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 via OpenAlex
Summary
AI-generated from the abstractA systematic review of clinical trials found limited evidence that psychoactive tryptamines other than psilocybin and ibogaine are effective for treating substance use disorders. Four trials involving 176 patients with alcohol use disorder tested dipropyltryptamine and diethyltryptamine. Abstinence rates ranged from 10% to 38% at 26 weeks of follow-up, and severity of alcohol use did not differ between the tryptamine and control groups. Adverse effects were poorly reported. The review concludes that studies are scarce and show limited evidence for effectiveness in treating addictive disorders.
Study at a glance
| 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 Medicine Psychiatry |
| Key finding | 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.