Newsgroups: alt.drugs From: email@example.com (H-Man) Subject: mdma article #8 Message-ID: <1993Jul4.firstname.lastname@example.org> Date: Sat, 3 Jul 1993 17:52:10 GMT JAMA(R) 1988; 259: 1649-1650 March 18, 1988 SECTION: LETTERS LENGTH: 751 words TITLE: The Complications of ' Ecstasy' (MDMA) AUTHOR: Karl Verebey, PhD, New York State Division of Substance Abuse, Brooklyn; Jamyl Alrazi, Psychiatric Diagnostic Laboratories of America, South Plainfield, NJ; Jerome H. Jaffe, MD, National Institute on Drug Abuse, Baltimore ED/SECT: Edited by Drummond Rennie, MD, Senior Contributing Editor; Sharon Iverson, Assistant Editor. TEXT: To the Editor. -- Drs Brown and Osterloh, [n1] in a recent letter in THE JOURNAL, reported a nearly fatal toxic reaction to 3,4-methylenedioxymethamphetamine ( MDMA) . The estimated dose of MDMA administered was 100 to 150 mg and the blood levels, measured at one and two hours after hospital admission, were 6500 and 7000 ng/mL, respectively. Before MDMA became a Schedule 1 drug on July 1, 1985, [n2] it was used in doses of 100 to 150 mg by some psychiatrists who claimed that it was effective as a psychotropic catalyst and a sensory disinhibitor; at these doses, no toxic effects were reported. (The experiment was performed on March 12, 1985, before the scheduling in MDMA and was carried out by one of us [J.A.] in partial requirement for the degree of Doctor of Physiology.) At that time, we carried out a controlled study of MDMA metabolism and disposition in a single patient. On the basis of that study, we believe that the dose used in the study by Drs Brown and Osterloh would have had to have been much higher to produce the reported blood levels of MDMA of 6500 to 7000 ng/mL. Study. -- A healthy 40-year-old man weighing 74 kg ingested a single 50-mg dose of MDMA. [n3] Blood samples were collected one through 24 hours after administration of the dose. Fractional urine samples were collected from zero to 72 hours. The samples were analyzed for MDMA and 3,4-methylenedioxyamphetamine (MDA) by gas chromatography/mass spectrometry. 3,4-Methylenedioxyamphetamine, the N-demethylated biotransformation product of MDMA, also was identified in the plasma and urine samples. Plasma levels and urinary excretion of MDMA and MDA are presented in the Table. In plasma, the MDMA level peaked at 105.6 ng/mL two hours after administration of the dose and declined monoexponentially to 5.1 ng/mL by 24 hours. Plasma Levels and Urinary Excretion of MDMA and MDA in Man After Administration of a Single 50-mg Oral Dose of MDMA [SEE ORIGINAL SOURCE] Unchanged level of MDMA was the major urinary excretion product. In 72 hours, a total of 36 mg (72%) of the 50-mg dose was recovered from the urine. The missing 28% of the dose may have been biotransformed into other metabolites. Comment. -- The plasma levels of MDMA of 6500 to 7000 ng/mL reported by Drs Brown and Osterloh were 60 to 70 times higher than the peak level seen in our study and indicate that their patient must have taken a much larger dose than 150 mg, a dose only three times more than that used in our study. It is more likely that the observed severe toxic effects in the report by Drs Brown and Osterloh represent an expected toxic reaction to an overdose rather than a hypersensitivity reaction to the then customary doses of MDMA. Since, to our knowledge, ours is the first report on blood levels of MDMA in man in which the dose is known, the blood level of MDMA found by Drs Brown and Osterloh cannot be compared with any previously reported MDMA blood level reference value. Recently, MDA was identified as a neurotoxic substance that selectively destroys serotonergic nerve terminals in rat brain. [n3,n4] The finding in our study that the biotransformation of MDMA in man results in the formation of MDA should be a warning for the future legal or illicit use of MDMA by man. REFERENCES: [n1.] Brown C, Osterloh J: Multiple severe complications from recreational ingestion of MDMA ('Ecstasy' ). JAMA 1987;258:780-781. [n2.] Seymore RB, Wesson DR, Smith DE (eds): MDMA: Proceedings of the conference. J Psychoactive Drugs 1986;18:278-378. [n3.] Ricaurte C, Bryan G, Strauss L, et al: Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals. Science 1985;229:986-988. [n4.] Battaglia G, Yeh SY, O'Hearn E, et al: 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetatmine destroy serotonin terminals in rat brain: Quantification of neurodegeneration by measurement of tritiated peroxylene labeled serotonin uptake sites. J Pharmacol Exp Ther 1987;242:911-916. In Reply. -- The data of Verebey et al are useful in interpreting the plasma concentrations of the MDMA measured in the patient we reported. The dose reported by the patient was certainly underestimated. The ratios of MDA/ MDMA concentrations were never more than 0.02. This also suggests an overdose when compared with the ratios in the data of Verebey et al. The major concern in our letter was to reinforce the warning of Dowling et al [n1] that severe consequences have resulted from the use of MDMA. This concern is heightened by (1) a recent report stating that 39% of students at one college campus had tried MDA [n2] and (2) the neurotoxic effect of the metabolite MDA cited by Verebey et al. John Osterloh, MD Christopher Brown, MD San Francisco General Hospital University of California, San Francisco [n1.] Dowling GP, McDonough ET, Bost RO: 'Eve' and ' Ecstasy' : A report of five deaths associated with the use of MDEA and MDMA. JAMA 1987;257:1615-1617. [n2.] Peroutka SJ: Incidence of recreational use of 3,4-methylenedimethoxymethamphetamine ( MDMA, 'Ecstasy' ) on an undergraduate campus. N Engl J Med 1987;317:1542-1543.