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- Newsgroups: alt.drugs
- From: an13187@anon.penet.fi (H-Man)
- Subject: mdma article #8
- Message-ID: <1993Jul4.032713.25582@fuug.fi>
- 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.
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