A single 200 microgram dose of LSD increases several stress-related steroid hormones in the blood, particularly glucocorticoids like cortisol and corticosterone, in healthy adults. In a randomized, double-blind, placebo-controlled crossover study with 16 participants, LSD raised plasma levels of cortisol, cortisone, corticosterone, and 11-dehydrocorticosterone compared to placebo, with peak cortisol levels occurring about 2.5 hours after dosing. LSD also increased the androgen dehydroepiandrosterone but did not affect other androgens, progestogens, or mineralocorticoids. The rises in glucocorticoids closely tracked blood LSD concentrations and the intensity of the psychedelic experience, without signs of acute tolerance.
MDMA (ecstasy) but not methylphenidate (Ritalin) acutely alters several steroid hormones over 24 hours. In 16 healthy adults given single doses of MDMA (125 mg), methylphenidate (60 mg), both drugs together, or placebo on separate days, MDMA raised cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone, and tended to increase aldosterone, while leaving cortisone, DHEA, DHEAS, androstenedione, and testosterone unchanged. Methylphenidate alone did not affect any steroid levels and did not modify MDMA's effects. These results indicate that serotonin release, not dopamine or norepinephrine stimulation, drives acute activation of the hypothalamic-pituitary-adrenal axis by these drugs.