Substance use disorder (SUD) affects millions globally, often impairing brain reward circuits and personal life. Treatments face challenges like limited availability and poor patient retention. A non-systematic review of studies published through December 2021 examined classic (LSD, DMT, psilocybin, mescaline) and non-classic (ibogaine, ketamine, MDMA, salvinorin A, THC) psychedelics for SUD. Results are inconclusive for LSD, DMT, mescaline, MDMA, and salvinorin A. Moderate evidence supports psilocybin and ketamine for alcohol use disorder, ketamine for opiate and alcohol withdrawal, and THC preparations for reducing withdrawal in cannabis and possibly opioid use disorder. Psychedelics appear more effective as adjunct therapy. More research is needed.
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.