The effect of MDMA on anterior pituitary hormones: a secondary analysis of a randomized placebo-controlled trial

3,4-Methylenedioxymethamphetamine (MDMA), a psychoactive substance, has been proposed as a novel provocation test for oxytocin deficiency. Limited evidence suggests that MDMA may also stimulate the anterior pituitary. Therefore, this analysis aimed to investigate the acute effect of MDMA on the anterior pituitary in healthy adults.

This secondary analysis utilized data from a double-blind, placebo-controlled, crossover, randomized trial. Healthy participants received a single oral dose of MDMA (100 mg) or placebo in random order. Plasma hormone levels of the anterior pituitary (adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), prolactin, growth hormone (GH)) and their peripheral endocrine glands (cortisol, free thyroxine (fT4), testosterone, and estradiol) were measured at baseline and 120 min after drug-intake. Plasma hormone changes following MDMA vs placebo were compared using the paired Wilcoxon test.

Fifteen healthy participants (median (IQR) age: 35 years (26, 48); 53% female) with a mean (SD) BMI of 23.2 kg/m2 (2.1) were included. MDMA stimulated the hypothalamic-pituitary-adrenal (HPA) axis, with plasma ACTH increasing from 12 ng/L (11, 15) at baseline to 38 ng/L (25, 59) at 120 min, resulting in a significant change of ACTH (P < 0.001). This was accompanied by a cortisol increase from 347 nmol/L (252, 409) to 566 nmol/L (457, 701), resulting in a significant change of cortisol (P = 0.006). Prolactin showed a mild change of 4 μg/L (-1, 12) (P = 0.062). No effects of MDMA were observed on the remaining anterior pituitary axes.

MDMA strongly activates the HPA axis, in addition to stimulating oxytocin, suggesting that MDMA may serve as a novel stimulation test for assessing the two pituitary axes simultaneously. Further validation in larger patient populations is necessary.