Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews

ABSTRACT

Introduction: Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects.

Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included.

Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open label, and only few were RCTs, and most had small sample sizes and a short duration. Single or few doses of these drugs seem to be well tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.

KEYWORDS:

• 5-HT_2A receptor
• anxiety disorders
• ayahuasca
• dimethyltryptamine
• lysergic acid diethylamide
• mood disorders
• psilocybin
• substance-use disorders

Declaration of interest

JC Bouso is the Scientific Director of ICEERS. ICEERS is a non-profit organization that promotes the scientific research of plant hallucinogens such as ayahuasca and ibogaine. RG dos Santos is a member of the ICEERS Advisory Board and is a Fellow of the Brazilian National Post-Doctorate Program (PNPD/CAPES). JEC Hallak receives a CNPq (Brazil) Productivity Fellowship Award.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.