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Empathogen psychoactive drugs or entactogens ̶ Recent research for clinical application

Empathogens or entactogens are a class of psychoactive drugs that produce experiences of emotional communion, oneness, relatedness, emotional openness, that is empathy or sympathy, as particularly observed and reported for experiences with 3, 4- methylenedioxymethamphetamine (MDMA). The term entactogen (Greek meaning, ‘’to touch within’’) was coined by Nichols (1986) to describe the psychactive effect of synthetic drugs 3, 4-methylendioxymetamphthamine (MDMA), 3, 4-methylendioxyamphthamine (MDA) and 3, 4-methylendioxy-N-ethyl-amphthamine (MDEA). Entactogens combine the catecholaminergic effects of methamphethamine, from which they are derived , with the serotogenic effect of psychodelics, exhibiting a unique profile of prosocial and interpersonal effects. Evidence for the distinction of entactogens from both methamphetamine and psychodelics come from studies of molecular structure activity relationhips and animal model of self-administration indicating the robustness of the drug family (Figure 1). The main focus of this presentation is MDMA, by far the most widely studied and recreationally used entactogens. This presentation provides a brief review of the history, proposed pharmacological mechanisms, safety issues, and clinical applications of the MDMA. Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic stress disorder (PTSD). Other potential therapeutic applications for MDMA therapy will be also described, including contemporary studies treating anxiety associated with autism and the ongoing study exploring the potential role for MDMA-assisted psychotherapy to treat alcohol use disorder. MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021. This means that if clinical efficacy criteria are achieved, MDMA would become a medicine. The results of our recent in silico study regarding ecotoxicity of entactogens and their metabolites will be also presented and dicused. Figure 1. Chemical structures of stimulant amphetamines, entactogens and phenylethylamine hallucinogens 1. Nichols DE. Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J Psychoactive Drugs. (1986) 18:305–313. doi: 10.1080/02791072.1986.10472362 ; 2. Gouzoulis-Mayfrank E. Differential Actions of an Entactogen Compared to a Stimulant and a Hallucinogen in Healthy Humans, In The Heffter Review of Psychodelic Reasearch, 2001, 2: 64-72 ; 3. Sessa B, Higbed L, Nutt D. A Review of 3, 4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy, Front. Psychiatry (2019) 10: 1-7, 10.3389/fpsyt.2019.00138 ; 4. A Phase 3 Program of MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder (PTSD), https://maps.org/research/mdma/ptsd/phase3, accessed March 2019 ;

Entactogens ; Psychoactive drugs ; Ecstasy (MDMA) ; Posttraumatic Stress Disorder (PTSD) ; ADMET ; Metabolism ; CYP45, Safety ; Ecotoxicity ; QSAR

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