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

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.