Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects

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 mu g) 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(infinity) was 13 (7.1-28) ng center dot 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(infinity) values of O-H-LSD were 5.2 (2.6-21) hours and 1.7 (0.85-4.3) ng center dot 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.