MDA is rarely sought as a recreational drug compared to other amphetamines; however, it remains widely used due to it being a primary metabolite,[2] the product of hepatic N-dealkylation,[3]ofMDMA (ecstasy). It is also a common adulterant of illicitly produced MDMA.[4][5]
MDA is bought, sold, and used as a recreational 'love drug', due to its enhancement of mood and empathy.[6] A recreational dose of MDA is sometimes cited as being between 100 and 160 mg.[7]
MDA can produce serotonergic neurotoxic effects in rodents,[8][9] thought to be activated by initial metabolism of MDA.[3] In addition, MDA activates a response of the neuroglia, though this subsides after use.[8]
In terms of the subjective and behavioral effects of MDA, it is thought that serotonin release is required for its empathogenic effects, dopamine release is required for its euphoriant (rewarding and addictive) effects, dopamine and norepinephrine release is required for its psychostimulant effects, and direct agonism of the serotonin 5-HT2A receptor is required for its mild psychedelic effects.[medical citation needed]
MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDA and major metabolites of MDMA, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.[27][28][29]
MDA was first synthesized by Carl Mannich and W. Jacobsohn in 1910.[20] It was first ingested in July 1930 by Gordon Alles who later licensed the drug to Smith, Kline & French.[30] MDA was first used in animal tests in 1939, and human trials began in 1941 in the exploration of possible therapies for Parkinson's disease. From 1949 to 1957, more than five hundred human subjects were given MDA in an investigation of its potential use as an antidepressant and/or anorecticbySmith, Kline & French. The United States Army also experimented with the drug, code named EA-1298, while working to develop a truth drug or incapacitating agent. Harold Blauer died in January 1953 after being intravenously injected, without his knowledge or consent, with 450 mg of the drug as part of Project MKUltra. MDA was patented as an ataracticbySmith, Kline & French in 1960, and as an anorectic under the trade name "Amphedoxamine" in 1961. MDA began to appear on the recreational drug scene around 1963 to 1964. It was then inexpensive and readily available as a research chemical from several scientific supply houses. Several researchers, including Claudio Naranjo and Richard Yensen, have explored MDA in the field of psychotherapy.[31][32]
MDA is schedule 9 prohibited substance under the Poisons Standards.[33] A schedule 9 substance is listed as a "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities."[33]
In 2010, the ability of MDA to invoke mystical experiences and alter vision in healthy volunteers was studied. The study concluded that MDA is a "potential tool to investigate mystical experiences and visual perception".[7]
A 2019 double-blind study administered both MDA and MDMA to healthy volunteers. The study found that MDA shared many properties with MDMA including entactogen and stimulant effects, but generally lasted longer and produced greater increases in psychedelic-like effects like complex imagery, synesthesia, and spiritual experiences.[34]
^ abde la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, et al. (April 2004). "Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition". Therapeutic Drug Monitoring. 26 (2): 137–144. doi:10.1097/00007691-200404000-00009. PMID15228154.
^Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA (August 1994). "Effect of the R(−) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors". Neuroscience Letters. 177 (1–2): 111–115. doi:10.1016/0304-3940(94)90057-4. PMID7824160. S2CID41352480.
^Noggle FT, DeRuiter J, Long MJ (1986). "Spectrophotometric and liquid chromatographic identification of 3,4-methylenedioxyphenylisopropylamine and its N-methyl and N-ethyl homologs". Journal of the Association of Official Analytical Chemists. 69 (4): 681–686. PMID2875058.
^Ho BT, McIsaac WM, An R, Tansey LW, Walker KE, Englert LF, Noel MB (January 1970). "Analogs of alpha-methylphenethylamine (amphetamine). I. Synthesis and pharmacological activity of some methoxy and/or methyl analogs". Journal of Medicinal Chemistry. 13 (1): 26–30. doi:10.1021/jm00295a007. PMID5412110.
^Butterick JR, Unrau AM (1974). "Reduction of β-nitrostyrene with sodium bis-(2-methoxyethoxy)-aluminium dihydride. A convenient route to substituted phenylisopropylamines". Journal of the Chemical Society, Chemical Communications. 8 (8): 307–308. doi:10.1039/C39740000307.
^Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA. Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30: 320–332, 2008.
^Naranjo C, Shulgin AT, Sargent T (1967). "Evaluation of 3,4-methylenedioxyamphetamine (MDA) as an adjunct to psychotherapy". Medicina et Pharmacologia Experimentalis. International Journal of Experimental Medicine. 17 (4): 359–364. doi:10.1159/000137100. PMID5631047.
^Yensen R, Di Leo FB, Rhead JC, Richards WA, Soskin RA, Turek B, Kurland AA (October 1976). "MDA-assisted psychotherapy with neurotic outpatients: a pilot study". The Journal of Nervous and Mental Disease. 163 (4): 233–245. doi:10.1097/00005053-197610000-00002. PMID972325. S2CID41155810.