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

Alan O'Donohoe, Karen O’flynn, Kevin Shields, Ziarih Hawi, Michael Gill

Addiction Biology July 1, 1998 DOI: 10.1080/13556219872119 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Retrospective case series Case report Peer reviewed
Sample size 7
Population Individuals who had an adverse reaction or death thought due to MDMA
Topics MDMA
Keywords Cyp2d6 Genotype Toxicity Pharmacology Population Genotyping Debrisoquine Drug Genetics
Citations 29
Key findings None of the seven cases of MDMA toxicity or death were homozygous for the CYP2D6 mutation.

Abstract

Abstract 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.

Comparable studies

Other case reports and case series on MDMA, most cited first.

Study Year Design Participants
'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA Individuals whose deaths were associated with MDMA or MDEA use 1987 Case series n = 5
Pathology of deaths associated with "ecstasy" and "eve" misuse. Young white men aged 20 to 25 who died after using ring-substituted amphetamines (MDMA... 1996 Case series n = 7
'Eve' and 'Ecstasy' Individuals who died after using MDMA or MDEA 1987 Case series n = 5
A Method of Conducting Therapeutic Sessions with MDMA Clients with clear therapeutic purpose, excluding those with serious functional... 1998 Case study n = 2
Diversity of Psychopathology Associated with use of 3,4-Methylenedioxymethamphetamine (‘Ecstasy’) Psychiatric patients presenting between 1990 and 1992 whose symptoms developed in the... 1994 Case series n = 13

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