Pharmacokinetics and concentration-effect relationship of oral LSD in humans
Dolder, P. C., Haschke, M., Liechti, M. E., Rentsch, K. M., Schmid, Y.
This double-blind, placebo-controlled, within-subjects study (n=16) evaluated the pharmacokinetic profile of oral LSD (200 μg) in humans. The analysis found that the acute subjective and sympathomimetic effects of LSD lasted for up to 12 hours and were closely linked to the plasma concentrations over time and showed no acute tolerance. This is the first such study and can act as a potential reference for the assessment of intoxication with LSD.
Abstract
Background: The pharmacokinetics of oral lysergic acid diethylamide are unknown despite its common recreational use and renewed interest in its use in psychiatric research and practice.Methods: We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of lysergic acid diethylamide and its main metabolite after administration of a single oral dose of lysergic acid diethylamide (200 μg) in 8 male and 8 female healthy subjects.Results: Plasma lysergic acid diethylamide concentrations were quantifiable (>0.1ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean±SD: 4.5±1.4ng/mL) were reached (median, range) 1.5 (0.5-4) hours after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6±0.9 hours up to 12 hours and slower elimination thereafter with a terminal half-life of 8.9±5.9 hours. One percent of the orally administered lysergic acid diethylamide was eliminated in urine as lysergic acid diethylamide, and 13% was eliminated as 2-oxo-3-hydroxy-lysergic acid diethylamide within 24 hours. No sex differences were observed in the pharmacokinetic profiles of lysergic acid diethylamide. The acute subjective and sympathomimetic responses to lysergic acid diethylamide lasted up to 12 hours and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance.Conclusions: These first data on the pharmacokinetics and concentration-effect relationship of oral lysergic acid diethylamide are relevant for further clinical studies and serve as a reference for the assessment of intoxication with lysergic acid diethylamide.