by Nicholas Saunders
[ Appendix 4 sec. 8 ] [ Index ] [ Appendix 4 sec 10 ]
Appendix 4: Bibliography Human toxicology
- 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
- 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
- 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
- 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
- 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
- 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
- Hughes, J.C., McCabe, M. and Evans, R.J. Intracranial Haemorrhage
Associated with Ingestion of 'Ecstasy.' Arch. Emerg. Med. 10 372-374
- 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
- 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
- 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
- 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,
- 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
- 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
- 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
- Russell, B., Schwartz, R.H. and Dawling, S. Accidental Ingestion of
'Ecstasy' (3,4-Methylenedioxymethylamphetamine). Archiv. Dis. Childhood 67
- 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
- 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
- Shulgin, A.T. and Jacob III, P. 1-(3,4-Methylenedioxyphenyl)-3-aminobutane:
A Potential Toxicological Problem. J. Toxicol. - Clin. Tox. 19 109-110
- 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
- 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
- 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
- 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
- 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.