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

Addiction Biology  – April 01, 2024

Source: OpenAlex

Summary

A compelling finding in Psychedelics and Drug Studies points to 5-MeO-DMT as a rapid-acting medicine for Alcohol use disorder. Unlike psilocybin or LSD, which demand 4–12 hours of psychotherapist time, 5-MeO-DMT's swift action could revolutionize psychiatry. Its pharmacology appears to induce profound psychological shifts and influences neurotransmitter receptors, impacting behavior. This action may alleviate AUD symptoms and mood comorbidities. In the broader context of drug studies, including Cannabis and Cannabinoid Research, this short-acting psychedelic offers a promising new direction for alcohol treatment.

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.

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