3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) is used both recreationally and therapeutically. The pharmacodynamic effects of MDMA are diverse. Little is known about individual differences in the acute response to MDMA. Previous studies suggest that differences in the response to MDMA are in part due to genetic variations in the metabolism of MDMA. Additionally, effects of other psychoactive substances have been shown to be critically influenced by personality traits and mood states before drug intake.
Methods: The present analysis was based on 10 randomized, double-blind, placebo-controlled, cross-over studies with a total of 194 healthy subjects receiving either 75 or 125 mg of MDMA. The present study investigated the influence of 18 variables (sex, age, drug exposure, body weight, genetically determined enzyme activity, previous drug experience, personality [NEO-FFI, and trait anxiety in the State-Trait Anxiety Inventory, STAI-T], and mood before drug intake [Adjective Mood Rating Scale, AMRS]) on the peak autonomic and total subjective responses to MDMA (measured with visual analog scales [VAS], and the five Dimensions of Altered States of Consciousness scale [5D-ASC]). Multiple linear mixed effects models were fitted for each of the response variables. Results were adjusted for MDMA dose per bodyweight and corrected using the Benjamini-Hochberg procedure.
The variable which best predicted the responses to MDMA was the MDMA plasma concentration. It correlated with the mean arterial pressure as well as with ratings of “any drug” effects (p<0.05 and p<0.01, respectively). Subject’s openness to experiences as a trait measure was positively correlated with VAS ratings of “closeness”, and 5D-ASC ratings of “oceanic boundlessness” and visionary restructuralization” after MDMA (p<0.05, p<0.05, and p<0.01). NEO-FFI “neuroticism” and STAI “trait anxiety” positively correlated with 5D-ASC “dread of ego dissolution” (p<0.001 and p<0.01, respectively). Additionally, the acute response on the 5D-ASC subscale “anxiety” positively correlated with AMRS “anxiety-depressiveness” and “introversion” before drug intake (both p<0.05).
Although drug plasma concentration was the most important predictor of the acute response to MDMA, psychological factors such as trait openness to new experiences and state mood before drug intake also significantly predicted the subjective drug effects of MDMA. The results confirm that both pharmacological and non-pharmacological psychological factors play an important role in the anticipated subjective effects of MDMA, and could potentially be considered when using MDMA in psychiatric settings.