cn8b00590_si_001.xlsx (29.09 kB)
Role of Serotonin Transporter and Receptor Gene Variations in the Acute Effects of MDMA in Healthy Subjects
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posted on 2018-12-27, 00:00 authored by Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. LiechtiMethylenedioxymethamphetamine
(MDMA; ecstasy) is used recreationally
and has been investigated as an adjunct to psychotherapy. Most acute
effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine
[5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms
(SNPs) and polymorphic regions in 5-HT system genes, may contribute
to interindividual differences in the acute effects of MDMA. We characterized
the effects of common genetic variants within selected genes that
encode the 5-HT system (TPH1 [tryptophan 5-hydroxylase
1] rs1800532 and rs1799913, TPH2 [tryptophan 5-hydroxylase
2] rs7305115, HTR1A [5-HT1A receptor]
rs6295, HTR1B [5-HT1B receptor] rs6296, HTR2A [5-HT2A receptor] rs6313, and SLC6A4 [serotonin transporter] 5-HTTLPR and rs25531) on the physiological
and subjective response to 125 mg of MDMA compared with placebo in
124 healthy subjects. Data were pooled from eight randomized, double-blind,
placebo-controlled studies that were conducted in the same laboratory. TPH2 rs7305115, HTR2A rs6313, and SLC6A4 5-HTTLPR polymorphisms tended to moderately alter
some effects of MDMA. However, after correcting for multiple comparisons,
none of the tested genetic polymorphisms significantly influenced
the response to MDMA. Variations in genes that encode key targets
in the 5-HT system did not significantly influence the effects of
MDMA in healthy subjects. Interindividual differences in the 5-HT
system may thus play a marginal role when MDMA is used recreationally
or therapeutically.
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MDMAinterindividual differences2ASLC 6A5- HT system genesSNPTPH 1125 mg5- HTTLPRInterindividual differencespolymorphic regionsserotonin transporter5- HT systemHTRHealthy Subjects MethylenedioxymethamphetamineGenetic variants1A1BAcute EffectsSLC 6A 5- HTTLPR polymorphismsplacebo-controlled studiessingle-nucleotide polymorphismsSerotonin TransporterReceptor Gene Variations
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