Review
doi: 10.1021/acschemneuro.8b00155. Epub 2018 Jul 12.Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine
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- PMID:30001118
- PMCID: PMC6197894
- DOI: 10.1021/acschemneuro.8b00155
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Review
Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine
Lee E Dunlap et al. ACS Chem Neurosci..
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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.
Keywords: 3,4-methylenedioxymethamphetamine; MDMA; empathogen; entactogen; psychedelic.
Figures
Structural relationships between MDMA and other psychoactive compounds. The common phenethylamine core is highlighted in red. Compounds are classified as psychostimulants, hallucinogens, or entactogens based on the behavioral responses they produce in experimental animals and their subjective effects in humans.
Common synthetic strategies used to produce racemic MDMA.
Synthetic strategies used to synthesize enantiopure MDMA. (A) Reductive amination using (S)-α-methylbenzylamine (B) Reductive amination using Ellman’s sulfinamide (C) Ring opening of an (S)-alanine-derived-aziridine.
Common metabolites of MDMA. CYP = cytochrome P450; COMT = catechol-O-methyltransferase.
Timeline of important events related to research on MDMA and classical psychedelics. Note the different peaks for research on MDMA and LSD. The data were obtained from a PubMed search for papers having titles that contained the search terms “3,4-methylenedioxymethamphetamine or MDMA” and “lysergic acid diethylamide or LSD” conducted on March 20, 2018.
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References
- Shulgin AT (1986) The background and chemistry of MDMA. J. Psychoactive Drugs. 18, 291–304. - PubMed
- Calculated using advanced chemistry development (ACD/Labs) Software V11.02 via SciFinder Scholar.
- Oberlender R, and Nichols DE, (1988) Drug discrimination studies with MDMA and amphetamine. Psychopharmacology (Berl) 95, 71–76. - PubMed
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