Ayahuasca, a potentially rapid acting antidepressant: focus on safety and tolerability

ABSTRACT

Introduction

Ayahuasca is a psychedelic brew originally used by Amazonian indigenous groups and in religious rituals. Pre-clinical and observational studies have demonstrated its possible potential as an antidepressant, and open- and placebo-controlled clinical trials corroborated these results. For it to become an approved treatment for depression, its safety and tolerability need to be assessed and documented.

Areas covered

We have gathered data regarding the occurrence of adverse events (AEs) in all reported randomized, placebo-controlled trials with healthy and clinical populations involving ayahuasca administration (n = 108 ayahuasca administrations). We systematically categorized these results, recorded their prevalence, and discussed the possible mechanisms related to their emergence.

Expert opinion

There were no reports of serious AEs, indicating a relative safety of ayahuasca administration in controlled settings. Most common AEs included nausea, vomiting, headaches, and transient increases in cardiovascular measurements. Ayahuasca research is still in its infancy, especially concerning the absence of large and robust clinical trials to verify its antidepressant effects. Dose standardization, legal prohibition of the possession of its alkaloids and how traditional communities will be compensated if ayahuasca becomes an approved medicine are the biggest obstacles to overcome for its future use in the therapeutic context.

KEYWORDS:

• adverse events
• antidepressant
• ayahuasca
• safety

Article highlights

• Ayahuasca has shown preliminary potential as a rapid-acting antidepressant.

• There were no reports of serious adverse events (AEs) in any randomized, placebo-controlled clinical trials done with ayahuasca in healthy and clinical populations to date.

• Most common AEs related to ayahuasca administration include nausea, vomiting, headaches, and transient above nominal cardiovascular variables. Less prevalent but more significant AEs include anxiety, dysphoric reactions, confusion, and dissociation/depersonalization.

• There were no reports of the need for medical or pharmacological interventions and all reported AEs were transient and subsided spontaneously.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Additional information

Funding

GN Rossi received funding from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). JEC Hallak is recipient of CNPq 1A productivity fellowship. RG dos Santos is Fellow of the Programa Nacional de Pós-Doutorado, Brazil (PNPD/CAPES).