MDMA (3,4-Methylenedioxymethamphetamine, "Ecstasy")

Index

   Index ('round and 'round we go...) 
   Chemical Structure 
   Synonyms 
   Physical Properties 
   Scheduling 
   References 
      Review Articles 
      Neurotoxicity 
      Hyperthermic Reactions 
      Dental Implications 

Chemical Structure

    O   /\\  /\  NHCH3
   / \ /  \\/  \/
  /   ||   |    |
CH2   ||   |    |
  \   ||   |    CH3
   \ / \  //
    O   \//

C11H15NO2 

Synonyms

Common Chemical Name: 
   3,4-Methylenedioxymethamphetamine 
Common Chemical Abbreviation: 
   MDMA, N-Methyl-MDA 
Chemical Abstracts: 
   1,3-Benzodioxole-5-ethanamide, N,alpha-dimethyl- (Current) 
   phenethylamine, N,alpha-dimethyl-3,4-methylenedioxy- (Pre-1972) 
   Homopiperonylamine, N,alpha-Dimethyl- (Archaic) 

   [66142-89-0] S-MDMA (+) 
   [69558-32-3] S-MDMA (+) HCl 
   [81262-70-6] R-MDMA (-) 
   [69558-31-2] R-MDMA (-) HCl 
   [69610-10-2] MDMA (racemic) 
   [64057-70-1] MDMA HCl (racemic) 
         

DEA Drug Control Numbers: 

   7287: MDMA HCl (racemic)
   7405: MDMA
   7406: MDMA (racemic)

Edgewood Arsenel: 
   EA-1475 
Merck: 
   5646 (11th ed) 
All Chemical Names: 
   3,4-Methylenedioxymethamphetamine (common) 
   N-Methyl-3,4-methylenedioxyamphetamine (common) 
   N-Methyl-3,4-methylenedioxyphenylisopropylamine (common) 
   N-Methyl-1-(3,4-methylenedioxyphenyl)-2-propanamine 
   2-Methylamino-1-(3,4-methylenedioxyphenyl)-propane 
   N-Methyl-beta-(3,4-methylenedioxyphenyl)-isopropylamine 
   N,alpha-Dimethyl-beta-(3,4-methylenedioxyphenyl)-ethylamine 
   N,alpha-Dimethyl-3,4-methylenedioxyphenethylamine 
   N,alpha-Dimethylhomopiperonylamine 
   N,alpha-Dimethylbenzodioxole-5-ethanamide (common) 
All Chemical Abbreviations: 
   MDM, MDMA, N-Methyl-MDA 
Unofficial/Street Names: 
   Ecstasy, XTC, X, E, Adam, Vitamin E, Love Drug (properly should be used with MDA). 

Physical Properties

Melting Points: 
   155 deg C (freebase @ 20 mm/Hg) 
   110-120 deg C (freebase @ 0.4 mm/Hg) 
   147-148 to 158-159 deg C (anhydrous HCl) 
   soften 132 deg C, 135-139 deg C (1/4 hydrate HCl) 
   soften 92 deg C, 138-145 deg C (hemihydrate HCl) 
   soften 50 deg C, 90-132 deg C (3/4 hydrate HCl) 
   soften 80 deg C, 107-133 deg C (monohydrate HCl) 

   "It is apparent that with uncertain hydration, the melting point is not an acceptable criterion of identity or of purity." (Shulgin, Journal of Psychoactive Drugs, 1986) 

Index of Refraction: 
   nD19 = 1.5311 

Scheduling

US: 
   27 Jul 1984 -- Initial Schedule I proposal (49 FR 30210) 
   31 Dec 1984 -- Notice of scheduling hearings (49 FR 50732) 
   31 May 1985 -- Notice of invocation of ESA powers (50 FR 23118, 50 FR 28395) 
   01 Jul 1985 -- Emergency Schedule I Placement during hearings (by 50 FR 23118) 
   17 Jun 1986 -- Extension of Emergency Schedule I (51 FR 21911) 
   13 Nov 1986 -- Final ruling of Schedule I status (see 51 FR 36552 for docs) 
UK: 
   Class A Drug 

References

Review Articles

Shulgin-AT. "The Background and Chemistry of MDMA." Journal of Psychoactive Drugs. Vol 18(4):291-304. Oct-Dec 1986.

