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Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects
Author(s) -
Holze Friederike,
Duthaler Urs,
Vizeli Patrick,
Müller Felix,
Borgwardt Stefan,
Liechti Matthias E.
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13918
Subject(s) - pharmacokinetics , lysergic acid diethylamide , geometric mean , placebo , oral administration , pharmacology , medicine , chemistry , mathematics , statistics , receptor , alternative medicine , pathology , serotonin
Aims The aim of the present study was to characterize the pharmacokinetics and exposure–subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients. Method LSD (100 μg) was administered in 27 healthy subjects using a placebo‐controlled, double‐blind, cross‐over design. Plasma levels of LSD, nor‐LSD, and 2‐oxo‐3‐hydroxy‐LSD (O‐H‐LSD) and subjective drug effects were assessed up to 11.5 hours. Results First‐order elimination kinetics were observed for LSD. Geometric mean maximum concentration ( C max ) values (range) of 1.7 (1.0–2.9) ng/mL were reached at a t max (range) of 1.7 (1.0–3.4) hours after drug administration. The plasma half‐life ( t 1/2 ) was 3.6 (2.4–7.3) hours. The AUC ∞ was 13 (7.1–28) ng·h/mL. No differences in these pharmacokinetic parameters were found between male and female subjects. Plasma O‐H‐LSD but not nor‐LSD (< 0.01 ng/mL) concentrations could be quantified in all subjects. Geometric mean O‐H‐LSD C max values (range) of 0.11 (0.07–0.19) ng/mL were reached at a t max (range) of 5 (3.2–8) hours. The t 1/2 and AUC ∞ values of O‐H‐LSD were 5.2 (2.6–21) hours and 1.7 (0.85–4.3) ng·h/mL, respectively. The subjective effects of LSD lasted (mean ± SD) for 8.5 ± 2.0 hours (range: 5.3–12.8 h), and peak effects were reached 2.5 ± 0.6 hours (range 1.6–4.3 h) after drug administration. EC 50 values were 1.0 ± 0.5 ng/mL and 1.9 ± 1.0 ng/mL for “good” and “bad” subjective drug effects, respectively. Conclusion The present study characterized the pharmacokinetics of LSD and its main metabolite O‐H‐LSD. The subjective effects of LSD were closely associated with changes in plasma concentrations over time.