Behavioural Brain Research
August 23, 2021
Carolina Aparecida Faria Almeida, Antônio Alves Pereira-Júnior, Jéssica Gonçalves Rangel et al.
33 citations
Repeated ethanol administration to mice produced behavioral sensitization, a model of alcohol use disorder. Subsequent daily treatment with ayahuasca (1.76 mg/kg DMT) for eight days attenuated that sensitization. Ayahuasca also reduced the anxiety-like behavior triggered by ethanol withdrawal and prevented ethanol-induced changes in 5-HT1a receptor and prodynorphin levels in the hippocampus, while reducing ethanol's effects on the dynorphin/prodynorphin ratio in the striatum. The results suggest ayahuasca may modulate neuroplastic changes caused by ethanol.
International review of neurobiology
January 1, 2024
Eduardo A V Marinho, Yasmim A Serra, Alexandre J Oliveira-Lima et al.
6 citations
Psychedelics such as LSD and psilocybin have shown promise for treating alcohol use disorder by reducing drinking and promoting abstinence. Ayahuasca, an Amazonian brew containing β-carbolines and DMT, has also emerged as a potential treatment. Clinical studies, mostly retrospective, report significant decreases in alcohol use among ayahuasca users. Pre-clinical evidence indicates ayahuasca blocks abuse-related effects of alcohol. The chapter reviews clinical and pre-clinical evidence suggesting ayahuasca may be a promising new pharmacotherapy for alcohol use disorder and discusses potential mechanisms.
Journal of Psychopharmacology
September 22, 2025
Vítor Bruno, Martha López-canul, Brandon Richardson et al.
3 citations
Psilocybin, at a dose of 10 mg/kg administered every other day, does not produce conditioned place preference (CPP) in Sprague-Dawley rats, indicating a lack of rewarding or reinforcing effects under this regimen. During conditioning, psilocybin increased head twitching, wet-dog shaking, and defecation, while decreasing grooming, body licking, and rearing compared to vehicle. However, 48 hours after the final injection, no behavioral differences remained between groups. These findings suggest that psilocybin's acute behavioral effects are transient and that it does not induce reward-related learning in the CPP paradigm, though further research is needed to assess addiction liability across different protocols.
Neurotoxicity research
June 7, 2025
Felype Valentim Duarte Castelhano, Carolina Aparecida de Faria Almeida, Giulia de Assis Braz et al.
3 citations
Combining ketamine with ethanol triggers greater nerve cell death than either drug alone, acting through oxidative stress and two programmed-cell-death pathways. In human neuroblastoma cells, the lowest observed adverse-effect levels were 1 mM ketamine and 100 mM ethanol. After 48 hours, the combination produced a possible synergistic increase in late apoptotic cells. Glutathione levels fell within 6 hours, and glutathione-peroxidase activity rose in all groups. Only the combination increased glutathione reductase and glutathione S-transferase activities after 3 hours, along with elevated caspase-8 and Bax expression, signaling both extrinsic and intrinsic apoptosis. The findings suggest heightened neuronal damage risk from combined use, though limitations include enzyme-activity variability, reduced sample size for some markers, and use of an immortalized cell line.
Frontiers in Molecular Biosciences
February 18, 2026
Gabriella de Souza Gomes Ribeiro, Beatriz Aparecida Passos Bismara Paranhos, Fabiane Dörr et al.
1 citation
Even modest increases in DMT exposure from ayahuasca may intensify serotonergic effects in individuals taking SSRI antidepressants, suggesting a clinically relevant interaction. The study provides a mechanistic and quantitative framework for assessing interaction risks between ayahuasca alkaloids and SSRIs, supporting clinical decision-making and harm-reduction strategies where controlled drug-drug interaction studies are not feasible.
Future Pharmacology
June 23, 2026
Gabriella de Souza Gomes Ribeiro, Pieter Annaert, Frederico Severino Martins et al.
CYP2D6 genetic variants substantially alter the body's exposure to the psychedelic brew ayahuasca's active compounds, N,N-dimethyltryptamine (DMT) and harmine (HRM). Using physiologically based pharmacokinetic modeling, poor metabolizers showed 53.3% higher area under the curve (AUC) and 40.5% higher peak concentration (Cmax) for DMT, with similar but smaller increases for HRM; ultra-rapid metabolizers showed reduced exposure to both. These results indicate that CYP2D6 polymorphisms contribute to interindividual variability in ayahuasca pharmacokinetics, with potential clinical implications.
Archives of Toxicology
November 12, 2025
Gilles Salles, Carolina Aparecida de Faria Almeida, Isabella de Carvalho Alves et al.
Ayahuasca compounds N,N-dimethyltryptamine (DMT) and harmine (HRE), both alone and combined, partially protected human SH-SY5Y neuroblastoma cells from cocaine-induced toxicity. Cells exposed to cocaine with DMT and/or HRE showed increased viability compared to cocaine-only groups. Flow cytometry indicated partial to complete protection against apoptosis, and western blot revealed reduced expression of the apoptosis marker caspase-8 in co-treated cells. These findings suggest Ayahuasca-derived alkaloids merit further research for neuroprotection and treatment of substance use disorders.
Psychopharmacology
October 31, 2025
Vítor Bruno, Lídia Emmanuela Wiazowski Spelta, Matheus Lujan Pereira et al.
Ayahuasca, a brew containing DMT and β-carbolines used in indigenous rituals, has shown potential for treating substance use disorders. In C57Bl/6 mice, ayahuasca at a high dose (15 mg DMT/kg) induced rewarding effects, but these were weaker than those of cocaine. When mice were conditioned with cocaine and later treated with ayahuasca (12.5 or 15 mg DMT/kg), the brew prevented the reinstatement of cocaine-induced conditioned place preference after a cocaine challenge. The findings suggest ayahuasca may have therapeutic value for cocaine use disorder by reducing relapse to drug-seeking behavior.
The International Journal of Neuropsychopharmacology
August 1, 2025
Valeria Bruno, Bruce Richardson, Martha López-canul et al.
In adult male rats, a high dose of psilocybin (10 mg/kg) did not produce rewarding effects in the conditioned place preference (CPP) paradigm, as there was no significant difference in time spent in the drug-paired compartment versus the vehicle-paired compartment. Psilocybin increased head-twitching, dog-shaking, and defecation while decreasing grooming, body licking, and rearing during conditioning sessions. These behavioral differences disappeared 48 hours after the last injection, indicating no long-term changes. The findings suggest psilocybin lacks rewarding properties and does not cause physical dependence, supporting its safety profile and therapeutic potential.
Research Square
July 25, 2025
Vítor Bruno, Lídia Emmanuela Wiazowski Spelta, Matheus Lujan Pereira et al.
Ayahuasca, 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.