In his study E-users certainly showed deficiencies in serotonin - the so called "happiness chemical" and this may be a factor in the problems E-users are currently experiencing. But, if even this is far from clear cut, the long-term effects are even more hotly disputed. As David Concar, deputy editor of New Scientist, explained in the Independent: "The really tricky point about this is whether you call these changes "damage", or whether they are "chemical responses" to the drug which would in time reverse themselves."Does MDMA lower serotonin to an extent that it will cause problems for the majority of users? Or, is it the case that E causes problems in specific types of people, who, due to their chemical make-up or mental state, are unusually susceptible? Moreover, does any change or damage last, or will the brain revert back to normal after use has ceased?The pessimists predict a bleak future that suggests those currently with problems are merely experiencing the calm before the storm. Although the connection is far from fully understood, low serotonin levels have been linked with depression in some studies. "But you could also say that it poses more questions than it answers."Results published in November last year by American scientist George Ricaurte, Assistant Professor of Neurology at John Hopkin's University, were similarly equivocal.

Dr Semple conducted brain scans and psychological tests on a group of volunteers who'd all used ecstasy for at least one year, and who had taken at least 50 tablets (although most had taken many more). "Does E, in the long term, cause effects on the brain? Yes, you could say that we've found something," says Dr Semple. (Though, significantly, most clubbers would have an anecdote or two.) Indeed, of 469 long term E-users questioned for Radio 5's The E Generation, broadcast in July last year, six out of ten said that they had been affected by depression and/or loss of memory.This month, Dr David Semple, of the Royal Edinburgh Hospital publishes new research into the effects of MDMA on the brain's serotonin and dopamine functions. These aren't simple cases of the mid-week blues.Amassing scientific data to try to establish a cause-and-effect link between E and mental health problems is problematic.

Clubbers take impure drugs, they take cocktails of drugs that may include amphetamines (amphetamine psychosis is already widely recognised) and they hide other factors, such as relationship troubles, that may predispose them to problems. Consequently, as John Ramsey, Head of Toxicology at Tooting's St George's Medical School and a consultant to the Health Education Authority, readily admits, current thinking is largely an amalgam of "medical intuition", animal research and anecdotal evidence from clubbers. All-consuming depression, anxiety - to the extent where the simplest social situations leave you rigid with fear - paranoia, hallucinations, psychosis and "panic attacks" have all been reported by drugs helplines, surveys and GPs. "And of those, a small number will go on to develop a significant problem." For that minority, however, the side-effects can be devastating.