Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

Abstract

Better known as “ecstasy,” 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today’s teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the classical psychostimulants or hallucinogens and is one of the few compounds capable of reliably producing prosocial behavioral states. As a result, MDMA has captured the attention of recreational users, the media, artists, psychiatrists, and neuropharmacologists alike. Here, we detail the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss its history and why it is perhaps the most important compound for the future of psychedelic science—having the potential to either facilitate new psychedelic research initiatives, or to usher in a second Dark Age for the field.

Aromatic Bromination Abolishes the Psychomotor Features and Pro-social Responses of MDMA (“Ecstasy”) in Rats and Preserves Affinity for the Serotonin Transporter (SERT)

“…Moreover, because these effects were reported to be different compared to those expected for structurally related psychedelics (Nichols and Glennon, 1984), it was proposed that the unique behavioral effects of MDMA might be mediated through its actions at SERT (Rudnick and Wall, 1992). Indeed, more recent evidence further elaborated that the acute psychotropic effects elicited by MDMA could be explained by means of a presynaptic mechanism that involves a reversal of the direction of transport of 5-HT through SERT elicited by the drug acting as a substrate (Sitte and Freissmuth, 2010; Dunlap et al, 2018).…”

“…The results obtained in the present work agree with this assumption, as shown by the differences between MDMA and 2-Br-4,5-MDMA in key ecstasy-like behavioral paradigms. Regarding the latter, it should be noted that the behavioral characterization of ecstasy has been attempted in different animal models, producing heterogeneous results that depend on several factors, such as dosage regimen, animal species or administration routes (Sáez-Briones and Hernández, 2013; Dunlap et al, 2018). Nevertheless, and for the purpose of the present work, a behavioral profile of MDMA in rats after acute administration based on complete dose-effect curves under the same experimental conditions has been used to evaluate the influence of aromatic bromination (Quinteros-Muñoz et al, 2010).…”

Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics

“…Furthermore, MDMA has demonstrated great promise in the clinic for treating PTSD via a treatment paradigm that can best be described as pharmaceutical-enhanced psychotherapy. 9 The use of psychoplastogens to enhance fear extinction is gaining traction and in principle, the same strategy could be used to extinguish drug-cue memories. Perhaps, this is why psychedelic compounds such as DMT, ibogaine, and LSD have shown promise for treating substance use disorders.…”

Utilisation des psychédéliques en psychiatrie : lien avec les neurotrophines

“…Il semblerait que l'aptitude de la MDMA à favoriser l'extinction soit médiée par la sérotonine et les récepteurs 5-HT 2A , car leur inhibition limite son efficacité (Young et al, 2017). Les effets de cette drogue sur les neurotrophines ne sont pas clairement établis du fait de la variabilité des protocoles et des doses, d'autant plus que les fortes doses et/ou l'administration répétée sont neurotoxiques (Dunlap et al, 2018).…”