Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects
British Journal of Clinical Pharmacology – March 19, 2019
Source: OpenAlex
Summary
LSD's effects can last up to 12.8 hours, with peak experiences occurring around 2.5 hours after ingestion. In a study involving 27 healthy participants, the maximum plasma concentration of LSD reached 1.7 ng/mL within approximately 1.7 hours, while its half-life was found to be 3.6 hours. The metabolite O-H-LSD peaked at 0.11 ng/mL after about 5 hours. Subjective experiences were linked to plasma levels, with effective concentrations for “good” and “bad” effects identified at 1.0 ng/mL and 1.9 ng/mL, respectively.
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 ( 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.