Therapeutic Potential of Psychedelics in Treatment of Psychiatric Disorders, Part 2

Psychedelics are being studied as treatments for psychiatric disorders. The FDA has granted Breakthrough Therapy Designations for MDMA-assisted psychotherapy for PTSD and for psilocybin with psychotherapy for treatment-resistant depression and major depressive disorder. Clinical trials are also exploring psychedelics for eating disorders, cognitive impairment, and substance use disorders. This review covers evidence for psilocybin, LSD, MDMA, and ayahuasca. Open-label studies of psilocybin for obsessive-compulsive disorder, depression, and substance use disorders show promising results. Randomized controlled trials of psilocybin for depression and anxiety in advanced cancer found that high-dose psilocybin produced large decreases in depression and anxiety, increased quality of life, and decreased death anxiety, with about 80% of participants sustaining the response at 6-month follow-up.

Study at a glance

Abstract

P sychedelics have recently gained attention as compounds with therapeutic potential in the treatment of psychiatric disorders.The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designations for (±)-3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy in severe posttraumatic stress disorder (PTSD) (in 2017) and for the adjunctive use of psilocybin with psychotherapy in both treatment-resistant depression (TRD) (in 2018) and major depressive disorder (MDD) (in 2019).Additionally, a number of clinical trials with psychedelics are ongoing for other indications such as eating disorders, cognitive impairment, and substance use disorders (SUD).This article is the second in a 2-part series 1 on the psychopharmacology and therapeutic effects of psychedelics, and it provides a review of the evidence for use of psychedelics, with a focus on psilocybin, lysergic acid diethylamide (LSD), MDMA, and ayahuasca. PsilocybinThe efficacy of psilocybin has been examined in open-label studies of treatment-resistant obsessive-compulsive disorder, TRD, and SUD such as alcohol and tobacco use disorders with promising results. 2 Randomized controlled trials (RCTs) of psilocybin are limited to the treatment of depression and anxiety in advanced cancer.In a double-blind crossover design RCT, 12 patients with advanced cancer received a single dose of psilocybin (0.2 mg/kg) and niacin (placebo) in 2 experimental sessions.Psilocybin resulted in a nonsignificant trend toward improvements in mood from the first session to 6-month follow-up. 3 A larger crossover design RCT that included patients with advanced cancer (n = 51), randomized to receive high-dose psilocybin (22 mg or 30 mg/70 kg) and low-dose psilocybin (1 mg or 3 mg/70 kg) in 2 experimental sessions, found that high-dose psilocybin produced large decreases in clinicianand self-rated measures of depression and anxiety, increased quality of life, and decreased death-anxiety.This response was sustained at 6-month follow-up in about 80% of participants when the