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 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. 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.

DOI: 10.1111/bcp.13918

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