The current state of ayahuasca research in animal models: A systematic review.

Abstract

The psychedelic brew ayahuasca is increasingly being investigated for its therapeutic potential. Animal models are essential to investigate the pharmacological effects of ayahuasca since they can control important factors influencing it, such as the set and setting. Review and summarise data available on ayahuasca research using animal models. We systematically searched five databases (PubMed, Web of Science, EMBASE, LILACS and PsycInfo) for peer-reviewed studies in English, Portuguese or Spanish published up to July 2022. The search strategy included ayahuasca- and animal model-related terms adapted from the SYRCLE search syntax. We identified 32 studies investigating ayahuasca effects on toxicological, behavioural and (neuro)biological parameters in rodents, primates and zebrafish. Toxicological results show that ayahuasca is safe at ceremonial-based doses but toxic at high doses. Behavioural results indicate an antidepressant effect and a potential to reduce the reward effects of ethanol and amphetamines, while the anxiety-related outcomes are yet inconclusive; also, ayahuasca can influence locomotor activity, highlighting the importance of controlling the analysis for locomotion when using tasks depending on it. Neurobiological results show that ayahuasca affects brain structures involved in memory, emotion and learning and that other neuropathways, besides the serotonergic action, are important in modulating its effects. Studies using animal models indicate that ayahuasca is toxicologically safe in ceremonial-comparable doses and indicates a therapeutic potential for depression and substance use disorder while not supporting an anxiolytic effect. Essential gaps in the ayahuasca field can still be sufficed using animal models.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

• State of the evidence: DMT for depression ↑Supports

  Ayahuasca was safe at ceremonial-comparable doses and showed antidepressant effects and reduced reward from ethanol and amphetamines in animal models, while anxiety outcomes were inconclusive.

  Synthesized October 22, 2026

Comparable studies

Other systematic reviews and meta-analyses on DMT for depression, most cited first.