Skip to content

CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4-methylene-dioxymethamphetamine in a controlled study in healthy individuals

Yasmin Schmid, Patrick Vizeli, Cédric M. Hysek, Katharina Prestin, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti

Pharmacogenetics and Genomics June 2, 2016 DOI: 10.1097/fpc.0000000000000231 (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Pooled analysis of eight double-blind, placebo-controlled crossover studies Peer reviewed
Sample size 139
Population Healthy individuals
Intervention MDMA
Topics MDMA
Keywords Cyp2d6 Pharmacology Pharmacokinetics Active metabolite Pharmacogenetics Pharmacodynamics Cmax Crossover study Placebo Cytochrome p450 Genotype Metabolism
Citations 52
Key points Polymorphic CYP2D6 activity alters MDMA disposition and effects, but the impact is small due to autoinhibition of CYP2D6.

Abstract

The role of genetic polymorphisms in cytochrome (CYP) 2D6 involved in the metabolism of 3,4-methylene-dioxymethamphetamine (MDMA, ecstasy) is unclear. Effects of genetic variants in CYP2D6 on the pharmacokinetics and pharmacodynamic effects of MDMA were characterized in 139 healthy individuals (70 men, 69 women) in a pooled analysis of eight double-blind, placebo-controlled crossover studies. In CYP2D6 poor metabolizers, the maximum concentrations (Cmax) of MDMA and its active metabolite 3,4-methylene-dioxyamphetamine were +15 and +50% higher, respectively, compared with extensive metabolizers and the Cmax of the inactive metabolite 4-hydroxy-3-methoxymethamphetamine was 50-70% lower. Blood pressure and subjective drug effects increased more rapidly after MDMA administration in poor metabolizers than in extensive metabolizers. In conclusion, the disposition of MDMA and its effects in humans are altered by polymorphic CYP2D6 activity, but the effects are small because of the autoinhibition of CYP2D6.

Comparable studies

Other randomized controlled trials on MDMA, most cited first.

Study Year Design Participants
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Patients with severe PTSD, including those with comorbidities such as dissociation,... 2021 Randomized controlled trial n = 90
The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Patients with chronic post-traumatic stress disorder refractory to both psychotherapy... 2010 Randomized controlled trial n = 20
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Military veterans and first responders aged 18 or older with chronic PTSD lasting 6... 2018 Randomized, double-blind, dose-response, phase 2 clinical trial n = 26
A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) Patients with treatment-resistant PTSD 2012 Randomized controlled trial n = 12
MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Adults with moderate to severe post-traumatic stress disorder 2023 Randomized controlled trial n = 104

Citations in the library

Cited by 36

and 31 more in the library

Cites 7

and 2 more in the library

Related reading

Explore topics

MDMA