Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders
Lea J. Mertens, Katrin H. Preller
Pharmacopsychiatry January 20, 2021 DOI: 10.1055/a-1341-1907 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Topics | LSD Psilocybin Addiction |
| Keywords | Hallucinogen Clinical trial Psychotherapist Mood disorders Clinical psychology |
| Citations | 63 |
| Key findings | Modern clinical trials show promising results for psychedelics in treating substance use disorders and depression, but most lack methodological rigor to allow firm conclusions on clinical efficacy. |
Abstract
Abstract Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and ayahuasca) in the treatment of different psychiatric conditions, including substance use and mood disorders. In this review article, we outline common pathological mechanisms of substance use disorders (SUD) and unipolar depression. Next, the current literature on the effects of psychedelics is summarized in order to generate hypotheses regarding their potential therapeutic mechanisms of action in treating these psychiatric conditions. Finally, we review and discuss clinical trials published since 2011 investigating the effects of psychedelics in SUD and depression. While results from those modern clinical trials are promising, most of them do not meet the methodological requirements to allow firm conclusions on the clinical efficacy of psychedelics. Larger, blinded, randomized controlled trials (RCT) with clearly defined patient groups and well-defined primary endpoints are needed. Additionally, the therapeutic mechanisms of classical psychedelics are currently unknown. This review presents hypotheses derived from preclinical and human studies that need to be tested in future trials to better understand the clinical potential of psychedelic substances in modern psychiatry.
Comparable studies
Other narrative reviews on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Study of a New Schizophrenomimetic Drug—Sernyl | 1959 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The Pharmacology of Lysergic Acid Diethylamide: A Review | 2008 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| ADVERSE REACTIONS TO PSYCHEDELIC DRUGS. A REVIEW OF THE LITERATURE | 1984 | Review |
Citations in the library
Cited by 56
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine February 1, 2023
- Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study Translational Psychiatry August 2, 2022
- Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology October 1, 2023
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
and 51 more in the library
Cites 67
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
and 62 more in the library