Erowid.org: Erowid Reference 8988 : Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT : Aitchison KJ, Tsapakis EM, Huezo-Diaz P, Kerwin RW, Forsling ML, Wolff K

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Aitchison KJ, Tsapakis EM, Huezo-Diaz P, Kerwin RW, Forsling ML, Wolff K. “Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT”. J Psychopharmacol. 2012 Mar 01;26(3):408-18. <a name="ref">Aitchison KJ, Tsapakis EM, Huezo-Diaz P, Kerwin RW, Forsling ML, Wolff K.</a> <a href="/references/8988">"Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT"</a> <i>J Psychopharmacol</i>. 2012 Mar 01;26(3):408-18.
Text Abstract (this page) Full Text - English (private) Show Articles by Aitchison KJ Tsapakis EM Huezo-Diaz P Kerwin RW Forsling ML Wolff K Article IDs Erowid RefID: 8988 PubMedID: 22303032 Collections Hofmann Collection MDMA Collection All References	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.
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Status: display earth Mar 22, 2016 1:02	No Clinical Value # The editors for Psychopharmacology should be ashamed. This title is misleading to the point of being a lie. None (0) of those studied qualified as hyponatraemic (hyponatremic) according to the authors' own definition. The differences between those who took MDMA and those who did not was of no clinical value. If they are statistically significant, they are equally useless for anyone following the issue. The authors fundraising line from their abstract is: "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." Deeper in their paper, they write : "Plasma osmolality for each subgroup remained above the cut-off for clinical diagnosis of hyponatraemia and SIADH." It is very important whether we have a detectable mechanism that explains why people react so differently to MDMA and related euphoric stimulants, but this paper is a lie wrapped around an exaggeration. The authors should be ashamed, but the editors of Psychopharmacology exemplify what is wrong with juried editing and publication. Very simply: no hyponatremia, no clinical significance, too few subjects, too many post-analysis subgroups, not enough power. * Do some liver enzyme genetic sub-type affect MDMA metabolism? yes, we've known that for twenty years. * Is it a major biological marker for problematic reactions to MDMA? We still have no idea. Know your Body, Know your Mind, Know your Substance, Know your Source. Be careful.
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