Agony and ecstasy: a review of MDMA effects and toxicity.

BACKGROUND: Ecstasy is a recreational drug with an anecdotal reputation for safety. However, reports of adverse effects and fatalities have increased in the medical and popular press. METHOD: Literature search and review. RESULTS: Acute Ecstasy toxicity does not appear to be due to overdose and cannot be solely attributed to the nature of the usual ambient environment. Adverse effects include hyperthermia, seizures, cardiac arrhythmias, hepatotoxicity, hyponatraemia and many psychiatric disorders. Ecstasy causes serotonergic neurotoxicity in the brains of animals at doses close to those used by humans, but its long-term effect on the human brain is unknown. CONCLUSION: Ecstasy toxicity should be considered in the differential diagnosis of a variety of medical and psychiatric conditions. Given its popularity, both the acute and the potential long-term effects are a cause for concern.

MDMA toxicity: no evidence for a major influence of metabolic genotype at CYP2D6.

3,4 Methylenedioxymethamphetamine (MDMA or ecstasy) has become a major drug of abuse over the last decade. It produces a mixture of systemic and neuropsychological effects. Animal studies show a range of short- and long-term toxic effects, both systemically and neurochemically. In humans, toxicity and death due to the drug have been attributed to a variety of causes, with 'idiosyncratic', or non-dose-related, reactions often cited. It has recently been established that MDMA is metabolized via the cytochrome P450 enzyme, debrisoquine hydroxylase. This enzyme is coded by the gene CYP2D6. This gene contains mutations which effect the function of the enzyme, and individuals homozygous for these mutations are known as poor metabolizers. Between 3 and 10% of the Caucasian population are thus affected, and therefore may be less able to metabolize MDMA. In this paper we examine the hypothesis that individuals selected on the basis of having had an adverse reaction to MDMA will be more likely than the general population to have homozygous mutations at CYP2D6. We obtained retrospectively seven cases of toxicity or death thought to be due to MDMA. DNA was extracted from these patients, and their genotype ascertained. None of this small sample was shown to be homozygous for the mutation at CYP2D6. Three possible explanations are offered for these results. (1) The non-dose-related nature of MDMA toxicity may be due, either alone or in combination, to contaminants in the drug, or ambient environmental/physiological factors. (2) Our genotyping methods may have missed one of the rare additional mutations which effect gene function at CYP2D6. (3) Our study sample may be too small to demonstrate a statistically significant result. A larger study is currently under way.

The use of recombinant human erythropoietin in end stage renal disease.

We treated 57 patients who suffered from end stage renal disease (ESRD) with recombinant human erythropoietin (EPO) for a mean period of 56 weeks. Patients were aged between 18 and 81 years. Forty three patients were on haemodialysis and 14 on continuous ambulatory peritoneal dialysis (CAPD). Despite regular transfusions, the mean haemoglobin prior to EPO therapy was 7.4 g/dl +/- 1.7. The target haemoglobin of 10 g/dl was reached at a mean of 12 weeks for the CAPD patients and at 14 weeks for the haemodialysis population. Patients were noted during the study to have a progressive rise in mean red cell volume, and this appeared to be related to their level of iron stores. The mean dose EPO used to reach the target haemoglobin was 8,700 u/week (125 u/kg/week) for the haemodialysis patients and 7,200 u/week (102 u/kg/week) for the CAPD patients. Three patients (7%) developed thrombosis of their A/V fistula. Hypertension was exacerbated in 28% of the patients. We conclude that EPO is a very effective but not inexpensive therapy for the anaemia of ESRD.