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Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects

Petra Strajhar, Yasmin Schmid, Evangelia Liakoni, Patrick C. Dolder, Katharina Rentsch, Denise V. Kratschmar, Alex Odermatt, Matthias E. Liechti

Journal of Neuroendocrinology February 6, 2016 DOI: 10.1111/jne.12374 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, placebo-controlled, cross-over study Peer reviewed
Sample size 16
Population Healthy subjects
Intervention LSD (200 μg)
Dose 200 μg
Topics LSD
Keywords Endocrinology Steroid Pharmacology
Citations 129
Key points LSD significantly increases plasma glucocorticoids, especially cortisol and corticosterone, in a manner closely linked to plasma LSD concentrations and psychotropic effects, without acute pharmacological tolerance.

Abstract

Lysergic acid diethylamide (LSD) is a serotonin 5‐hydroxytryptamine‐2A (5‐HT 2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double‐blind, placebo‐controlled, cross‐over study design. Plasma concentration–time profiles were determined for 15 steroids using liquid‐chromatography tandem mass‐spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11‐dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5–6 h and 1–3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD‐induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.

Comparable studies

Other randomized controlled trials on LSD, most cited first.

Study Year Design Participants
Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases 2014 Randomized controlled trial n = 12
Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users 1994 Double-blind, saline placebo-controlled, randomized study n = 12
Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) 2014 Double-blind, randomized, placebo-controlled, crossover study n = 16
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants 2018 Double-blind, randomized, counterbalanced, cross-over study n = 24
LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults 2016 Balanced-order, placebo-controlled study n = 19

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