MDMA-induced CYP2D6 inhibition: concentration-dependent variability using dextromethorphan as a probe
Drug Metabolism and Personalized Therapy June 16, 2026 Faezeh Ahmadi, Hoda Lavasani, Mohammadhosein Keshvadi et al.
A single dose of MDMA (ecstasy) inhibits the liver enzyme CYP2D6, but the duration of inhibition depends on the concentration of the probe drug used to measure enzyme activity. Using a therapeutic concentration of dextromethorphan (2 µM), enzyme activity was significantly reduced only at 1 hour after MDMA, with recovery by 1 week. Using a saturated concentration (300 µM), activity was reduced at 1 hour, 1 week, and 1 month. The results suggest that the apparent recovery time of CYP2D6 after MDMA exposure varies with probe concentration, likely due to differences in metabolic pathways at different substrate levels.