Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study.
Denis Arikci, Friederike Holze, Lorenz Mueller, Patrick Vizeli, Deborah Rudin, Dino Luethi, Cédric M. Hysek, Matthias E. Liechti
Clinical Pharmacology & Therapeutics May 26, 2025 DOI: 10.1002/cpt.3726 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, five-period crossover trial Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy participants |
| Interventions | Ethanolic drinking solution of LSD base watery drinking solution of LSD tartrate rapid dissolvable tablet of LSD base intravenous formulation of LSD tartrate corresponding placebos |
| Dose | ~80 μg freebase equivalent |
| Duration | Up to 24 hours |
| Topics | LSD |
| Keywords | Psychedelics Pharmacology Drug absorption Medical research Mental health treatment |
| Citations | 6 |
| Key findings | Oral LSD base and tartrate formulations are bioequivalent with an absolute oral bioavailability of 80%. |
Abstract
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.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 7
- The 3D-ASCr scale: A revalidation of the core dimensions of the Altered States of Consciousness Rating Scale 5D(11)-ASC for psychedelic research. Journal of Psychopharmacology December 26, 2025
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- DT120 (MM120): a single-dose orally disintegrating formulation of lysergide tartrate for generalized anxiety disorder Expert Review of Neurotherapeutics October 8, 2026
- Effects of repeated low-dose LSD on neuropsychological functioning in adults with ADHD: a randomized placebo-controlled study Psychopharmacology June 20, 2026
- Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems. ACS Pharmacology & Translational Science June 12, 2026
and 2 more in the library
Cites 38
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
and 33 more in the library