E for Ecstasy by Nicholas Saunders
Appendix 1: Reference Section

74 Ecstasy: towards an understanding of the biochemical basis of the actions of MDMA, by Marcus Rattray, from Essays in Biochemistry, vol. 26 1991

Rattray reviews some of the complex biochemical actions of MDMA and discusses how these may relate to the psychopharmacological and neurotoxic effects of the drug.

After a single dose, 5HT depletion is rapid and remains low for 6-18 hours, recovering within 24 hours. This coincides with observed effects of MDMA. It is therefore likely that psychotropic effects can be ascribed to the post- and pre-synaptic effects of released 5HT.

Studies using brain slices pre-loaded with 5HT have shown that micro-molar concentrations of MDMA induce 5HT release. It has been proposed that the MDMA taken up by nerve terminals causes the displacement of 5HT from cytoplasmic binding sites, leading to 5HT efflux through the synaptoic membrane 5HT transporter. . . . this is taken as evidence that the neurotransmitter released is derived from cytoplasmic stores rather than from the 5HT stored in synaptic vesicles.

Drugs such as fluoxetine known to block 5HT uptake into nerve terminals are found to inhibit the release of 5HT induced by MDMA. Current evidence suggests that the primary action of MDMA is on the nerve terminals of neurons that synthesize and release the amine neurotransmitter serotonin or 5HT.

Answering the question: is MDMA toxic to man? Rattray says:

In all the studies that have found neuro-degeneration in animals, several large doses were administered over a very short time period, so it is difficult to extrapolate to humans. The route of drug administration (oral in humans) is a significant factor [ref. to Ricaurte 1989]. Nevertheless, it is likely that levels of consumption in man can produce brain concentrations that approach toxic doses. At the present time there are no reports of MDMA-induced neuro-degeneration in humans.