The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action
This review (2024) examines the potential therapeutic mechanisms of action for alcoholism (AUD) treatment using 5-MeO-DMT. It highlights that 5-MeO-DMT can induce mystical experiences and ego-dissolution, leading to increased psychological flexibility and mindfulness, which may alleviate AUD symptoms. Additionally, preliminary evidence suggests that 5-MeO-DMT modulates neural oscillations and exhibits neuroplasticity and anti-inflammatory properties, indicating its potential clinical implications for AUD and related psychiatric comorbidities.
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-HT2A 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.
Research Summary of 'The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action'
Introduction
Alcohol use disorder (AUD) is described as a pattern of compulsive heavy drinking with loss of control despite negative consequences, and it is associated with neuroadaptations across basal ganglia, extended amygdala and prefrontal cortex that impair incentive salience, negative affect regulation and executive function. The authors note that AUD remains highly prevalent and costly, with modest efficacy of current pharmacological and psychosocial treatments, high relapse rates, and a widening treatment gap; few new medications have been approved in the past 20 years, motivating investigation of novel therapeutic approaches. This paper sets out to provide an initial synthesis of the extant literature on 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) as a candidate treatment for AUD, with a particular focus on putative therapeutic mechanisms. Tap and colleagues frame 5-MeO-DMT as a rapidly acting, short-duration classic psychedelic (typically 15–20 minutes after inhalation) that can occasion mystical experiences, ego-dissolution and increases in psychological flexibility and mindfulness, and they review human observational and clinical reports, neuroimaging studies, and preclinical work to identify mechanisms that could plausibly reduce AUD symptoms.
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Tap, S. C. (2024). 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, 29(4). https://doi.org/10.1111/adb.13386
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