younger than 18 years are typically excluded due to ethical and legal challenges. To explore whether adolescents have been included in 21st century psychedelic research, we conducted a scoping review of...
Classic psychedelics, such as psilocybin and LSD, evoke certain kinds of altered states of consciousness. Specific features of the experience, such as its allegedly ineffable nature, have been discussed as posing challenges to the informed consent process. A growing call for tailored informed consent documents (ICDs) in the psychedelic bioethics literature raises the question of how closely...
Background Recent years have seen renewed clinical interest in the therapeutic potential of classical psychedelics, such as psilocybin, LSD, DMT, and mescaline. While modern studies have focused on adult populations, adolescents under 18 are routinely excluded due to regulatory, legal, and ethical challenges. Although there exists observational data and historical studies from 1959 to 1974...
This article presents a taxonomy of altered states of consciousness, primarily based on their central phenomenological features. Following taxonomic principles and a modified Delphi methodology, a multidisciplinary, international group identified eight distinct phenomenological/behavioral states (some with subcategories): proto and transitional, delirium, minimal to no awareness, experiential...
Insight - a sudden change in understanding or perspective that feels true or reliable - is a common occurrence during psychedelic experiences, and often considered by clinicians and patients to be central to their therapeutic value. However, their occurrence and role has not been systematically assessed. We reviewed all peer-reviewed studies that published data on insight catalysed by a classic...
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...
Recent discussions about the methodological rigor of psychedelic clinical trials have focused on potential underreporting or misreporting of adverse events (AEs), with many calling for their systematic assessment to help mitigate these issues. In their recent paper, Palitsky et al. offer a comprehensive framework for the assessment of AEs in psychedelic-assisted therapies, with consideration of...