Effects of Ayahuasca on Ethanol-Conditioned Place Preference and ΔFosB Expression in the Nucleus Accumbens in Mice

Oral lyophilized ayahuasca, at doses equivalent to those used in traditional ceremonies, blocked the conditioned place preference (CPP) that mice normally develop for ethanol. In a CPP paradigm, mice pretreated with ayahuasca showed no preference for the ethanol-paired compartment (time difference within ±7 seconds), while controls showed a moderate preference (about +60 seconds). The effect was significant at all tested doses, and no differences were observed among ayahuasca groups. Ayahuasca was well tolerated at ceremony-equivalent doses, though the highest dose (5000 mg/kg) produced transient serotonergic-syndrome-like signs and locomotor deficits. ΔFosB expression in the nucleus accumbens did not differ among groups 24 hours after the post-test. The findings suggest ayahuasca may blunt ethanol-context preference, warranting replication with stronger reward baselines and additional molecular markers.

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Abstract

Abstract Background Ayahuasca, a psychoactive Amazonian preparation, is increasingly studied for substance-use disorders. Objectives Investigate whether oral lyophilised-ayahuasca attenuates ethanol-induced conditioned place preference (CPP) in mice and alters ΔFosB expression in nucleus accumbens (NAc). Methods Male Swiss mice received water or ayahuasca (130-1950 mg/kg, p.o.) 30 min before each of eight ethanol pairings (2g/kg i.p.) in a CPP paradigm. A separate cohort underwent acute toxicology (650–5000mg/kg) with behavioural-observation and rotarod. Alkaloids were quantified by LC-MS/MS. ΔFosB-immunoreactive nuclei were counted in NAc 24h after the CPP post-test. Results Alkaloids levels were within traditional ranges. High-dose ayahuasca(5000 mg/kg) produced transient-serotonergic-syndrome-like signs and rotarod locomotor-deficit; lower doses did not express toxicity. Ethanol produced a moderate-CPP in controls(ΔTime≈+60s), whereas ayahuasca-pretreatment abolished preference at all doses(ΔTime within±7s). One-way ANOVA on ΔTime showed a robust-Treatment effect(F(3,36)=8.83, p=0.00016); Tukey tests: control differed from each ayahuasca group (all p<0.05), with no differences among ayahuasca doses. ΔFosB density did not differ among groups(p>0.05). Conclusions Ayahuasca was well tolerated at ceremonies-equivalent doses and blocked ethanol-induced-CPP across all doses, while ΔFosB levels in NAc were unchanged at 24h. Limitations on the CPP baseline and ΔFosB results may limit sensitivity, generalisability and interpretation. Findings provide preliminary evidence that ayahuasca-pretreatment may blunt ethanol-context preference, reinforcing the need of replication with stronger reward baselines, naïve controls and complementary molecular markers.