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E. Caldas

Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol intake by rats and on cFos expression in brain areas relevant to drug addiction

February 6, 2022 / Ayahuasca, Neuroscience, Papers, Substance Use Disorder / Leave a Comment / By / , , , , ,

Abstract

Ayahuasca is a hallucinogenic infusion used in religious rituals that has serotoninergic properties and may be a potential therapeutic option for drug addiction. In this study, Wistar rats had intermittent access to ethanol for 8 weeks, receiving water (control), naltrexone (NTX, 2 mg/kg body weight [bw] intraperitoneally [i.p.]) or ayahuasca (Aya) at 0.5x, 1x, or 2x the ritual dose in the final 5 days. A naïve group had access only to water. Ethanol intake was estimated throughout the experiment, and cFos expression was evaluated in medial orbital cortex (MO), ventral orbital cortex (VO), lateral orbital cortex (LO), nucleus accumbens (NAc), and striatum. Treatment with either NTX or Aya (oral) did not decrease ethanol intake compared to the baseline level (5th to 7th week), but the NTX group intake was significantly lower than controls (p < 0.05). Ethanol significantly increased cFos expression in the MO region for control (p < 0.0001), NTX (p < 0.05), Aya1 (p < 0.001), and Aya2 (p < 0.0001) groups. This increase was also observed in the VO for the Aya1 group (p = 0.035), in the LO for the Aya2 group (p < 0.01), and in NAc for NTX and ayahuasca groups (p < 0.005). Furthermore, NTX and Aya0.5 treatment decreased cFos expression compared to controls in the MO region (p < 0.05 and p < 0.01, respectively), but only the ayahuasca group reached levels not significantly different from the naïve group. Studies using other protocols and dose regime are necessary to better investigate the impact of ayahuasca on alcohol intake by rats to support the observations in humans. Additionally, the role of ayahuasca in mediating cFos expression in other selected brain regions and its relationship with the serotoninergic/dopaminergic systems and drug addiction need further investigation.

Nolli, L. M., de Oliveira, D., Alves, S. S., von Zuben, M. V., Pic-Taylor, A., Mortari, M. R., & Caldas, E. D. (2020). Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol intake by rats and on cFos expression in brain areas relevant to drug addiction. Alcohol (Fayetteville, N.Y.), 84, 67–75. https://doi.org/10.1016/j.alcohol.2019.10.005

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Reproductive effects of the psychoactive beverage ayahuasca in male Wistar rats after chronic exposure

March 9, 2017 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , ,

Abstract

Ayahuasca is a psychoactive beverage used ancestrally by indigenous Amazonian tribes and, more recently, by Christian religions in Brazil and other countries. This study aimed to investigate the reproductive effects of this beverage in male Wistar rats after chronic exposure. The rats were treated by gavage every other day for 70 days at 0 (control), 1×, 2×, 4× and 8× the dose used in a religious ritual (12 animals per group), and animals euthanized on the 71st day. Compared to controls, there was a significant decrease in food consumption and body weight gain in rats from the 4× and 8× groups, and a significant increase in the brain and stomach relative weight at the 8× group. There was a significant increase in total serum testosterone, and a decrease in spermatic transit time and spermatic reserves in the epididymis caudae in the 4× group, but not in the highest dose group. No significant changes were found in the other reproductive endpoints (spermatozoid motility and morphology, total spermatozoid count and daily sperm production), and histology of testis and epididymis. This study identified a no-observed-adverse-effect-level for chronic and reproductive effects of ayahuasca in male Wistar rats at 2× the ritualistic dose, which corresponds in this study to 0.62 mg/kg bw N,N-dimethyltryptamine, 6.6 mg/kg bw harmine and 0.52 mg/kg bw harmaline. A potential toxic effect of ayahuasca in male rats was observed at the 4× dose, with a non-monotonic dose–response. Studies investigating the role of ayahuasca components in regulating testosterone levels are needed to better understand this action.

Santos, A. D. F. A., Vieira, A. L. S., Pic-Taylor, A., & Caldas, E. D. (2017). Reproductive effects of the psychoactive beverage ayahuasca in male Wistar rats after chronic exposure. Revista Brasileira de Farmacognosia. 10.1016/j.bjp.2017.01.006
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Genotoxic evaluations in Wistar rats of the hallucinogenic plant extract ayahuasca

January 1, 2016 / Ayahuasca, Neuroscience, Papers, Publications / By / , , , ,

Abstract

Ayahuasca, a psychoactive infusion, is a sacrament used by indigenous and non-indigenous communities in Brazil and other countries. This beverage has vaunted healing properties; however, its use in a therapeutic context still lacks preclinical data to certify its safety and effectiveness. This study evaluated the genotoxic, mutagenic and cytotoxic potential of ayahuasca in Wistar rats after a single oral dose. Rats of both sexes were randomly distributed into five experimental groups (n=10): negative control that received filtered water, positive control that received doxorubicin and treated groups that received ayahuasca at 1, 5 and 15 times the usual dose taken in human religious rituals. The rats were euthanized 30 hours after dosage. Genotoxicity was evaluated by flow cytometry, comet assay and micronucleus test. Renal, hepatic and pancreatic functions were evaluated by serum analysis. Ayahuasca showed low genotoxicity, with an increased frequency of micronuclei only at the highest exposure level, and a non-observed-adverse-effect-level established at 5X the dose, or 1.5 mg/kg bw N,N-dimethyltryptamine a major component of the infusion. No cytotoxic effects were observed in the tested conditions. Furthermore, hepatic, renal and pancreatic functions remained without significant changes for all treated groups.

Pic-Taylor, A., Junior, W. M., Souza-Filho, J., Grisolia, C. K., & Caldas, E. D. (2016). Genotoxic evaluations in Wistar rats of the hallucinogenic plant extract ayahuasca. International Journal of Phytomedicine, 8(2). http://dx.doi.org/10.5138/ijpm.v8i2.1828
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Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

June 3, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1 mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated.

Pic-Taylor, A., da Motta, L. G., de Morais, J. A., Junior, W. M., Santos, A. D. F. A., Campos, L. A., … & Caldas, E. D. (2015). Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behavioural processes. http://dx.doi.org/10.1016/j.beproc.2015.05.004
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