Psychedelics for mental health: a biochemical perspective

Psychedelics like psilocybin, mescaline, and LSD alter cognition and perception through the serotonin 5-HT2A receptor. Recent evidence shows they can produce lasting changes in neuroplasticity in preclinical models and are being tested for treating depression and anxiety. Key questions remain, including whether the hallucinogenic experience is necessary for therapeutic effects and how to design valid placebo controls. The authors conclude that the therapeutic potential is supported but more mechanistic preclinical studies are needed to establish causality.

Study at a glance

Abstract

Psychedelics, such as psilocybin, mescaline and lysergic acid diethylamide (LSD), are psychoactive substances that induce alterations in cognition, perception and sensory processing. Studies in rodent models and healthy human volunteers highlight the serotonin 5-HT2A receptor’s pivotal role in mediating hallucinogenic effects. More recent findings indicate that psychedelics induce lasting effects on neuroplasticity in preclinical models and are currently undergoing testing for their potential therapeutic effects on psychiatric conditions, including depression and anxiety. Critical questions persist, such as the necessity of the ‘trip’ for therapeutic benefits or the obstacles in establishing valid placebo groups in psychedelic studies. Despite challenges, this information supports the therapeutic potential of psychedelic compounds in addressing mental disorders. However, more direct and mechanistic based preclinical studies are required to assess the extent to which this association is causal.