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E for Ecstasy
by Nicholas Saunders

[ Appendix 4 sec. 7 ] [ Index ] [ Appendix 4 sec 9 ]

Appendix 4: Bibliography Animal toxicology

Allen, R.P., McCann, U.D. and Ricaurte, G.A. Persistant Effects of (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") on Human Sleep. Sleep, 16 560-564 (1993).

A number of MDMA users were studied as to sleep performance. They showed a significant decrease in sleep time (19 minutes) and non-REM sleep (23.2 minutes). The authors conclude that the recreational use of MDMA may induce lasting CNS serotonergic damage.

Ames, D. and Wirshing, W.C. Ecstasy, the Serotonin Syndrome, and Neuroleptic Malignant Syndrome - A Possible Link. J. Am. Med. Assoc. 269 869 (1993).

A short review of both the "serotonin syndrome" and the "neuroleptic malignant syndrome" are presented, and compared to the portrait presented with MDMA overdose. A path of medical intervention is suggested based on the neurotransmitter disturbances associated with these syndromes.

Barrett, P.J. 'Ecstasy' misuse - Overdose or Normal Dose? Anaesthesia 48 83 (1993).

The personal experiences of this physician is that there is no straightforward relationship the dose of 'ecstasy' used, and the complications that might follow this exposure. Dehydration is common, but this follows the energy expenditure in the drug use scene. Supportive therapy should be continued, but its efficacy must be continuously evaluated.

Campkin, N.T.A. and Davies, U.M. Treatment of 'Ecstasy' Overdose with Dandrolene. Anaesthesia, 48 82-83 (1993).

An exploration is presented for the first reported use of Dandrolene in the treatment of MDMA overdose. Its value in treatment is discussed, and remains uncertain. Nonetheless the recreational use of MDMA appears to remain a potentially lethal pastime.

Cregg, M.T. and Tracey, J.A. Ecstasy Abuse in Ireland, Irish Med. J. 86 118-20 (1993).

An epidemiological study of MDMA use in Ireland is presented, based upon reports to the National Poisons Information Centre in Dublin. Most of those described were male (80%) and largely in the 16-20 year old group. The symptoms presented are described as being relatively mild.

Davis, W.M. and Borne, R.F. Pharmacologic Investigation of Compounds Related to 3,4-Methylenedioxyamphetamine (MDA). Substance and Alcohol Actions/Misuse, 5 105-110 (1984).

Acute toxicity studies on MDMA and several homologues, in mice, showed LD-50's of about 100 mg/Kg (i.p.) (for MDMA). In aggregate, the lethality was increased several-fold.

de Man, R.A., Wilson, J.H. and Tjen, H.S. Acute Liver Failure Caused by Methylenedioxymethamphetamine ("Ecstasy"). Nederlands Tijdschrift voor Geneeskunde. 137 727-9 (1993).

An eighteen year old female who had regularly taken 1-2 tablets of MDMA every weekend, developed acute liver failure. She recovered following two months of hospitalization. It is claimed that this is the 10th published case of hepatotoxicity following MDMA use.

Friedman, R. Ecstasy, the Serotonin Syndrome, and Neuroleptic Malignant Syndrome - A Possible Link. Reply. J. Am. Med. Assoc. 269 869-870 (1993).

A plan for the treatment of MDMA toxicity is presented, based on the similarity of its symptoms with the "serotonin syndrome."

Frith, C.H. 28-Day Oral Toxicity of Methylenedioxymethamphetamine Hydrochloride (MDMA) in Rats. Project Report, Toxicology Pathology Associates, Little Rock, Arkansas (1986)

A controlled toxicological study on some 100 rats with chronically administered MDMA (dosages up to 100 mg/Kg) showed several behavioural signs (hyperactivity, excitability, piloerection. exophthalmus, and salivation). Neither gross nor microscopic pathology was evident at necropsy.

Frith, C.H., 28-Day Oral Toxicity of Methylenedioxymethamphetamine Hydrochloride (MDMA) in Dogs. Project Report, Toxicology Pathology Associates, Little Rock, Arkansas (1986)

A controlled toxicological study of some 24 dogs with chronically administered MDMA (dosages up to 15 mg/Kg) showed several behavioural signs including circling, depression, dilated pupils, hyperactivity, rapid breathing, and salivation. On necropsy, there were examples of reduced testicular size, including microscopically noted atrophy. Prostatic hyperplasia was present in two high dose males.

Frith, C.H., Chang, L.W., Lattin, D.L., Walls, R.C., Hamm, J. and Doblin, R. Toxicity of Methylenedioxy-methamphetamine (MDMA) in the Dog and the Rat. Fundamental and Applied Tox. 9 110-119 (1987).

Toxicity studies were performed on dogs and rats and signs are described. No histopathological lesions within the CNS were observed in either species, although unusual clinical observations were recorded.

Goad, P.T. Acute and Subacute Oral Toxicity Study of Methylenedioxymeth-amphetamine in Rats. Project Report, Intox Laboratories, Redfield, Arkansas, (1985).

Subacute toxicity studies on rats in graded doses (25 mg/Kg/day in 25 mg increments to 300 mg) were conducted. In acute studies, the LD-50 is given as 325 mg/Kg, some six times the reported i.p. LD-50. No histological evidence of brain damage was observed.

Gledhill, J.A., Moore, D.F., Bell, D. and Henry, J.A. Subarachnoid Haemorrage Associated with MDMA Abuse. J. Neurol. Neurosur. Psychiat. 56 1036-1037 (1993).

Shortly following the consumption of MDMA, a 25 year old woman presented with severe headache and vomiting. A CT scan showed subarachnoid haemorrhaging which was successfully controlled. There had apparently been a preexisting "berry" aneurysm which may have ruptured with the surge of blood pressure from the drug. She had been a regular MDMA user for two or three years before this incident.

Hardman, H.F., Haavik, C.O. and Seevers, M.H. Relationship of the Structure of Mescaline and Seven Analogs to Toxicity and Behaviour in Five Species of Laboratory Animals. Tox. and Appl. Pharmacology 25 299-309 (1973).

This report describes several studies supported by the Army Chemical Centre during the period 1953-1954, and declassified in 1969. MDMA was one of eight compounds (including also mescaline, DMPEA, MDPEA, MDA, DMA, TMA and alpha-ethyl-MDPEA) studied in five animals (mouse, rat, guinea pig, dog, and monkey).

The toxicology study showed MDMA to be one of the more toxic of the drugs studied, in most animals second only to MDA. The average LD-50's given were 97, 49 and 98 mg/Kg (for the mouse, rat and guinea pig, resp. - following i.p. administration), and 16 and 26 mg/Kg (for the dog and monkey, i.v. administration).

Behavioural studies in dog and monkey were made over the dosage ranges of 5-50 and 10-75 mg/Kg respectively. These levels evoked a broad range of motor activity, autonomic activity and CNS activity in both animals (the dog more than the monkey) but the ranges studied included the lethal dose levels. Interestingly the monkey showed behaviour interpreted as hallucinations for MDMA, whereas mescaline (an acknowledged hallucinogenic compound) produced no such behaviour at doses more than two times higher (200 mg/Kg i.v.). Structure-activity relationships are discussed.