Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants
Clinical Pharmacology & Therapeutics – September 25, 2020
Source: OpenAlex
Summary
Lysergic acid diethylamide "microdosing" has a psychotropic threshold of 10 µg. A placebo-controlled Pharmacology study with 23 healthy participants explored the Pharmacokinetics and Pharmacodynamics of this synthetic alkaloid. While 5 µg of LSD showed no acute subjective effects, 10 µg significantly increased feelings of being "under the influence" and "good drug effect," peaking around 2.5 hours. LSD concentrations dose-proportionally increased, with a 2.7-hour elimination half-life. These Psychedelics and Drug Studies findings are crucial for developing LSD as a potential Medicine, informing Complementary and Alternative Medicine Studies.
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 20 µg) and placebo were administered in a double‐blind, randomized, placebo‐controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours 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 151 pg/mL (127–181), 279 pg/mL (243–320), and 500 pg/mL (413–607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half‐life was 2.7 hours (1.5–6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of “under the influence” and “good drug effect” compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg 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 5–20 µg and decreased with a half‐life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg.