Up-to-Date on clinical and preclinical studies of psilocybin therapy

Psilocybin, the hallucinogenic compound in magic mushrooms, shows rapid and lasting antidepressant effects in patients with treatment-resistant depression, with only transient mild side effects like headache and fatigue. The U.S. FDA designated it a breakthrough therapy for major depressive disorder and treatment-resistant depression. This review presents clinical and preclinical research on psilocybin's antidepressant effects, focusing on the role of serotonin 5-HT2A receptors, and discusses the potential and challenges of psilocybin therapy.

Study at a glance

Abstract

Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants. In 2016, Carhart-Harris and colleagues reported that psilocybin, the hallucinogenic compound derived from magic mushrooms, exhibits rapid and enduring antidepressant effects in patients with treatment-resistant depression. Subsequent clinical studies have found the therapeutic potential of psilocybin in MDD, depressive episode in bipolar disorder, anorexia, and drug addiction. In 2018 and 2019, the U.S. Food and Drug Administration designated psilocybin as a "breakthrough medicine" for treatment-resistant depression and MDD, respectively. Notably, the side effects of psilocybin are limited to transient and mild issues, such as headache and fatigue, suggesting its safety. In 2023, we published a review on the role of serotonin 5-HT2A receptors in the antidepressant effects of serotonergic psychedelics (Nihon Yakurigaku Zasshi, Volume 158, Issue 3, Page 229-232). Here, we present our study alongside the latest clinical and preclinical research on the antidepressant effects of psilocybin and provide an overview of the potential and issues related to psilocybin therapy.