This is the third publication of a four-part study. The double-blind, placebo-controlled study (n=23) found that 10 µg of LSD (vs 5µg) produced psychedelic (psychotropic) effects (even more so at 20µg). The peak effects were at 2.5 hours and ended at 5 hours.
Abstract of Pharmacokinetics and pharmacodynamics of LSD microdoses in healthy participants
“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 h after administration. Pharmacokinetic parameters were determined using compartmental modelling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modelling. 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 h. The mean elimination half-life was 2.7 h (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 h after 10 µg LSD administration, peaked at 2.5 h, and ended at 5.1 h. 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 h. The threshold dose of LSD base for psychotropic effects was 10 µg.”
Authors: Friederike Holze, Matthias E. Liechti, Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder, Eef L. Theunissen, Urs Duthaler, Amanda Feilding, Johannes G. Ramaekers & Kim P. C. Kuypers
Notes on Pharmacokinetics and pharmacodynamics of LSD microdoses in healthy participants
The same subjects were also studied by Hutten et al. (2020a), Ramaekers et al. (2020), and Hutten et al. (2020b).
The study is supported in part by the Beckley Foundation.
Summary of Pharmacokinetics and pharmacodynamics of LSD microdoses in healthy participants
Holze and colleagues begin by discussing the recent resurgence of interest in using LSD for therapeutic purposes and the growing popularity of “microdosing” – the practice of taking very low doses of LSD at regular intervals to improve cognitive function and mood. The authors note that while there is increasing interest in this practice, little is known about the effects of very low doses of LSD, and more data are needed to determine specific doses that do not produce subjective effects.
The researchers explain that previous controlled studies using defined very low doses of LSD have provided limited pharmacokinetic data, precluding definitions of all pharmacokinetic parameters and pharmacokinetic-dynamic modeling. They highlight that in one recent Phase I trial, plasma levels of LSD could not be determined after a 5 μg dose due to low sensitivity of the analytical assay. Other studies have reported dose-dependent acute drug effects of LSD but did not obtain pharmacokinetic data.
Given these gaps in knowledge, Holze and colleagues designed the present study to assess the pharmacokinetics and acute effects of LSD and pharmacokinetic-effect relationships at doses of 5, 10, and 20 μg LSD base and placebo in 23 healthy subjects using a sensitive analytical method. They note that 13 μg of LSD tartrate contains 10 μg of LSD base, providing context for comparing their results to previous studies.
Methods
Study Design
Find this paper
https://doi.org/10.1002/cpt.2057
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Cite this paper (APA)
Holze, F., Liechti, M. E., Hutten, N. R., Mason, N. L., Dolder, P. C., Theunissen, E. L., ... & Kuypers, K. P. (2021). Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide microdoses in healthy participants. Clinical Pharmacology & Therapeutics, 109(3), 658-666.
Study details
Compounds studied
LSD
Topics studied
Microdosing
Neuroscience
Study characteristics
Original Re-analysis
Placebo-Controlled
Double-Blind
Within-Subject
Randomized
Participants
23
Humans
Authors
Authors associated with this publication with profiles on Blossom
Natasha MasonNatasha Mason is interested in elucidating the neurobiological and cognitive mechanisms of (psychedelic) drugs by utilizing multimodal study designs, with a particular focus on substances that may hold therapeutic value.
Matthias Liechti
Matthias Emanuel Liechti is the research group leader at the Liechti Lab at the University of Basel.
Amanda Feilding
Amanda is the Founder and Director of the Beckley Foundation. She's called the 'hidden hand' behind the renaissance of psychedelic science, and her contribution to global drug policy reform has also been pivotal and widely acknowledged.
Johannes Ramaekers
Johannes Ramaekers is a professor at Maastricht University his work focuses on behavioral toxicology of drugs and combines methods from psychopharmacology, forensic toxicology and neuroscience to determine drug-induced changes in human performance. Some of this research is done with DMT.
Kim Kuypers
Kim Kuypers is a researcher at Maastricht University. Her work is concerned with understanding the neurobiology underlying flexible cognition, empathy, and well-being. One of the main ways she does is with the use of psychedelics.
Institutes
Institutes associated with this publication
Beckley FoundationThe Beckley Foundation is one of the leading voices that has spurred the scientific renaissance of psychedelics research. Led by Amanda Fielding, the NGO funds research and engages with politicians.
Maastricht University
Maastricht University is host to the psychopharmacology department (Psychopharmacology in Maastricht) where various researchers are investigating the effects of psychedelics.
University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.
Compound Details
The psychedelics given at which dose and how many times
LSD 5 - 20μg | 1x
Linked Research Papers
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