No evidence of Ecstasy neurotoxicity exists
[title by editor of BMJ, not author!]
On 17th August 1996, the British Medical Journal published a response to the their editorial of 15th June entitled Ecstasy and neurodegeneration, refuting each of the points made by reference to published research.
In that article, Prof. Green warned that Ecstasy is likely to result in serious long-term consequences, possibly comparable to Parkinson's disease.
Evidence against Ecstasy being neurotoxic is provided by recent approval of a slimming pill called fenfluramine (widely used in Europe for many years without harmful effects). Tests which indicate Ecstasy as neurotoxic also indicate that fenfluramine is neurotoxic. Yet fenfluramine has recently been approved in the USA for unlimited use on the grounds that its benefits outweigh possible risks. This was because the US Food and Drug Administration expert committee did not accept the test results were valid. When applied to Ecstasy, however, identical test results have been used as proof of neurotoxicity.
Quite independently, recently published research established that there was no neurotoxicity in humans in cases where it was predicted by animal studies.
The association with Parkinson's disease is shown to be unfounded, and it is pointed out that although Ecstasy has been widely used for over two decades in the USA, the predicted casualties have not materialised.
The actual response follows: In their editorial on ecstasy (3,4-methylenedioxymethamphetamine) and neurodegeneration A Richard Green and Guy M Goodwin state that young people who misuse ecstasy should be fully informed of the risks, which they claim are considerable in the long term.1 The authors cite animal studies indicating that recreational use of ecstasy can cause neurotoxicity to the serotoninergic systems of the brain. The fact that the United States Food and Drug Administration recently (in May) approved dexfenfluramine for daily long term use could, however, imply that ecstasy is similarly safe for long term use. This is because much evidence of neurotoxicity, based on markers in animal studies, applies to research on both drugs. In this context G A Ricaurte (whose evidence is cited in the editorial) believes that neurotoxicity produced by dexfenfluramine is identical with that produced by ecstasy (personal communication, October 1995). Indeed, Green himself, with colleagues, has implicitly equated the neurotoxic effects of ecstasy with those produced by fenfluramine.2
Recent research casts further doubt on the methods used to provide evidence of neurotoxicity in humans. Postmortem examination of long term users of methamphetamine showed reduced levels of dopamine nerve terminal markers similar to those seen after use of ecstasy and fenfluramine. But the study went on to conclude that "levels of DOPA decarboxylase and the vesicular monoamine transporter, known to be reduced in Parkinson's disease, were normal. This suggests that chronic exposure to methamphetamine does not cause permanent degeneration of striatal dopamine nerve terminals at the doses used by the young subjects in our study" 3
The editorial suggests that use of ecstasy may eventually produce effects similar to Parkinson's disease, as was the case with MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridone). This is unlikely because the effects of MPTP were seen immediately. The analogy with MPTP -used by those who lobby for the prohibition of ecstasy in the United States - was long ago shown to be unfounded.4
The strongest evidence against such damage being a normal consequence of ingestion of ecstasy must surely be the small number of casualties among the large number of users over the past two decades. Psychiatric consequences are generally restricted to people with considerable premorbid psychopathology, polysubstance misuse, and histories of taking excessive amounts of ecstasy.5
There is no evidence to show that ecstasy is neurotoxic in humans. Since the possibility of neurotoxicity is a matter of great public concern, however, it should be urgently investigated by research on human volunteers.
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1 Green A R, Goodwin G M. Ecstasy and neurodegeneration. BMJ 1996;312:1493-4. (15 June.)
2 Colado M I, Murray T K, Green A R. 5-HT loss in rat brain following 3, 4-methylenedioxymethamphetamine (MDMA), p-choroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine. Br J Pharmacol 1993;105:583-9.
3 Wilson J M, Kalasinsky K S, Levery A I, Bergeron C, Reibel G, Anthony R M,W et al. Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nature Medicine 1996;2:699-703.
4 Beck J, Morgan P. Designer drug confusion: a focus on MDMA. J Drug Educ 1986;16: 267-82.
5 McGuire P K, Cope H, Fahy T A. Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine ("Ecstasy"). Br J Psychiatry 1994;165:391-5.
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