Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT.
J Psychopharmacol
; 26(3): 408-18, 2012 Mar.
Article
in En
| MEDLINE
| ID: mdl-22303032
ABSTRACT
We hypothesised that genetically determined poor metabolism of 3,4-methylene dioxymetamphetamine (MDMA) due either to the presence of CYP2D6 genotypes giving absent or low CYP2D6 enzyme activity, or a COMT genotype predicting low COMT enzyme activity would be associated with a greater degree of MDMA-induced reduction in plasma sodium and osmolality than other genotypes at these genes following consumption of 'ecstasy' tablets by clubbers. Of the 48 subjects who returned to the test site post-clubbing, 30 provided samples for measurement of vasopressin (AVP), plasma sodium, urea and plasma and urine osmolality. Genotyping was performed for functional variants in CYP2D6 (n = 29) and COMT (Val158Met, n = 30). In subjects with urinary MDMA detected post-clubbing, there was a significant association between change in plasma osmolality (p = 0.009) and in plasma sodium (p = 0.012) and CYP2D6 genotypic category. Individuals with the low-activity but readily inhibitable CYP2D6 extensive metaboliser/intermediate metaboliser (EM/IM) genotype showed greater reductions in these measures than all other CYP2D6 genotypic categories. COMT low-activity genotypes (Met/Met and Val/Met) were also significantly associated with reductions in plasma osmolality (p = 0.028) and in plasma sodium (p = 0.003). On conservative Bonferroni correction for two independent genes, the CYP2D6 and COMT plasma sodium findings remain significant. The relatively high frequency of the low-activity CYP2D6 and COMT genotypes in the population warrants further attention, since consumption of free water following ingestion of MDMA in these individuals may trigger dilutational hyponatraemia and increased risk of syndrome of inappropriate antidiuretic hormone secretion.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
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Illicit Drugs
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Catechol O-Methyltransferase
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N-Methyl-3,4-methylenedioxyamphetamine
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Cytochrome P-450 CYP2D6
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Hyponatremia
Type of study:
Etiology_studies
/
Incidence_studies
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Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limits:
Adolescent
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Adult
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Female
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Humans
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Male
Language:
En
Journal:
J Psychopharmacol
Journal subject:
PSICOFARMACOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
United kingdom