Seibert · Neuroendocrinology 2014 · randomized placebo-controlled crossover trial · n=16

Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

Cited 52 times in the scientific literature.

Level 2 - randomized trial

Randomized, placebo-controlled crossover clinical trial

PubMed 24903002 · doi:10.1159/000364879 · record verified 2026-08-31

What was done

Sixteen healthy participants (8 men, 8 women) received single oral doses of MDMA (125 mg), methylphenidate (60 mg), MDMA combined with methylphenidate, and placebo across 4 separate test days in a randomized crossover design. Plasma concentrations of ten circulating steroids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, DHEA, DHEAS, androstenedione, and testosterone) were repeatedly quantified up to 24 hours using liquid chromatography-tandem mass spectrometry.

What was found

The abstract reports directional outcomes without exact numerical values or effect sizes. MDMA significantly elevated plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone, alongside the sum of cortisol plus cortisone and the cortisol/cortisone ratio. MDMA also produced a moderate trend toward increased aldosterone, but had no effect on cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate had no detectable effect on any measured steroid levels and did not modify the steroid response to MDMA.

Why it matters

These findings demonstrate that acute pharmacologic activation of the hypothalamic-pituitary-adrenal axis by psychostimulants is mediated predominantly by serotonergic mechanisms rather than dopamine or norepinephrine release alone.

Limits

The study had a very small sample size (n = 16) and evaluated only single acute doses in healthy young volunteers. The abstract does not provide exact baseline or peak steroid values, confidence intervals, or p-values.

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