OPEN Foundation

L. Berro

Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations


Rationale: Accumulating evidence suggests that ayahuasca, a hallucinogenic beverage used in traditional Amazonian communities for ritualistic and curative purposes, has been associated with reduced rates of substance use disorders. However, the brain mechanisms underlying the therapeutic effects of ayahuasca have not yet been fully elucidated.

Objectives: The aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate.

Methods: The rewarding properties of ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) were investigated using the conditioned place preference (CPP) model. Furthermore, we evaluated the effects of repeated treatment with ayahuasca on the reinstatement of methylphenidate-induced CPP. Fos expression was evaluated in different limbic structures (cingulate cortex-area 1, prelimbic cortex, infralimbic cortex, orbitofrontal cortex-lateral orbital area, nucleus accumbens core and shell, ventral tegmental area, dorsal striatum, and basolateral amygdala) upon each experimental phase.

Results: Both ayahuasca and methylphenidate induced CPP in mice. However, ayahuasca had limited effects on Fos expression, while methylphenidate altered Fos expression in several brain regions associated with the behavioral effects of drugs of abuse. Treatment with ayahuasca after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced CPP. Those behavioral effects were accompanied by changes in Fos expression patterns, with ayahuasca generally blocking the changes in Fos expression induced by conditioning with methylphenidate and/or reexposure to methylphenidate.

Conclusions: Our findings suggest that ayahuasca restored normal brain function in areas associated with the long-term expression of drug wanting/seeking in animals conditioned to methylphenidate.

Reis, H. S., Rodrigues, I., Anjos-Santos, A., Libarino-Santos, M., Serra, Y. A., Cata-Preta, E. G., Oliveira-Campos, D., Kisaki, N. D., Barros-Santos, T., Yokoyama, T. S., Cruz, F. C., Oliveira-Lima, A. J., Barbosa, P., Berro, L. F., & Marinho, E. (2020). Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations. Psychopharmacology, 237(11), 3269–3281.

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Sensitization to the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA).


The recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has well documented prosocial effects and is currently under clinical investigation as a treatment for patients with PTSD, autism, and other conditions. Early clinical trials have found that MDMA-assisted therapy may have robust long-lasting therapeutic effects, yet the mechanism by which acute treatments produce these long-term effects is unclear. Sensitization to certain behavioral drug effects is a common rodent model used to assess long-lasting neurobiological adaptations induced by acute drug treatments. Nine independent experiments were undertaken to investigate if and how mice sensitize to the prosocial effects of MDMA. When treated with 7.8 mg/kg MDMA and paired every other day for a week, MDMA-induced social interaction increased precipitously across treatment sessions. This previously unreported phenomenon was investigated and found to be heavily influenced by a social context and 5-HT2AR activation. Social sensitization did not appear to develop if mice were administered MDMA in isolation, and pretreatment with MDL100907, a selective 5-HT2AR antagonist, inhibited the development of social sensitization. However, when MDL100907 was administered to mice that had already been sensitized, it did not attenuate social interaction, suggesting that 5-HT2AR activity may be necessary for the development of social sensitization but not the expression of MDMA-induced social behavior. Additional investigation is warranted to further explore the phenomenon of social sensitization and to determine the underlying neurobiological mechanisms.
Curry, D. W., Berro, L. F., Belkoff, A. R., Sulima, A., Rice, K. C., & Howell, L. L. (2019). Sensitization to the prosocial effects of 3, 4-methylenedioxymethamphetamine (MDMA). Neuropharmacology151, 13-20.,
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Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca.


The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.
Ribeiro Barbosa, P. C., Tofoli, L. F., Bogenschutz, M. P., Hoy, R., Berro, L. F., Marinho, E. A., … & Winkelman, M. J. (2018). Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Frontiers in psychiatry9, 136., 10.3389/fpsyt.2018.00136
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30 April - Q&A with Rick Strassman