Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects
Borgwardt, S., Duthaler, U., Holze, F., Liechti, M. E., Müller, F., Vizeli, P.
This placebo-controlled, double-blind, cross-over case study (n=27) investigated the pharmacokinetics and subjective effects under controlled administration of a known oral LSD (100 μg) in healthy subjects (13 males and 14 females). The study showed that LSD produced high subjective “good drug effect” in almost all of the participants as compared to “bad drug effects” which were not found in every participant, confirming that anxiety is associated with higher LSD concentrations.
Abstract
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 (Cmax) values (range) of 1.7 (1.0-2.9) ng/mL were reached at a tmax (range) of 1.7 (1.0-3.4) hours after drug administration. The plasma half-life (t1/2) 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 Cmax values (range) of 0.11 (0.07-0.19) ng/mL were reached at a tmax (range) of 5 (3.2-8) hours. The t1/2 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. EC50 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.