Ayahuasca and Its DMT- and β-carbolines – Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment

Abstract

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N-dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice.

Cessation and reduction in alcohol consumption and misuse after psychedelic use

“…These results highlight an important and potentially transdiagnostic therapeutic mechanism of psychedelic-assisted addiction treatment, which is also currently being studied in people who use cocaine (ClinicalTrials.gov Identifier: NCT02037126, 2014b). Based on current and previous findings including preclinical data (Cata-Preta et al, 2018; Godinho et al, 2017; Oliveira-Lima et al, 2015; Vargas-Perez et al, 2017), it seems plausible that serotonin 2A agonist psychedelics may possess some inherently anti-addictive properties, and that in humans, these may be mediated by overall intensity and/or mystical-type effects of the drug experience (Bogenschutz et al, 2015; Garcia-Romeu et al, 2015).…”

Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey

“…Preclinical data are further elucidating our understanding of psychedelics' biological mechanisms, with recent findings showing serotonergic psychedelics can promote structural and functional neural plasticity (98), and have potent antiinflammatory effects (99), which may be correlated with observed therapeutic benefits. Animal models suggest diverse anti-addictive properties of serotonergic psychedelics for alcohol (100,101) as well as other drugs of abuse. Ayahuasca has been shown to reduce amphetamine self-administration in adolescent rats and normalize amphetamine related locomotor behavior (102).…”

Stability Evaluation of DMT and Harmala Alkaloids in Ayahuasca Tea Samples

“…In this method, a wide dilution factor (1:5000) was used in Because of its unique characteristics, the interest in studying ayahuasca is continuously growing. More recently, concerning the global trend in psychedelic therapy research, the therapeutic potential of this plant preparation has been studied as an alternative in the treatment of addiction [9][10][11], depression [12][13][14][15][16], and other mental health disorders [17,18]. In this context, the quantification of ayahuasca's main alkaloids prior to its administration in animal or human studies is essential, as well as the knowledge of the tea's sample origin, storage, and transportation conditions.…”