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 DOI: 10.21203/rs.3.rs-7140966/v1 via OpenAlex
Summary
AI-generated from the abstractAyahuasca, a psychedelic brew used in indigenous rituals, reduced the reinstatement of cocaine-induced conditioned place preference in C57Bl/6 mice, suggesting potential for treating cocaine use disorder. While ayahuasca itself produced rewarding effects at the highest dose tested (15 mg DMT/kg), these were weaker than those of cocaine (10 mg/kg). Treatment with ayahuasca (12.5 or 15 mg DMT/kg) after cocaine conditioning and before a cocaine challenge effectively prevented the reactivation of drug-associated contextual preference. The findings indicate therapeutic value for ayahuasca in cocaine use disorder, though research in humans remains limited.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57Bl/6 mice |
| Topics | Ayahuasca |
| Keywords | Psychology Pharmacology Neuroscience |
| Key finding | 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.