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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, Maurı́cio Yonamine, Raphael Caio Tamborelli Garcia, Larissa Helena Torres, Roberto de Pasquale, Rosana Camarini, Tânia Marcourakis

Research Square July 25, 2025 preprint DOI: 10.21203/rs.3.rs-7140966/v1 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study
Population C57Bl/6 mice
Intervention Ayahuasca
Dose 2.5, 7.5, 12.5 and 15 mg DMT/kg
Topics Ayahuasca
Keywords Pharmacology
Key findings Ayahuasca treatment reduced cocaine-induced conditioned place preference reinstatement in mice, with its own rewarding effects being weaker than those of cocaine.

Abstract

Abstract Ayahuasca is a psychedelic brew used for centuries in religious rituals by indigenous cultures. 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. We investigated the effects of ayahuasca 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 the potential of ayahuasca to prevent the drug-associated contextual preference reactivation. 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 reduced cocaine-induced CPP reinstatement. These findings highlight the therapeutic value of ayahuasca in the context of cocaine use disorder.

Comparable studies

Other preclinical and animal studies on ayahuasca, most cited first.

Study Year Design Participants
Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Eight ayahuasca samples from Peru and several Banisteriopsis caapi cultivars 1984 Qualitative and quantitative chemical analysis with in vitro assay
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains 2017 In vitro experimental study
N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice 2020 In vitro and in vivo experimental study
Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat Female Wistar rats 2015 Observational cohort
Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Mice 2015 Experimental study

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