The Potential Therapeutic Effects of MEAI in the Treatment of Alcohol Use Disorder

Abstract

Purpose of Review: Alcohol use disorder (AUD) is a common and life-threatening disorder, but treatments remain limited, and relapse rates are high. Psychedelics have been studied as potential treatment options for AUD for nearly fifty years. Recently, 5-methoxy-2-aminoindan (MEAI) has emerged as a novel entactogen with potential therapeutic effects in AUD. This study compares the pharmacological profile of MEAI with three psychedelics previously suggested for the treatment of AUD: psilocybin, LSD, and MDMA. Recent Findings: A comprehensive literature review was conducted using Scopus, PubMed, and Web of Science for the pharmacology of psilocybin, LSD, MDMA, and MEAI. Additionally, relevant patents and preclinical studies on MEAI, and ongoing clinical trials were reviewed. Classic psychedelics exert their effects primarily through interaction with serotonin receptors, while MDMA and MEAI act mainly via neurotransmitter release, especially serotonin. Pharmacokinetically, psilocybin, LSD, and MDMA are extensively metabolized via UDP-glucuronyl transferase and CYPs and are primarily excreted via the kidneys, with MDMA exhibiting non-linear kinetics due to auto-inhibition of CYP2D6. MEAI appears to have a short half-life, variable oral bioavailability, and possible saturation of metabolizing enzymes in animals; however, the specific involved enzymes are unclear. Summary: Preliminary evidence suggests that MEAI may offer a therapeutic potential for AUD, treatment with milder subjective experience and less cardiovascular, neurotoxicity, and abuse potential compared to MDMA. Although anecdotal and laboratory reports suggest a safety profile comparable to the other three compounds, rigorous clinical studies are required to clarify safety and efficacy of MEAI in humans.