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Efficacy and Safety of Psychoactive Tryptamines in Addiction: A Systematic Review

Pim B. van der Meer, Nout Schukking, Miranda G. Dik, Aumer van Reemst, Juan José Fuentes, Ad A. Kaptein, Jan W. Schoones, Sebastiaan O Verboeket, Marleen M. de Waal, Anna E. Goudriaan, Cornelis Kramers, Arnt Schellekens, Matthijs G. Bossong, Metten Somers, Albert Batalla

Psychedelic Medicine October 8, 2025 DOI: 10.1177/28314425251364182 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Peer reviewed
Sample size 176
Population Patients with alcohol use disorder
Interventions dipropyltryptamine diethyltryptamine
Duration Up to 26 weeks of follow-up
Topics Addiction Psilocybin
Keywords Tryptamines Hallucinogen Psychoactive drug Adverse effect Randomized controlled trial Clinical trial Abstinence Pharmacology Meta-analysis Psychoactive substance Cochrane library
Key findings Psychoactive tryptamines other than psilocybin and ibogaine showed limited evidence for effectiveness in treating alcohol use disorder, with abstinence rates ranging from 10% to 38% and no difference in severity of alcohol use compared to controls.

Abstract

Background: Psychedelics such as lysergic acid diethylamide (LSD) and psilocybin have shown a beneficial effect on substance use disorder (SUD) symptoms. In this systematic review, we aimed to assess the efficacy and safety of psychoactive tryptamines in patients with an SUD or non-substance-related disorder (i.e., gambling disorder) in order to provide a comprehensive overview of the available evidence and identify potential research gaps.

Methods: A systematic literature search was performed in eight different databases up to February 2024. Clinical trials were included that assessed the efficacy and safety of psychoactive tryptamines other than psilocybin and ibogaine. A quality assessment of the included trials was done based on the revised Cochrane risk-of-bias tools.

Results: A total of four clinical trials (three randomized controlled trials and one single-arm clinical trial; n = 176 patients) were included, all in patients with alcohol use disorder. Dipropyltryptamine and diethyltryptamine were the two investigated psychoactive tryptamines. Abstinence ranged from 10% (duration of follow-up unknown) to 38% at 26 weeks of follow-up, and severity of alcohol use did not differ between the psychoactive tryptamine group and the control groups. Adverse effects were not well reported in the trials.

Conclusion: Studies assessing the efficacy of psychoactive tryptamines other than psilocybin and ibogaine in addiction are scarce and show limited evidence for effectiveness in the treatment of addictive disorders.

Comparable studies

Other systematic reviews and meta-analyses on psilocybin for addiction, most cited first.

Study Year Design Participants
Therapeutic effect of psilocybin in addiction: A systematic review Patients with alcohol use disorder or tobacco use disorder 2023 Systematic review n = 151
Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders Patients with psychiatric disorders related to anxiety, depression, and substance use 2017 Systematic review n = 7
The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis. Patients treated with classical psychedelics 2025 Meta-analysis
Psychedelic‐assisted treatment for substance use disorder: A narrative systematic review Participants in studies of psychedelic-assisted treatment for alcohol, tobacco, and... 2025 Systematic review n = 2,035
Psychedelic Treatments for Substance Use Disorder and Substance Misuse: A Mixed Methods Systematic Review Adults with substance use disorder or substance misuse 2023 Systematic review

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