577. CLINICAL EVIDENCE AND APPLICATIONS OF PSYCHEDELICS FOR MENTAL ILLNESSES

Psychedelics like LSD and psilocybin are being studied again as treatments for mental illnesses, with recent rigorous trials investigating their use for depression, terminal illness, addiction, obsessive-compulsive disorder, and post-traumatic stress disorder. Psilocybin, a serotonin 2A receptor agonist, has shown rapid and robust antidepressant effects when combined with psychological support, with benefits lasting several months to a year after one or two sessions. Australia has approved psilocybin for treatment-resistant depression. Neuroimaging studies suggest psilocybin modulates brain circuits involved in mood disorders. A clinical trial in Japan is examining ketamine and psilocybin for treatment-resistant depression.

Study at a glance

Abstract

Abstract Background Psychedelics have long been explored as potential treatments for mental illnesses. Since the mid-20th century, clinical trials of psychedelics such as LSD for depression and anxiety in terminally ill patients have been conducted. In the 21st century, revived and accelerated efforts to promote the proper use of psychedelics in the medical field have led to increasingly rigorous trials investigating their use for depression, terminal illness, addiction, obsessive-compulsive disorder, post-traumatic stress disorder, and other psychiatric disorders. Aims & Objectives This session aims to provide an integrated review of the clinical evidence for the use of psychedelics in mental illnesses and to assess their potential mechanisms of action. Method We will explore the evolving role of psychedelics in mental health treatment, with a special focus on psilocybin for depression. The review will emphasize clinical outcomes and insights from neuroimaging findings reported in recent clinical trials. Results The session will highlight recent clinical trials examining the efficacy and safety of psychedelics, with an emphasis on psilocybin, one of the most extensively studied classical psychedelics. As the active hallucinogenic component of magic mushrooms, psilocybin functions primarily as a serotonin 2A receptor agonist. Psilocybin has demonstrated rapid and robust antidepressant effects when administered with psychological support comprising pre-session preparation, in-session support, and post-session integration. These benefits have been observed to persist for several months to a year following one or two treatment sessions. Notably, Australia has pioneered regulatory approval for psilocybin in the treatment of treatment-resistant depression (TRD), marking a significant milestone in the acceptance of psychedelic therapies. In addition to clinical outcomes, our discussion will delve into the potential clinical and biological mechanisms underlying psilocybin’s effects, drawing on advanced neuroimaging studies that elucidate how it modulates brain circuits implicated in mood disorders. We will also present clinical and neuroimaging data from our clinical trial in Japan, which investigates ketamine and psilocybin as a treatment for TRD to explore the path to its appropriate clinical use. Discussion & Conclusions Through a detailed exploration of clinical outcomes and neuroimaging findings, our session aspires to offer a comprehensive perspective on integrating psychedelics into modern psychiatric practice and to pave the way for future innovations in mental health treatment.