Healthy VolunteersMedicinal Chemistry & Drug DevelopmentLSD

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

This study characterised the pharmacokinetics of a novel oral LSD solution (100 μg) in 27 healthy subjects, finding first‑order elimination with a geometric mean Cmax ≈1.7 ng/mL at 1.7 h, t1/2 ≈3.6 h, measurable O‑H‑LSD but not nor‑LSD, and no sex differences. The subjective effects lasted about 8.5 h with peak effects at ≈2.5 h and were closely associated with plasma concentrations (EC50 ≈1.0 ng/mL for “good” and ≈1.9 ng/mL for “bad” effects).

Authors

  • Patrick Vizeli
  • Stefan Borgwardt
  • Felix Müller

Published

British Journal of Clinical Pharmacology
individual Study

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.

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

Introduction

Earlier research has produced only limited and fragmentary pharmacokinetic (PK) data for lysergic acid diethylamide (LSD) in humans, with small intravenous studies and short, sparsely sampled oral studies leaving uncertainty about standardised exposure–time profiles. Holze and colleagues note that previous oral PK work by their group used a capsule formulation that lacked documented long-term stability, creating a need for well characterised, stable formulations for both experimental and clinical use. This study set out to characterise the PK of a newly manufactured, analytically confirmed oral LSD solution intended for clinical research and patient use. Secondary aims were to describe acute subjective effects, link those effects to plasma concentrations using pharmacokinetic–pharmacodynamic (PK/PD) modelling to derive EC50 values (the concentration producing half-maximal effect), to quantify the main metabolites 2-oxo-3-hydroxy-LSD (O-H-LSD) and N-desmethyl-LSD (nor-LSD) in plasma, and to compare exposure from the novel solution with previously tested capsule data.

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Study Details

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