E is for Ecstasy by Nicholas Saunders

Appendix 4: Bibliography

Anon: Analog, Australian Forensic Drug Analysis Bulletin 12 14 (1990).

Two deaths associated with a plane crash, were analysed. There was MDMA present (blood, 1.4 and 1.7 mg/L; liver, 1.5 and 6.9 mg/kg; stomach, 0.24 and 0.55 mg; urine, 48 amd 44 mg/L). And also present was ethanol (blood, 0.165 and 0.145 g/100 mL) as well as the qualitative presence of cannabinoids (in both).

Barrett, P.J. Ecstasy and Dandrolene. British Med. J. 305 1225 (1992).

An argument is made against the administration of Dandrolene in instances of hyperthermia following ecstasy intoxication. This is a muscle relaxant which may reduce thermogenesis associated with muscular activity. Rehydration seems the wiser course and supportive measures may be sufficient treatment.

Benazzi, F., and Mazzoli, M. Psychiatric Illness Associated with "Ecstasy". Lancet 338 1520 (1991).

A case of severe depression following MDMA exposure is reported. The syndrome included loss of energy, weight, and interest in all activities, decreased appetite, psychomotor retardation, hypersomnia, diminished ability to concentrate, and suicidal ideation.

Brown, C.R., McKinney, H., Osterloh, J.D., Shulgin, A.T., Jacob III P. and Olson, K.R. Severe Adverse Reaction to 3,4-Methylenedioxymethamphetamine (MDMA). Vet. Hum. Toxicol. 28 490 (1986).

A 32 year old female presumably ingested a "standard" dose, and became comatose, but survived. Serum level was reported to be 7 micrograms/mL.

Brown, C. and Osterloh, J. Multiple Severe Complications from Recreational Ingestion of MDMA (Ecstasy). J. Am. Med. Soc. 258 780-781 (1987).

A considerable body of clinical detail and selected laboratory finding is present in an apparent MDMA toxicity situation involving a 32 year old female. Serum levels of 7 mg/mL and urine levels of 410 and 816 mg/mL were reported (the latter upon admission and on the second day). An immunoenzyme assay for MDMA (using a system designed for amphetamine) reacted with MDMA at 25 mg/mL at the amphetamine cut-off point of 300 nanograms/mL. The observed complications were similar to those observed in amphetamine overdoses, and might possibly be due to an idiosyncratic reaction, an allergic reaction, or to malignant hyperthermia.

Campkin, N.T.A. and Davies, U.M. Another Death from Ecstasy. J. Royal Soc. of Med. 85 61 (1992).

A young male was admitted both unconscious and convulsing following the consumption of three ecstasy tablets. Despite heroic treatment, he died some five hours later. Serum MDMA levels were measured (1.26 mg/L) although no MDA was detected. The diagnosis included disseminated intravascular coagulation with prolonged clotting times, hypofibrinogenaemia, elevated fibrin degradation products and thrombocytopaenia.

Chadwick, I.S., Linsley, A., Freemont, A.J. and Doran, B. Ecstasy, 3,4-Methylenedioxymethamphetamine (MDMA), a Fatality Associated With Agulopathy and Hyperthermia. J. Royal Soc. Med. 84 371 (1991).

A fatality associated with MDMA is reported. Blood and gut levels are given. Extensive morbid post mortem details are also outlined.

Davis, W.M., Hatoum, H.T. and Waters, I.W. Toxicity of MDA (3,4-Methylenedioxyamphetamine) Considered for Relevancy to Hazards of MDMA (Ecstasy) Abuse. Alcohol and Drug Abuse, 7 123-134 (1987).

The toxicological literature is reviewed, and it is suggested that the toxicological data obtained from MDA be extrapolated to MDMA. A comparison of these two drug is presented.

de Silva, R.N. and Harries, D.P. Misuse of Ecstasy. British Med. J. 305 309 (1992).

This is the reinstatement of four observed cases of intracerebral haemorrhage following exposure to ecstasy or amphetamine. The original article appeared in the Scottish Med. Journal, authored by Harries and de Silva..

Dowling, G.P. Human Deaths and Toxic Reactions Attributed to MDMA and MDEA. The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA. Kluwer, New York. (1990) Ed: S.J. Peroutka.

A thorough review is presented of the case records of the reported deaths associated with MDMA use. It was concluded that such deaths are exceedingly rare, especially when considering the widespread use of this drug.

Dowling, G.P., McDonough III, E.T. and Bost, R.O. 'Eve' and 'Ecstasy' A Report of Five Deaths Associated with the Use of MDEA and MDMA. J. Am. Med. Assoc. 257 1615-1617 (1987)

Five deaths occurred in the Dallas area which have involved either MDMA or MDE. One death was stated to be due to MDMA. Two of the others had had preexisting heart conditions, one had asthma, and one was electrocuted, apparently from having climbed and fallen from a power pole. In these latter cases, MDMA was not felt to have been the primary cause of death. It is suggested that a preexisting cardiac disease may predispose an individual to sudden death with MDMA. It was only with the asthma death that there was given a body level (blood) of MDMA, and it was 1.1 mg/mL.

Ellis, P. and Schimmel, P. Ecstasy Abuse. New Zealand Medical Journal 102 358 (1989).

A severely disturbed young woman was seen as a patient. She made frequent references to "Ecstasy." A urine analysis showed no evidence for the presence of MDMA, although there was observed a high level of phenothiazines. She was admitted to the psychiatric word and started on antipsychotic medication. After three days there, she committed suicide. The authors conclude, "We are concerned that clinicians should be aware of the potentially serious medical and psychiatric consequences of the use of [MDMA] in sensitive individuals or in overdose."

Ellis, S.J. Complications of "Ecstasy" Misuse. Lancet 340 726 (1992).

A criticism is levelled at the medical letters published, and especially the media coverage, concerning the association of ecstasy use and human trauma. The terms used, are judgmental and scaremongering. The danger associated with MDMA use is clouded by the reports being out of context. In the absence of correlary information such as alcohol consumption, or even an estimate of MDMA use.

Fahal, I.H., Sallomi, D.F., Yaqoob, M. and Bell, G.M. Acute Renal Failure after Ecstasy. British Med. J. 305 29 (1992).

A nearly lethal case of acute renal failure is reported six hours following the alleged ingestion of three "ecstasy" tablets at a rave. It is felt that the use of the drug may have contributed to the trauma.

Gorard, D.A., Davies, S.E. and Clark, M.L. Misuse of Ecstasy. British Med. J. 305 309 (1992).

A case of jaundice is reported in a young student who had been using ecstasy recreationally over a period of several months. The symptoms cleared and there were no complications.

Harries, D.P. and de Silva, R.N. 'Ecstasy' and Intracerebral Haemorrhage. Scottish Med J. 37; 150-152 (1992).

Four cases of intracerebral haemorrhage are reported, following exposure to amphetamine ecstasy, or mixtures thereof.

Hayner, G.N. and McKinney, H. MDMA The Dark Side of Ecstasy. J. Psychoactive Drugs 18 341-347 (1986).

The emergency treatment of two toxic episodes involving MDMA are described. One case, a 34 year old male, had a complex drug history involving mainly opiates, but the timing of the crisis suggested that MDMA injection was responsible. The other case, involving a 33 year old female, has been discussed in detail (see Brown et al., above). A listing of the side-effects that may be experienced in cases of MDMA toxicity is also presented.

Henry, J. A. Ecstasy and the Dance of Death. British. Med. J. 305 5-6 (1992).

The positives and negatives of the drug Ecstasy (MDMA) are weighed. On the positive side, the psychotherapeutic potentials in fields as divergent and marriage guidance, alcoholism, and enhancement of perception in elderly people, have been explored, although they have been found to be without benefit. On the negative side, the adverse effects can include convulsions, collapse, hyperpyrexia, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure, weight loss, exhaustion jaundice, "flashbacks,", irritability, paranoia, depression, or psychosis. The long term effects will take time to document in detail.

Henry, J.A., Jeffreys, K.J. and Dawling, S. Toxicity and Deaths from 3,4-Methylenedioxymethamphetamine ("Ecstasy"). Lancet 340 384-387 (1992).

A report of the seven or so deaths within the United Kingdom, associated with the use of MDMA, is presented. The clinical data in these deaths, as well as in other, non-fatal, legal situations, are brought together, and discussed. Most of the lethal events involved hyperthermia, whether from the effects of the drug itself, or from circumstances associated with its use.

Hughes, J.C., McCabe, M. and Evans, R.J. Intracranial Haemorrhage Associated with Ingestion of 'Ecstasy.' Arch. Emerg. Med. 10 372-374 (1993).

The summary of this report emphasizes the importance of a drug analysis in emergency medicine. The drug in this case was found to be amphetamine, not MDMA. Some mention should have been made also about the importance of not constructing a totally misleading title. Ecstasy was not involved.

Keenan, E., Gervin, M., Dorman, A. and O'Connor, J.J. Psychosis and Recreational Use of MDMA ("Ecstasy"). Irish J. Psychological Med. 10 162-163 (1993).

A patient presented with bizarre behavior, paranoid delusions and intermittant auditory hallucinations. He gave a history of taking MDMA weekly for a period of some five months. During his recovery period (with chlorpromazine) over the following few months, he has stopped the use of MDMA, and finds that the occasional use of cannabis does not worsen his symptoms.

Krystal, J.H., Price, L.H., Opsahl, C., Ricaurte, G.A. and Heninger, G.R. Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use: Effects on Mood and Neuropsychological Function? Am. J. Drug Alcohol Abuse 18 331-341 (1992).

A group of self-acknowledged past MDMA users, participants in a tryptophan challenge test, were evaluated for a number of possible neuropsychological deficits in a battery of tests. There were no indications of deficit, although some mild memory impairment was suggested. This was felt to be inconsequential (the volunteers that just recently flown some distances to participate in the tests, and the only documented drug common to all subjects was the intentionally administered tryptophan. The conclusions, nonetheless, are framed to raise concerns about the possible detrimental effects of MDMA use.

Larner, A.J. Complications of "Ecstasy" Misuse. Lancet 340 726 (1992).

An extensive discussion is presented on the mechanism of thermogenesis caused by the use of MDMA. There may indeed be a genetic predisposition to such forms of hyperthermia. Intervention with Dandrolene, although it itself is not centrally active, may be justified.

Lee, J.W.Y. Catatonic Stupor After Ecstasy. Brit. Med. J. 308 717-18 (1994).

The author has re-evaluated the diagnosis of two patients reported to have suffered catatonia as a consequence of having taken MDMA (Maxwell et al., Brit. Med. J. 307 1399 (1993). He feels from the symptoms presented, that one was stuporous and suffered mutism, and the other, who also did not speak, had simply presented with a "wild-eyed" look. The text-book criteria for a catonia diagnosis are reviewed.

McCann, U.D. and Ricaurte, G.A. Lasting Neuropsychiatric Sequelae of (+/-) Methylenedioxymethamphetamine ("Ecstasy") in Recreational Users. J. Clin. Psychopharm. 11 302-305 (1991).

The prolonged responses of two patients, who had allegedly ingested large quantities of MDMA, are described. It is suggested that there may be lasting adverse functional consequences in vulnerable persons following large dose exposure.

McGuire, P. and Fahy, T. Chronic Paranoid Psychosis after Misuse of MDMA ("Ecstasy"). British Med. J. 302 697 (1991).

Two cases are reported of chronic paranoid psychosis that followed alleged long-term self-administration of large quantities of MDMA. Other drugs had also been involved, and no toxicological evidence could confirm the drug history. Intervention treatment (Haloperidol, Sulpiride) resulted in some improvement.

O'Neill, D. and Dart, J.K. Methylenedioxyamphetamine (Ecstasy) Associated Keratopathy. Eye 7 805-806 (1993).

Three instances of othrwise unexplained corneal epitheliopath are described following the alledged taking of "Ecstasy." Although no documetation of drug exposure is mentioned, the drug has been assumed to be methylenedioxymethamphetamine (MDMA), rather than the methylenedioxyamphetamine (MDA) mentioned in the title and the text.

Pallanti, S., and Mazzi, D. MDMA (Ecstasy) Precipitation of Panic Disorder. Biol. Psychiatry 32 91-95 (1992).

The authors describe three patients whose panic disorder began during recreational use of MDMA (Ecstasy) and was subsequently complicated by agoraphobic avoidance that continued autonomously after cessation of the drug. Their panic disorder responded well to serotoninergic antidepressant drugs, although there was no psychotherapy done to work through the cause of the panic.

Peroutka, S.J., Pascoe, N. and Faull, K.F. Monoamine Metabolites in the Cerebrospinal Fluid of Recreational Users of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"). Res. Commun. Subst. Abuse 8 125-138 (1987).

Lumbar punctures from five MDMA users with various histories were assayed (some weeks following the last exposure) for the levels of metabolites from the three major neurotransmitters serotonin, dopamine, and norepinephrine. All assays fell within normal limits.

Price, L.H., Ricaurte, G.A., Krystal, J.H. and Heninger, G.R. Neuroendocrine and Mood Responses to Intravenous L-Tryptophan in 3,4-Methylenedioxymethamphetamine (MDMA) Users. Arch. Gen. Psychiat. 46, 20-22 (1989).

Nine self-acknowledged MDMA users were used as test subjects for the determination of the ability of tryptophan to increase the serum prolactin level. This response can be used as a measure of serotonin integrity There was a statistically insignificant lessening of PRL concentrations in the MDMA users.

Reynolds, P.C., Personal Communication, 1986.

A 35-years old male, who claimed to have taken MDMA, Valium, and LSD (and who died shortly after admission) had the following body levels (in mg/mL):

Blood Urine Bile Gastric (total) MDMA 1.46 13.7 1.98 414 mg. MDA .03 (present)

Neither diazepam nor nordiazepam were found.

Ricaurte, G.A. Studies of MDMA-Induced Neurotoxicity in Nonhuman Primates: A Basis for Evaluating Long-Term Effects in Humans. NIDA Research Monograph Series #94 306-322 (1989).

Dose-related serotonin depletion in experimental animals is tabulated. A comparison of primate results to those reported from rats, has allowed an extrapolation to the human MDMA-user. The conclusion drawn that, as there have been no clear indicators of problems with MDMA users, if there is damage in man it may be very subtle in nature, possibly lying outside of our present techniques for detecting it, and possibly being very slow in onset, as compared to the rapid consequences seen from the MPTP trauma in the dopaminergic system.

Rittoo, D.B. and Rittoo, D. Complications of "Ecstasy" Misuse. Lancet 340 725 (1992).

A cautionary note is sounded about the misinterpretation of the origins of hyperthermia as a complication in the course of anesthesia, when in fact it might be the result of prior MDMA ingestion. A serum level for MDMA is suggested as a protective manoeuvre.

Rittoo, D., Rittoo, D.B. and Rittoo, D. Misuse of Ecstasy. British Med. J. 305 309-310 (1992).

Three teenagers were observed with chest pains following the use of ecstasy and alcohol, and several hours of dancing. All electrocardiograms and radiographs were normal, and there were no complications.

Rohrig, T.P. and Prouty, R.W. Tissue Distribution of Methylenedioxymethamphetamine. J. Anal. Tox. 16 52-53 (1992).

Two cases of death involving methylenedioxymethamphetamine (MDMA) are reported; one case is a fatal acute overdose and the other is a drug-related death. The tissue distribution of MDMA is reported in both cases.

Russell, B., Schwartz, R.H. and Dawling, S. Accidental Ingestion of 'Ecstasy' (3,4-Methylenedioxymethylamphetamine). Archiv. Dis. Childhood 67 1114-1115 (1992).

A case is reported of a 13 month old boy who ingested one capsule of Ecstasy. Neurological and cardiovascular side effects predominated, which responded well to treatment with a Chlormethiazole infusion.

Sawyer, J. and Stephens, W.P. Misuse of Ecstasy. British Med. J. 305 310 (1992).

Two cases of "fits" are reported in young patients who had consumed Ecstasy. There were no complications or sequelae.

Schifano, F. Chronic Atypical Psychosis Associated with MDMA ("Ecstasy") Abuse. Lancet 338 1335 (1991).

A psychotic state is described in a patient who had been using MDMA on occasion over the course of four years. Other drugs (cannabis, alcohol, benzodiazepines, cocaine) were also used, sporadically. Neuroleptic therapy did not appear to improve his mental state.

Screaton, G.R., Cairns, H.S., Sarner, M., Singer, M., Thrasher, A. and Cohen, S.L. Hyperpyrexia and Rhabdomyolysis after MDMA ("Ecstasy") Abuse. Lancet 339 677-678 (1992).

Three cases are described that alledgedly involved the use of MDMA and came to medical attention because of extreme hyperthermia. Disseminated intravascular coagulation (DIC) apparently followed as a consequence of the hyperpyrexia. Rapid cooling of the patient is recommended in such cases.

Shearman, J.D., Chapman, R.W.G., Satsangi, J., Ryley, N.G. and Weatherhead, S. Misuse of Ecstasy. British Med. J. 305 309 (1992).

A woman experienced acute jaundice on two occasions, in from one to two weeks following the use of ecstasy, suggesting an idiosyncratic response to the drug.

Shulgin, A.T. and Jacob III, P. 1-(3,4-Methylenedioxyphenyl)-3-aminobutane: A Potential Toxicological Problem. J. Toxicol. - Clin. Tox. 19 109-110 (1982).

An alert is written for the toxicological community that through the ambiguity of the term "piperonylacetone," two different chemical precursors for both MDA and MDMA have been publicly advertised and made available. Efforts to synthesize MDMA might, through misrepresentation, yield a largely unexplored homologue.

Smilkstein, M.J., Smolinske, S.C., Kulig, K.W. and Rumack, B.H. MAO Inhibitor/MDMA Interaction: Agony after Ecstasy. Vet. Hum. Toxicol. 28 490 (1986).

An abstract of a report of a 50 year old male who injected alleged MDMA while on a fixed regimen of the monoamine oxidase inhibitor phenelzine. He developed severe hypertension, diaphoresis, an altered mental status, and marked hypertonicity. With supportive care he recovered fully in some 6 hours. Caution is expressed in possible interrelations between MDMA and MAO inhibitors.

Smilkstein, M.J., Smolinske, S.C. and Rumack, B.H. A Case of MAO Inhibitor/MDMA Interaction: Agony after Ecstasy. Clin. Toxicol. 25 149-159 (1987).

This is the actual published paper that appeared as an abstract under similar authorship and similar title above. There are considerable clinical details concerning the emergency room intervention.

Stone, R.J. Response to the paper of Singarah and Laviec. Anaesthesia 48 83 (1993).

Tests are suggested that might assay the hyperthermia aspects of MDMA intoxication. Perhaps those who succumb to acute toxicity may be expressing responses that are genetic mediated.

Suarez, R.V. and Riemersma, R. "Esctasy" and Sudden Cardiac Death. Amer. J. Forensic Med. Pathol. 9 339-341 (1988).

An apparently natural death involving cardiac problems has been found to be related to MDMA use. The drug levels are given for blood and urine, but none of the metabolite MDA was identified as being present.

Tehan, B. Ecstasy and Dantrolene. Brit. Med. J. 306 146 (1993).

An argument is advanced supporting the clinical intervention with Dantrolene in MDMA toxicity cases. This is supported by the successful outcome of a problem associated with MDE where body temperature responded quickly to the use of this agent.

Verebey, K., Alrazi, J. and Jaffe, J.H. The Complications of "Ecstasy" (MDMA). J. Am. Med. Assoc. 259 1649-1650 (1988). Osterloh, J. and Brown, C., In Reply. ibid. 259 1650 (1988).

The body levels of MDMA and MDA following a single human trial of 50 mg are given. The peak plasma level seen (105.6 ng/Ml at 2 hrs.) decreased to 5.1 ng/Ml at 24 hrs. MDA occurred in plasma at lower levels, and both compounds appeared in urine. This suggests that the toxic incident reported by Brown and Osterloh may have followed a considerable overdose.

Whitaker-Azmitia, P.M. and Aronson, T.A. "Ecstasy" (MDMA)-Induced Panic. Am. J. Psychiat. 146 119 (1989).

Three cases are reported of transient panic attacks in individuals following the ingestion of alleged MDMA.

Williams, H., Meagher, D. and Galligan, P. M.D.M.A. ("Ecstasy"); a Case of Possible Drug-induced Psychosis. Irish J. Med. Sci. 162 43-44 (1993).

A disturbed and aggressive patient was seen at the time of a police arrest, some 48 hours following the consumption of a half-tab of alledged MDMA His medical history included a skull fracture two months earlier, and his mother had a history of psychotic depression and paranoid delusions. His urine analysis showed only cannabis and benzodiazepines, the latter medically administered. His bizarre behavior and mental disorientation was treated with Haloperidol, Diazepam, Carbamazepine, and finally with a total of 600 mg Clopenthixol which allowed an eventual resolution of his psychosis and disorientation.

Winstock, A.R. Chronic Paranoid Psychosis after Misuse of MDMA. British Med. J. 302 1150-1151 (1991).

A brief survey of the frequency and nature of use of MDMA is presented. A check list of reported symptoms is given, and the suggestion is offered that as it might induce psychosis more research is needed.

Wodarz, N. and B=F6ning, J. "Ecstasy" - Induziertes Psychotisches Depersonalisationssyndrom. Nervenarzt 64 478-80 (1993).

Following the consumption of two tablets of MDMA, a 21-year old patient exhibited a psychotic depersonalisation disorder with suicidal tendencies. With medication, the symtoms disappered over the course of six months. "Flash-backs" occurred repeatedly.

Woods, J.D. and Henry, J.A. Hyperpyrexia Induced by 3,4-Methylenedioxyamphetamine ("Eve") Lancet 340 305 (1992).

A 30 year old man was admitted in convulsions, two hours after having taken six tablets of ecstasy. He recovered and was dismissed 72 hours later. Serum analysis showed the presence of 1.51 mg/L MDA and 0.2 g/L ethanol. The urine level of MDA was 48.6 mg/l but an analysis for MDMA showed only 0.5 mg/l as being present. Errors in synthesis were suspected. The original ingestion of MDMA is unlikely as MDA is only a minor metabolite of it.