PMID- 22303032 OWN - NLM STAT- MEDLINE DCOM- 20120803 LR - 20191210 IS - 1461-7285 (Electronic) IS - 0269-8811 (Linking) VI - 26 IP - 3 DP - 2012 Mar TI - Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT. PG - 408-18 LID - 10.1177/0269881111434624 [doi] AB - 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. FAU - Aitchison, Katherine J AU - Aitchison KJ AD - MRC Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK. kaitchis@ualberta.ca FAU - Tsapakis, Evangelia M AU - Tsapakis EM FAU - Huezo-Diaz, Patricia AU - Huezo-Diaz P FAU - Kerwin, Robert W AU - Kerwin RW FAU - Forsling, Mary L AU - Forsling ML FAU - Wolff, Kim AU - Wolff K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120201 PL - United States TA - J Psychopharmacol JT - Journal of psychopharmacology (Oxford, England) JID - 8907828 RN - 0 (Illicit Drugs) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2D6) RN - EC 2.1.1.6 (Catechol O-Methyltransferase) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM CIN - J Psychopharmacol. 2013 Jan;27(1):115-6. PMID: 23255437 MH - Adolescent MH - Adult MH - Amino Acid Substitution MH - Biotransformation MH - Catechol O-Methyltransferase/*genetics/metabolism MH - Cohort Studies MH - Cytochrome P-450 CYP2D6/*genetics/metabolism MH - Female MH - Genetic Association Studies MH - Humans MH - Hyponatremia/*chemically induced/genetics/metabolism/urine MH - Illicit Drugs/pharmacokinetics/*toxicity/urine MH - Inappropriate ADH Syndrome/chemically induced/genetics/metabolism/urine MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/pharmacokinetics/*toxicity/urine MH - *Polymorphism, Genetic MH - Polymorphism, Single Nucleotide MH - Severity of Illness Index MH - Water-Electrolyte Balance/drug effects MH - Young Adult EDAT- 2012/02/04 06:00 MHDA- 2012/08/04 06:00 CRDT- 2012/02/04 06:00 PHST- 2012/02/04 06:00 [entrez] PHST- 2012/02/04 06:00 [pubmed] PHST- 2012/08/04 06:00 [medline] AID - 0269881111434624 [pii] AID - 10.1177/0269881111434624 [doi] PST - ppublish SO - J Psychopharmacol. 2012 Mar;26(3):408-18. doi: 10.1177/0269881111434624. Epub 2012 Feb 1.