Pharmacokinetics, pharmacodynamics and urinary recovery of oral lysergic acid diethylamide administration in healthy participants

AimsLysergic acid diethylamide (LSD) is currently investigated for several neurological and psychiatric illnesses. Various studies have investigated the pharmacokinetics and the pharmacokinetic-pharmacodynamic relationship of LSD in healthy participants, but data on urinary recovery and confirmatory studies are missing.MethodsThe present study characterized the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship and urinary recovery of LSD at doses of 85 and 170 & mu;g administered orally in 28 healthy participants. The plasma concentrations and subjective effects of LSD were continuously evaluated over a period of 24 h. Urine was collected during 3 time intervals (0-8, 8-16 and 16-24 h after LSD administration). Pharmacokinetic parameters were determined using compartmental modelling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modelling.ResultsMean (95% confidence interval) maximal LSD concentrations were 1.8 ng/mL (1.6-2.0) and 3.4 ng/mL (3.0-3.8) after the administration of 85 and 170 & mu;g LSD, respectively. Maximal concentrations were achieved on average after 1.7 h. Elimination half-lives were 3.7 h (3.4-4.1) and 4.0 h (3.6-4.4), for 85 and 170 & mu;g LSD, respectively. Only 1% of the administered dose was recovered from urine unchanged within the first 24 h, 16% was eliminated as 2-oxo-3-hydroxy-LSD. Urinary recovery was dose proportional. Mean (& PLUSMN;standard deviation) durations of subjective effects were 9.3 & PLUSMN; 3.2 and 11 & PLUSMN; 3.7 h, and maximal effects (any drug effects) were 77 & PLUSMN; 18% and 87 & PLUSMN; 13% after 85 and 170 & mu;g of LSD, respectively.ConclusionThe present novel study validates previous findings. LSD exhibited dose-proportional pharmacokinetics and first-order elimination kinetics and dose-dependent duration and intensity of subjective effects. LSD is extensively metabolized and shows dose-proportional urinary recovery.

Automated summary

This study investigated the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship, and urinary recovery of LSD in healthy participants. The results showed that LSD exhibits dose-proportional pharmacokinetics and first-order elimination kinetics, with the duration and intensity of its subjective effects being dose-dependent. The study also found that LSD is extensively metabolized and shows dose-proportional urinary recovery. Evaluation: 8 out of 10.