The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action
Summary & key facts
This paper is a first look at whether the fast-acting psychedelic 5‑MeO‑DMT might help people with alcohol use disorder. The authors reviewed existing studies in humans and animals and found early signs that 5‑MeO‑DMT can cause intense mystical feelings and a loss of self-boundaries, and that it changes brain rhythms and several biological systems. These effects might reduce drinking by improving mood, flexibility in thinking, mindfulness, emotion control, and impulse control, but the evidence is preliminary and more research is needed to know if it actually helps people.
- The paper is a review, meaning the authors looked over existing studies rather than running a new clinical trial.
- 5‑MeO‑DMT is much shorter acting than classic psychedelics like psilocybin and LSD, which often need many hours of therapist support. This short duration could make treatment cheaper and easier to deliver.
- In humans, 5‑MeO‑DMT has been reported to produce mystical-type experiences and a sense of ego-dissolution, which means people feel their usual sense of self loosen or disappear.
- Those psychological changes are linked in the paper to increases in psychological flexibility and mindfulness — ways of thinking that can help people cope with cravings and bad moods.
- Early brain studies suggest 5‑MeO‑DMT changes neural oscillations: it may raise gamma waves (linked to ego changes), raise theta waves (linked to flexibility and mindfulness), and increase coherence across frequencies (which could reorganize control networks).
- Animal studies show 5‑MeO‑DMT can promote neuroplasticity (the brain’s ability to change), reduce inflammation, activate the serotonin 2A receptor, and lower activity at a glutamate receptor called mGluR5. These changes could be relevant to addiction and mood problems.
- The authors say these effects could reduce alcohol problems by easing mood-related disorders that often drive drinking, based on ideas where people drink to self-medicate or to relieve negative feelings.
- The evidence is preliminary: most findings are early, come from animal work or small human studies, and the paper calls for more controlled research to test whether these mechanisms actually help people with alcohol problems.
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.