Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants.

Abstract

"Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic-pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5days. Plasma levels of LSD and subjective effects were assessed up to 6hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151pg/mL (127-181), 279pg/mL (243-320), and 500pg/mL (413-607) after 5, 10, and 20µg LSD administration, respectively. Maximal concentrations were reached after 1.1hours. The mean elimination half-life was 2.7hours (1.5-6.2). The 5µg dose of LSD elicited no significant acute subjective effects. The 10µg dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1hours after 10µg LSD administration, peaked at 2.5hours, and ended at 5.1hours. The 20µg dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose-proportionally increased at doses as low as 5-20µg and decreased with a half-life of 3hours. The threshold dose of LSD base for psychotropic effects was 10µg.