Ayahuasca prevents the reinstatement of cocaine-induced rewarding effects in C57Bl/6 mice.
Vítor Bruno, Lídia Emmanuela Wiazowski Spelta, Matheus Lujan Pereira, Fabiane Dörr, Beatriz Aparecida Passos Bismara Paranhos, Fabiana Pereira Santos, Mauricio Yonamine, Raphael Caio Tamborelli Garcia, Larissa Helena Torres, Roberto de Pasquale, Rosana Camarini, Tânia Marcourakis
Psychopharmacology October 31, 2025 DOI: 10.1007/s00213-025-06946-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57Bl/6 mice |
| Intervention | Ayahuasca |
| Dose | 2.5, 7.5, 12.5 and 15 mg DMT/kg |
| Topics | Addiction Ayahuasca |
| Keywords | Cocaine use disorder Conditioned place preference Psychedelics Rewarding |
| Key findings | Ayahuasca treatment prevented the reinstatement of cocaine-induced conditioned place preference in mice. |
Abstract
Ayahuasca is a brew containing the psychedelic compound N,N-dimethyltryptamine (DMT) and β-carbolines, traditionally consumed in indigenous rituals. Recent studies suggest its potential to reduce depression and anxiety and as an alternative for treating ethanol and tobacco use disorders. However, research on its impact on cocaine use disorder remains limited. To analyze the rewarding effects of ayahuasca and to evaluate its therapeutic application on the reinstatement of cocaine-induced conditioned place preference (CPP) in C57Bl/6 mice. First, we examined if ayahuasca (2.5, 7.5, 12.5 and 15 mg DMT/kg, gavage) could induce CPP. Next, using a choice-based CPP paradigm, we compared the rewarding effects of cocaine (10 mg/kg, i.p.) with a previously established rewarding dose of ayahuasca (15 mg DMT/kg). Finally, we employed a cocaine-induced reinstatement protocol to assess whether ayahuasca could prevent the reactivation of cocaine-associated contextual preference. Therefore, mice were conditioned with cocaine and subsequently treated with water or ayahuasca (12.5 or 15 mg DMT/kg). Following a cocaine challenge, reinstatement of cocaine-induced CPP was evaluated. Our findings showed that while ayahuasca induced rewarding effects with the higher dose tested, these were less pronounced than those of cocaine. Moreover, ayahuasca treatment effectively prevented the cocaine-induced CPP reinstatement. These findings support the therapeutic potential of ayahuasca in the context of cocaine use disorder.
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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Ayahuasca produced weaker rewarding effects than cocaine and prevented cocaine-induced reinstatement of conditioned place preference.
Synthesized
Comparable studies
Other preclinical and animal studies on ayahuasca for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Mice | 2015 | Experimental study | |
| Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol intake by rats and on cFos expression in brain areas relevant to drug addiction Wistar rats | 2019 | Animal experiment | |
| Ayahuasca blocks ethanol preference in an animal model of dependence and shows no acute toxicity Mice | 2021 | Preclinical study | |
| Phytochemical and Neuropharmacological Evaluation of Banisteriopsis caapi, Paullinia cupana, and Turnera diffusa for Potential Anti-Addiction Activity | 2026 | Computational and in vitro study | |
| Ayahuasca treatment reduces 50-kHz ultrasonic vocalizations and modifies mesocorticolimbic monoamine neurochemistry in rats. Adult male Wistar rats | 2026 | Randomized controlled trial |
Citations in the library
Cites 29
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression Journal of Clinical Psychopharmacology December 11, 2015
- Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Journal of Pharmacology and Experimental Therapeutics June 18, 2003
- Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Current Drug Abuse Reviews June 1, 2013
- Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology November 1, 2018
and 24 more in the library