E for Ecstasy by Nicholas Saunders
Appendix 1: Reference Section

68 A Trip into the Unknown, by Alison Abbott and David Concar, in New Scientist, 29/8/92

The authors estimate half a million E's will be taken "this weekend alone". "It is hard to build up a convincing case against the drug when you can't say exactly how dangerous it is or what the consequences of long-term effects are," they say. They make the following points: Britain has no long term research programme; the consensus is that ecstasy's hallucinogenic properties render it wholly unsuitable as a medical drug; figures released in August 1992 from the National Poisons Unit at Guy's Hospital showed that the drug had killed 7 people since 1990; pathologists are sure of the cause: heatstroke; Dr. John Henry of the NPU told them that everyone who takes Ecstasy is a potential victim, but is most worried by contamination of MDMA with heroin and ketamine.

MDMA works by blocking the return of 5HT [serotonin] to neurons by occupying its binding sites on the transporter protein. Once inside the neuron MDMA cannot be stored so leaks out again. As a result, the levels of 5HT in the synapses rise sharply in the short term, and 5HT signalling between neurons is amplified. The 'high' eventually fades when neurons become drained of their stored 5HT. Antidepressants like fluoxetine are thought to work by boosting levels of 5HT in the same way as Ecstasy. Most of the amphetamine-like effects are probably caused by increased levels of noradrenaline. The observed rise in body temperature in rats in hot environments may be caused by increased levels of 5HT in the part of the brain that regulates temperature known as the hypothalamus. This may render the hypothalamus unable to respond appropriately to overheating caused by dancing.

Research on rats shows the drug causes the nerve fibres or axons, through which 5HT neurons communicate with the rest of the brain, to break and swell. "On top of that, Ecstasy appears to block the activity of an enzyme called tryptophan hydroxylase, which neurons need to synthesise 5HT," the authors say.

"It could be years before the health risks of chronic abuse of ecstasy show up in the statistics," they conclude.