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

1P-LSD, a non-controlled alternative to LSD, acts as a prodrug that converts almost entirely into LSD in the human body. In two volunteers, oral and intravenous doses of 100 μg 1P-LSD were administered. After oral intake, only LSD was detected in serum and urine, with a terminal elimination half-life of about 6.4 hours. Intravenous 1P-LSD was detectable for only a few hours, while LSD persisted much longer. The bioavailability of LSD from oral 1P-LSD was nearly 100%. Subjective drug effects and altered states of consciousness scores were comparable to those from LSD, supporting the prodrug hypothesis. Oral administration produced higher 5D-ASC scores than intravenous.

Study at a glance

Abstract

Abstract 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. t 1/2 = 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. t 1/2 = 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.