   Background on the chemistry, toxicology, pharmacology, psychopharmacology, legal history and popular opinion on MDMA. Very information dense. Much of the data on MDMA presented above
   was found in this article. 

Rattray-M. "Ecstasy: Towards an Understanding of the Biochemical Basis of the Actions of MDMA." Essays in Biochemistry. Vol 26:77-87. 1991. 

   This is a good and fairly comprehensive overview of MDMA's biochemical effects on the brain. It is readible for people who have some knowledge of receptors and chemical processes in the
   brain, and is not overly technical. It attempts to delineate what is known about MDMA pharmacology and what is speculated. It includes sections on the mechanism of action of the neurotoxicity
   of MDMA. 

Dal Cason-TA. "An Evaluation of the Potential for Clandestine Manufacture of 3,4-Methylenedioxyamphetamine (MDA) Analogs and Homologs." Journal of Forensic Sciences. Vol 35(3):675-697. May
1990.

   This is the article to read for anybody who is interested in the different methods of synthesizing methoxylated amphetamines. It is, however, a little bit on the technical side. It references articles
   for the following methods of synthesis:

   From MDP-2-P (3,4-Methylenedioxyphenylacetone): 
   1. Sodium cyanoborohydride
   2. Aluminum amalgam (in PiHKAL)
   3. Sodium borohydride 
   4. Raney Ni catalysis
   5a. Leukart reaction via N-formyl-MDA (in Psychedelic Chemistry)
   5b. Leukart reaction via N-methyl-N-formyl-MDA
   From safrole: 
   6. Bromopropane (HBr - in Secrets of Methamphetamine Manufacturing)
   7. Ritter reaction
   From 3,4-methylenedioxy-2-nitropropane (one in PiHKAL): 
   8a. via N-formyl-MDA
   8b. via N-acetyl-MDA
   From 3,4-methylnedioxycinnamic acid:
   9a. Schmidt reaction directly from the phenylpropionic acid
   9b. Curtis reaction directly from the phenylpropionyl chloride
   9c. Hofmann reaction from the phenylpropionamide
   It also mentions other, less attractive, methods like the preparation of alkylenedioxy bridges from dihydroxy compounds and gives references.

Buchanan-JF, Brown-CR. "'Designer Drugs': A problem in Clinical Toxicology." Medical Toxicology. Vol 3:1-17. 1988.

   Starts: "Contrary to the popular belief that 'designer drugs' are original creations, the majority... are 'borrowed' from legitimate pharmaceutical research." It then launches into an overview of the
   toxicology of: amphetamines, TMA, DOM, PMA, DOB, 2C-B, MDA, MDMA, MDE, Fentanyl, Meperidine, MPTP, PCP analogues and Methaqualone derivatives.

Neurotoxicity

McCann-UD, Ricaurte-GA. "Reinforcing Subjective Effects of (+/-)3,4-methylenedioxymethamphetamine ('Ecstasy') May Be Separable from its Neurotoxic Actions: Clinical Evidence." Journal of Clinical
Psychopharmacology. Vol 13(3):214-217. 3 Jun 1993.

