Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy

Psilocybin, a tryptamine alkaloid found in Psilocybe mushrooms, is metabolized into the active compound psilocin, which produces psychoactive effects primarily by partially activating the 5HT2A receptor. Psilocin also binds to other receptor subtypes, though these actions are not fully understood. Clinical trials have tested psilocybin at hallucinogenic doses for addictive disorders, anxiety, and depression. This review assesses psilocybin and psilocin as potential neuropsychiatric treatments, weighing therapeutic benefits against potential harms. The authors conclude that careful evaluation of the number needed to harm versus the number needed to treat will determine clinical viability, and they call for a responsible path forward in this field.

Study at a glance

Abstract

Abstract Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.