This randomized, double-blind, placebo-controlled crossover study (n=20) tests the bioequivalence and oral bioavailability of LSD base and tartrate in various formulations (ethanolic solution, watery solution, dissolvable tablet, and IV). All oral formulations were bioequivalent with 80% absolute oral bioavailability. IV LSD produced stronger subjective effects, including more ego dissolution and anxiety.
Abstract of Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study
“Lysergic acid diethylamide (LSD) is currently being investigated as a potential treatment for psychiatric and neurological disorders. Different LSD formulations (base or tartrate, oral or intravenous) are being used. Unclear is whether LSD base and tartrate pharmacokinetics are equivalent. Additionally, LSD’s absolute oral bioavailability is unknown. Therefore, we tested the bioequivalence of different oral LSD base and tartrate formulations and defined LSD’s absolute oral bioavailability at a dose of ~80 μg freebase equivalent. We used a randomized, double-blind, placebo-controlled, five-period crossover design in 20 healthy participants to investigate an ethanolic drinking solution of LSD base, a watery drinking solution of LSD tartrate, a rapid dissolvable tablet of LSD base, an intravenous formulation of LSD tartrate, and corresponding placebos. We assessed pharmacokinetic parameters and acute subjective, autonomic, and adverse effects up to 24 hours. All oral formulations were bioequivalent, with the ethanolic base solution as a reference. The area under the concentration–time curve from zero to infinity and maximum plasma concentration were within a 90% confidence interval of 80–125%. The absolute bioavailability of oral LSD was 80% and similar for all tested formulations. Overall, the oral formulations showed comparable pharmacokinetic and pharmacodynamic parameters. Intravenous LSD administration produced higher “any drug effect,” “good drug effect,” and “ego dissolution” compared with oral LSD tartrate, more “anxiety” compared with all oral formulations, and more “nausea” and “bad drug effect” compared with oral LSD base and tartrate. In conclusion, dosing with LSD base and tartrate can be considered bioequivalent with high and similar oral bioavailability.”
Authors: Denis Arikci, Friederike Holze, Lorenz Mueller, Patrick Vizeli, Deborah Rudin, Dino Luethi, Cedric M. Hysek & Matthias E. Liechti
Summary of Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study
Lysergic acid diethylamide (LSD) is a serotonergic psychedelic currently under investigation for various psychiatric and neurological conditions. Its mechanism of action involves agonism of the 5-HT2A receptor, which is central to the altered states of consciousness it induces. Recent regulatory recognition includes a Breakthrough Therapy designation for generalised anxiety disorder. LSD is most commonly administered as either a freebase or tartrate salt, with the latter being more prevalent in recreational use due to its water solubility and stability. Despite this, clinical research has often used the base form, primarily in capsules or ethanolic solutions. There is uncertainty over whether LSD base and tartrate produce equivalent pharmacokinetics and pharmacodynamics when dosed equivalently. Additionally, LSD’s absolute oral bioavailability has only been estimated indirectly. Arikci and colleagues conducted a study to directly compare different oral formulations of LSD and determine its absolute oral bioavailability using intravenous administration as a reference.
Methods
Study Design
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https://doi.org/10.1002/cpt.3726
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Cite this paper (APA)
Arikci, D., Holze, F., Mueller, L., Vizeli, P., Rudin, D., Luethi, D., ... & Liechti, M. E. Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double‐Blind, Placebo‐Controlled, Crossover Study. Clinical Pharmacology & Therapeutics.
Study details
Compounds studied
LSD
Topics studied
Healthy Subjects
Safety
Study characteristics
Original
Placebo-Controlled
Double-Blind
Within-Subject
Randomized
Participants
20
Humans
Institutes
Institutes associated with this publication
University of BaselThe 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 80 μg | 4xLinked Clinical Trial
LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy SubjectsThe present study will compare equivalent doses of LSD base in ethanol orally, LSD tartrate in water administered orally, LSD base in an orodispersible film administered orally and LSD tartrate in water administered intravenously, as well as a placebo using a double-blind, randomized, counterbalanced crossover design in healthy participants.