Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants
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
Clinical Pharmacology & Therapeutics September 25, 2020 DOI: 10.1002/cpt.2057 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy participants |
| Intervention | LSD base |
| Dose | 5, 10, and 20 µg |
| Duration | Single dose, assessed up to 6 hours after administration |
| Topics | LSD |
| Keywords | Pharmacodynamics Pharmacokinetics Pharmacology |
| Citations | 63 |
| Key findings | The threshold dose of LSD base for psychotropic effects was 10 µg, with dose-proportional increases in plasma concentration and a half-life of about 3 hours. |
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.
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 60
- Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study European Neuropsychopharmacology October 17, 2020
- Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants Clinical Pharmacology & Therapeutics December 12, 2022
- The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955–2021) and recommendations for the field Neuroscience & Biobehavioral Reviews May 21, 2022
- Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants The International Journal of Neuropsychopharmacology November 4, 2022
- