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

A single oral dose of MDMA (100 mg) strongly activates the hypothalamic-pituitary-adrenal (HPA) axis in healthy adults. Plasma ACTH increased from 12 ng/L to 38 ng/L and cortisol from 347 nmol/L to 566 nmol/L within 120 minutes. Prolactin showed a mild, non-significant change. MDMA did not affect other anterior pituitary hormones (TSH, LH, GH) or their peripheral hormones (fT4, testosterone, estradiol). The findings suggest MDMA may serve as a novel stimulation test for simultaneously assessing the HPA axis and oxytocin systems, but further validation in larger populations is needed.

Study at a glance

Abstract

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, estradiol) were measured at baseline and 120 minutes after drug-intake. Plasma hormone changes following MDMA vs placebo were compared using 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 minutes, 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.