The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Alcohol use disorder remains a prevalent psychiatric condition with limited treatment options and high relapse rates. Psychedelic-assisted therapy with psilocybin and LSD shows promise but requires lengthy therapist sessions. The short-acting psychedelic 5-MeO-DMT may offer advantages. This review suggests 5-MeO-DMT can induce mystical experiences and ego-dissolution while increasing psychological flexibility and mindfulness, potentially alleviating mood-related comorbidities that drive alcohol use through negative reinforcement. Preliminary evidence indicates 5-MeO-DMT modulates neural oscillations—increases in gamma linked to ego-dissolution, increases in theta linked to psychological flexibility, and increased coherence across frequencies that may reorganize executive control networks. Animal studies show neuroplasticity, anti-inflammatory effects, 5-HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5, with implications for alcohol use disorder and comorbid mood conditions.

Study at a glance

Abstract

Abstract Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic‐assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4–12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short‐acting psychedelic 5‐methoxy‐ N,N ‐dimethyltryptamine (5‐MeO‐DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5‐MeO‐DMT. Primarily, 5‐MeO‐DMT is able to induce mystical experiences and ego‐dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood‐related comorbidities consistent with the negative reinforcement and self‐medication paradigms. In addition, preliminary evidence indicates that 5‐MeO‐DMT modulates neural oscillations that might subserve ego‐dissolution (increases in gamma ), psychological flexibility and mindfulness (increases in theta ), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5‐MeO‐DMT is characterized by neuroplasticity, anti‐inflammation, 5‐HT 2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood‐related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action.