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Clin Pharmacokinet. 2017 Oct;56(10):1219-1230. doi: 10.1007/s40262-017-0513-9.

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects.

Author information

1
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Hebelstrasse 2, 4031, Basel, Switzerland.
2
Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
3
Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
4
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Hebelstrasse 2, 4031, Basel, Switzerland. matthias.liechti@usb.ch.

Abstract

BACKGROUND AND OBJECTIVE:

Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure-response relationship of oral LSD.

METHODS:

We analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling.

RESULTS:

Geometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2-1.9) and 3.1 (2.6-4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2-3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups.

CONCLUSIONS:

The present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related to changes in plasma concentrations over time, with no evidence of acute tolerance.

TRIAL REGISTRATION:

NCT02308969, NCT01878942.

KEYWORDS:

Autonomic Effect; Drug Effect; Lysergic Acid Diethylamide; Psilocybin; Subjective Effect

PMID:
28197931
PMCID:
PMC5591798
DOI:
10.1007/s40262-017-0513-9
[Indexed for MEDLINE]
Free PMC Article

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