Long term neurotoxic effects of MDMA appear to require either a large single dose (20mg/kg or more) or several more moderate doses, typically 5 mg/kg twice daily for 4 consecutive days (Ricaurte et al 1988, O’shea et al 1998).  Neurotoxic effects are evident up to a year after drug administration in rats (Battaglia 1987) and have been observed 7 years after drug administration in non-human primates (Hatzdimitriou et al 1999).  The lowest MDMA dose which has been shown to elicit long term structural damage in non-human primates is 5mg/kg twice daily for 4 consecutive days (Ricaurte et al 1992). This is considerably higher than is typical in human recreational users but using the brain mass rather than the body mass ratio, which has been shown to be more accurate for interspecies scaling, (Tucker and Rostami 2000) leaves a much lower margin for complacency in human users.

Larger doses of MDMA in animals have been shown to reduce the levels of tryptophan hydroxylase, the rate limiting enzyme in 5-HT synthesis.(Ricaurte et al 1988). It is thought that this occurs because of oxidative stress which MDMA places on the neurone (O’shea et al 1998).  This oxidative stress might occur through several possible channels such as the metabolism of MDMA into a toxic quinoid, 5-HT derived toxins, 5-HT mediated cellular events, or temporary inhibition of monoamine oxidase and the exact mechanism is presently unknown. (Rattray 1991, O’shea 2001).  Oxidative stress may also lead to a variety of other complications though the evidence for this is at present limited.

Insufficient information is available to judge the levels of oxidative damage which are induced by MDMA use, but there is a strong body of evidence to suggest oxidative damage may be a cause of many types of neurodegenerative disease. Localisation of this damage may limit the extent to which MDMA use could contribute to Alzheimer’s disease, Parkinson’s disease or other such debilitating disorders. Should this prove to be a consequence, however, the economic cost to the health service of widespread MDMA use could potentially be huge, as neurodegenerative disorders require extensive, long term care.  Chronic depression is another possible consequence of MDMA use and again, the implications for society of a significant increase in people suffering from depression could be considerable
 

prev

next