Pharmacokinetics and subjective effects of 1P-LSD in humans after oral and intravenous administration.

1-Propanoyl-lysergic acid diethylamide (1P-LSD) appeared as a non-controlled alternative to LSD a few years ago. Although evidence is beginning to emerge from in vitro and animal studies that 1P-LSD might serve as a prodrug for LSD, an equivalent evaluation in humans is unavailable. Controlled oral and intravenous self-administrations of 100 μg 1P-LSD hemitartrate are reported in two human volunteers followed by analyses of urine and serum samples using a fully validated LC-MS/MS method. Psychometric evaluations included assessment of selected subjective drug effects and administration of the Five-Dimensions of Altered States of Consciousness rating scale (5D-ASC). In serum and urine, oral administrations of 1P-LSD only led to the detection of LSD reflecting biphasic elimination with a terminal elimination half-life of approx. t1/2 = 6.4 h. 1P-LSD could be detected for only up to 4.16 h in serum and 2.7 h in urine following intravenous administration, whereas LSD was detected in all serum samples (last sampling after approx. 24 h) and up to 80 h in urine. LSD showed first order elimination kinetics with an approx. t1/2 = 5.7 h, whereas 1P-LSD showed a rapid decrease in concentration within the first hour followed by a slower decrease, most probably due to hydrolysis. The bioavailability of LSD after oral ingestion of 1P-LSD was close to 100%. The psychosensory effects of 1P-LSD and their time course were comparable to those seen after uptake of LSD in other studies which further supports the prodrug hypothesis. The 5D-ASC scores were higher after oral compared with intravenous administration of 1P-LSD.