Pharmacogenetics and Genomics
June 2, 2016
Yasmin Schmid, Patrick Vizeli, Cédric M. Hysek et al.
52 citations
Genetic variants in the CYP2D6 enzyme, which metabolizes MDMA (ecstasy), alter the drug's pharmacokinetics and effects. In a pooled analysis of eight double-blind, placebo-controlled crossover studies involving 139 healthy individuals (70 men, 69 women), people with poor CYP2D6 metabolism had 15% higher peak concentrations of MDMA and 50% higher peak concentrations of its active metabolite, while the inactive metabolite was 50-70% lower, compared to extensive metabolizers. Blood pressure and subjective drug effects also increased more rapidly in poor metabolizers. However, these differences are small because MDMA itself inhibits CYP2D6 activity.
Clinical Pharmacology & Therapeutics
February 28, 2025
Lorenz Mueller, Alen Jelusic, Avram Tolev et al.
15 citations
In a double-blind, placebo-controlled crossover study with 23 healthy participants, daily paroxetine (an SSRI antidepressant) did not reduce the pleasant subjective effects of a single 100 μg dose of LSD, but it significantly lessened negative effects such as 'bad drug effect,' anxiety, and nausea. Paroxetine increased LSD's peak concentration and total exposure by 40% and 50%, respectively, by inhibiting the CYP2D6 enzyme, indicating this enzyme is involved in LSD metabolism. The interaction was strongest in normal CYP2D6 metabolizers and weakest in poor metabolizers. The findings suggest LSD can be safely added to SSRI treatment without dose adjustment when the SSRI inhibits CYP2D6, but no definitive recommendation can be made for other SSRIs.
European Journal of Clinical Pharmacology
December 2, 2017
Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
15 citations
Genetic variants of the norepinephrine transporter gene (SLC6A2) weakly influence the acute cardiovascular response to MDMA (ecstasy). In a pooled analysis of eight double-blind, placebo-controlled studies involving 124 healthy subjects, carriers of the GG genotype of the rs1861647 SNP showed higher increases in heart rate and rate-pressure product after MDMA than those with one or no G alleles. Subjects with a C allele in the rs2242446 SNP had greater heart rate elevations compared with the TT genotype. The AA genotype of the rs36029 SNP was associated with higher increases in mean arterial pressure and rate-pressure product than carriers of the G allele. Two other SNPs (rs168924 and rs47958) did not alter MDMA responses. These genetic factors may play a minor role in adverse cardiovascular events during recreational MDMA use.
ACS Chemical Neuroscience
December 27, 2018
Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
13 citations
A pooled analysis of eight placebo-controlled studies in 124 healthy subjects tested whether common genetic variants in serotonin-system genes influence the physiological and subjective effects of 125 mg of MDMA. Variants in TPH2, HTR2A, and the serotonin-transporter gene showed only modest, non-significant associations after correction for multiple comparisons. No tested genetic polymorphism significantly altered the response to MDMA. The results suggest that interindividual differences in serotonin-system genes play a marginal role in MDMA's effects, whether used recreationally or therapeutically.