The current state of ayahuasca research in animal models: A systematic review.
Dimitri Daldegan-Bueno, Natalia Maria Simionato, Vanessa Manchim Favaro, Lucas Oliveira Maia
Progress in neuro-psychopharmacology & biological psychiatry July 13, 2023 DOI: 10.1016/j.pnpbp.2023.110738 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 32 |
| Population | Rodents, primates, and zebrafish |
| Topics | Addiction Anxiety Ayahuasca Depression DMT |
| Keywords | Addictive behaviour Animal model Toxicity test Ayahuasca psychedelic medicine Traditional medicine Mental health depression Substance abuse Dependency Animal testing Toxicology Clinical trials |
| Citations | 18 |
| Key findings | Ayahuasca is toxicologically safe at ceremonial-comparable doses and shows therapeutic potential for depression and substance use disorder, but not for anxiety. |
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.
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Animal studies indicate ayahuasca is safe at ceremonial-comparable doses and shows an antidepressant effect, while anxiety-related outcomes remain inconclusive.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on DMT for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review | 2021 | Systematic review | |
| Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Healthy volunteers or patients with major depressive disorder | 2025 | Systematic review | |
| Ayahuasca Therapy: Possible Reduction of Suicidal Ideation in Treatment-Resistant Depression - A Systematic Review. Patients with depressive disorders | 2026 | Systematic review | n = 5 |