Pharmacokinetics, pharmacodynamics and urinary recovery of oral lysergic acid diethylamide (LSD) administration in healthy participants
Duthaler, U., Erne, L., Holze, F., Liechti, M. E.
This pharmacokinetic study (n=28) investigated the effects of oral LSD doses of 85 and 170 μg on healthy participants over 24 hours. The results showed mean maximal LSD concentrations of 1.8 ng/ml and 3.4 ng/ml for the respective doses, reaching peak concentrations after approximately 1.7 hours. Elimination half-lives were between 3.7 and 4.0 hours. Only 1% of LSD was found unchanged in urine within 24 hours, while 16% was eliminated as 2-oxo-3-hydroxy-LSD. Subjective effects lasted between 9.3 and 11 hours, with intensity peaking at 77% and 87% for the two doses.
Abstract
Aim Lysergic 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.Method The present study characterized the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship, and urinary recovery of LSD at doses of 85 and 170 μg administered orally in 28 healthy participants. The plasma concentrations and subjective effects of LSD were continuously evaluated over a period of 24 hours. Urine was collected during three time-intervals (0-8, 8-16, and 16-24h after LSD administration). Pharmacokinetic parameters were determined using compartmental modeling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling.Results Mean (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 μg LSD, respectively. Maximal concentrations were achieved on average after 1.7 h. Elimination half-lives were 3.7h (3.4-4.1) and 4.0h (3.6-4.4), for 85 and 170 μg LSD, respectively. Only 1% of the administered dose was recovered from urine unchanged within the first 24 hours, 16% was eliminated as 2-oxo-3-hydroxy-LSD (O-H-LSD). Urinary recovery was dose-proportional. Mean (±SD) durations of subjective effects were 9.3±3.2 h and 11±3.7 h, and maximal effects (“any drug” effects) were 77%±18% and 87%±13% after 85 and 170 μg of LSD, respectively.Conclusion The 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.