   Presents 3 cases of people who had taken 20mg fluoxetine 1 hour to 30 minutes before taking MDMA, one of whom had also tried 40mg fluoxetine pre-treatment with no differences noted from
   taking 20mg fluoxetine prior to MDMA. Also presented one case of a patient taking MDMA while being chronically treated for depression with fluoxetine. The results from the patient being
   chronically treated don't look particularly good to me since it was a first MDMA experience and also was not isolated from other drugs (EtOH was consumed). The other case reports, however,
   do look favorable. They all noticed certain differences from the prior MDMA experiences they had had before, but there was no note of the differences interfering significantly with the
   empathogenic/entactogenic effects of MDMA. All three reported less problems with post-MDMA fatigue and malaise. There were some indications that fluoxetine might help to allieviate anxiety
   and some physical symptoms, although it seemed to tend to increase nausea.

Hyperthermic Reactions

Henry-JA, Jeffreys-KJ, Dawling-S. "Toxicity and deaths from 3,4-Methylenedioxymethamphetamine ('Ecstasy')." Lancet. Vol 340:384-387. 15 Aug 1992. 

   This is the paper which caught the mass-media's attention. It discusses the hyperthermia and also possible hepatotoxic reactions to MDMA, but is not terribly useful for ascertaining the actual
   cause and frequency of these effects. Naive readers should be forewarned that every possible risk, no matter how slight, has been dredged up. It is hypothesized that an ideosyncratic reaction
   along with high ambient air temperature is responsible for the hyperthermia. The possibility that the hepatotoxicity was due to an ideosyncratic toxic hepatitis was not ruled out. The info on
   road traffic accidents is best discarded as meaningless.

Ritto-DB, Ritto-D. "Complications of 'Ecstasy' misuse." [letter] Lancet. Vol 340:725-726. 19 Sep 1992.

   This isn't of much interest to anyone besides aenesthetists. It suggests that aenesthetists be attentive to the possibility that a patient has ingested MDMA if they become hyperthermic while under
   aenesthesia.

Ellis-SJ. "Complications of 'Ecstasy' misuse." [letter] Lancet. Vol 340:726. 19 Sep 1992

   Critisizes the 15 Aug 1992 Lancet article for its failure to estimate how dangerous MDMA is, for being "judgemental and scaremongering", for including meaningless data on accidents, and for
   presenting data which could not even be used to determine if MDMA was more dangerous than aspirin.

Larner-AJ. "Complications of 'Ecstasy' misuse." [letter] Lancet. Vol 340:726. 19 Sep 1992

   Raises the possibility that a genetic defect might be responsible for MDMA-related hyperpyrexia. Suggests: "Family studies of the inheritance of polymorphisms in ryr1, with the use of DNA
   markers, combined with standardised in-vitro muscle biopsy contracture tests" might be used to support/refute this hypothesis.

Tehan-B, Hardern-R, Bodenham-A. "Hyperthermia associated with 3,4-methylenedioxyethamphetamine ('Eve')." Anaesthesia. Vol 48:507-510. 1993.

   (NOTE: this reference is here for completion of the references on entactogens and hyperthermia.)

   A case of MDE hyperthermia is presented. "...caffiene and halothane contractive tests for malignant hyperthermia susceptibility were negative." This would tend to refute the notion that an
   ideosynratic reaction was responsible as strongly suggested by Larner in the Sep 19 1992 Lancet. Also notes that "active cooling measures alone failed to lower body temperature" which may
   imply that the notion that ambient temperature is critically involved in producing MDMA hyperthermia is wrong. Much discussion is given to the technical details of treating hyperthermic MDMA
   users.

Dental Implications

Duxbury-AJ. "Ecstasy -- Dental Implications." British Dental Journal. Vol 175(1):38. Jul 10 1993.

   Notes that the effects on the jaw muscles of MDMA causes users to chew gum, and that dehydration causes them to drink soft drinks. Suggests that they should be advised to chew sugarless gum
   and drink bottled water. Also notes that MDMA teeth grinding can result in erosion of enamel, and presents some considerations for dentists. Be forewarned that you will need a medical
   dictionary to read this article, along with a bullshit filter to eliminate the "worst case" medical (not dental) scenario which is presented.


April 14, 1994 | lamontg@u.washington.edu 
