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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. [ABSTRACT FROM AUTHOR]

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 (>0.1 ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean ± SD: 4.5 ± 1.4 ng/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. [ABSTRACT FROM AUTHOR]

Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of the present study is to develop a quantitative turboflow LC-MS/MS method that can be used for rapid quantification of LSD and its mainmetabolite 2-oxo- 3-hydroxy LSD (O-H-LSD) in serum and urine in emergency toxicological cases without time-consuming extraction steps. The method was developed on an ion-trap LC-MS/MS instrument coupled to a turbulent-flow extraction system. The validation data showed no significant matrix effects and no ion suppression has been observed in serum and urine. Mean intraday accuracy and precision for LSD were 101 and 6.84 %, in urine samples and 97.40 and 5.89 % in serum, respectively. For O-H-LSD, the respective values were 97.50 and 4.99 % in urine and 107 and 4.70 % in serum. Mean interday accuracy and precision for LSD were 100 and 8.26% in urine and 101 and 6.56 % in serum, respectively. For O-HLSD, the respective values were 101 and 8.11 % in urine and 99.8 and 8.35 % in serum, respectively. The lower limit of quantification for LSD was determined to be 0.1 ng/ml. LSD concentrations in serum were expected to be up to 8 ng/ml. 2- Oxo-3-hydroxy LSD concentrations in urine up to 250 ng/ml. The new method was accurate and precise in the range of expected serum and urine concentrations in patients with a suspected LSD intoxication. Until now, the method has been applied in five cases with suspected LSD intoxication where the intake of the drug has been verified four times with LSD concentrations in serum in the range of 1.80–14.70 ng/ml and once with a LSD concentration of 1.25 ng/ml in urine. In serum of two patients, the O-H-LSD concentration was determined to be 0.99 and 0.45 ng/ml. In the urine of a third patient, the O-H-LSD concentration was 9.70 ng/ml. [ABSTRACT FROM AUTHOR]

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 (>0.1 ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean±SD: 4.5±1.4 ng/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., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)