Ayahuasca, a psychedelic beverage, modulates neuroplasticity induced by ethanol in mice

Introduction

Alcohol use disorder (AUD) is a major public‑health problem with high morbidity and mortality and limited effective treatments; relapse rates exceed 50% and are higher when anxiety disorders co‑occur. Previous clinical and preclinical work has suggested that psychedelic substances, including ayahuasca (AYA), may have therapeutic effects in depression, anxiety and substance use disorders. Ayahuasca is a traditional Amazonian decoction combining Psychotria viridis leaves, which contain N,N‑dimethyltryptamine (DMT), and Banisteriopsis caapi vines, which provide β‑carbolines (harmine, harmaline, tetrahydroharmine) that inhibit monoamine oxidase A and permit oral DMT activity. Ethanol affects dopaminergic, serotonergic and opioid systems and produces neuroplastic adaptations; dynorphin (and its precursor prodynorphin) and κ‑opioid receptors have been implicated in anxiety, depression and addiction, and ethanol‑induced behavioural sensitization (EIBS) is a model of ethanol‑related neuroadaptation measured as progressively enhanced locomotor activation following repeated exposure. Almeida and colleagues set out to evaluate whether oral ayahuasca administration modifies ethanol‑induced behavioural sensitization and withdrawal‑related anxiety in mice, and whether AYA alters molecular markers in striatum and hippocampus related to dopamine (D1, D2), serotonin (5‑HT1a, 5‑HT2a) and the dynorphin/prodynorphin system. The study therefore combined behavioural testing (open field locomotion for sensitization and elevated plus maze for anxiety) with biochemical assays (UPLC‑ESI‑MS/MS quantification of AYA alkaloids and Western blotting of receptor and peptide levels) to probe potential neuroplastic effects of AYA on ethanol responses.