MDMA (midomafetamine) is being reviewed by the FDA to treat post-traumatic stress disorder. A phase I study found that a high-fat/high-calorie meal did not change MDMA plasma concentrations, only delayed the time to reach peak concentration. A population pharmacokinetic model showed no meaningful effects from age, weight, sex, race, or fed status. A physiologically based pharmacokinetic model predicted that splitting the clinical dose (120 or 180 mg MDMA HCl) into two doses two hours apart results in slightly lower early exposure and a delayed peak compared to a single dose. The model also confirmed MDMA is a strong inhibitor of CYP2D6 but does not meaningfully affect drugs cleared by renal transporters.
A modeling study designed an infusion protocol for the psychedelic compound DMT, aiming to maintain a specific level of psychedelic intensity. Using computer simulations based on pharmacokinetic/pharmacodynamic models, optimal doses to achieve intensity ratings between 7 and 9 on a 0-10 scale were a bolus of 14-16 mg DMT fumarate followed by an infusion rate of 1.2-1.4 mg/min. However, the proportion of simulated individuals achieving the target intensity was low (below 53%), indicating that individual dose adjustments would be necessary. Differences between the models were observed, particularly at scale boundaries, with bounded integer models predicting more cases exceeding the target than the continuous variable model.