• Moritz Spangemacher, Lea J Mertens, Luca V Färber, Andrea Jungaberle, Henrik Jungaberle, and Gerhard Gründer.
• Dtsch Arztebl Int. 2024 Dec 27 (Forthcoming).

BackgroundTreatment with so-called psychedelic drugs, including psilocybin, lysergic acid diethylamide (LSD), and others, is among the most promising recent developments in psychiatry. This review focuses on psilocybin, a substance found in all mushrooms of the genus Psilocybe, because the largest amount of available evidence relates to this drug.MethodsThis review is based on pertinent publications (since 1969) that were retrieved by a selective search carried out in August 2024 in the PubMed and ScienceDirect databases employing the keywords "psilocybin" AND "long-term effects" AND "mental disorders", with an emphasis on randomized, controlled clinical trials (RCTs).ResultsThe available RCTs document the efficacy of psilocybin mainly against depression, including otherwise medically refratory depression. Most of the trials revealed a strong effect, with Cohen's d ranging from 0.67 to 2.6; they used a variety of depression scales and follow-up intervals. Evidence was also found for the efficacy of psilocybin against substance use disorders (alcohol in particular) and symptoms of anxiety accompanying life-threatening somatic illnesses, such as cancer. Initial uncontrolled studies have also shown significant improvement after the administration of psilocybin for other indications.ConclusionTreatment with psilocybin differs fundamentally from classic psychopharmacotherapy. Its potentially transdiagnostic, rapid, and sustainable efficacy and its positive effect on further dimensions of mental health beyond the patient's symptoms and psychopathology imply that it may have disease-modifying and salutogenic mechanisms of action. Psychotherapy accompanied by the administration of psychedelic drugs may turn out to be the first disease-modifying treatment in the history of psychiatry.

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