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.
Psilocybin, the psychoactive substance in magic mushrooms, shows fast-acting and long-lasting antidepressant effects in patients with major depressive disorder, including those resistant to conventional treatment. It is considered relatively harmless compared to ketamine and other similar substances. The FDA has designated psilocybin as a breakthrough therapy for major depressive disorder. Serotonergic psychedelics like psilocybin and lysergic acid diethylamide also show potential for treating depression, anxiety, and addiction. Pharmacologically, these drugs cause hallucinations by stimulating cortical serotonin 5-HT2A receptors, but whether this receptor is responsible for therapeutic effects remains unclear. This review summarizes clinical and pre-clinical studies on psychedelics for psychiatric disorders and discusses 5-HT2A as a potential therapeutic target.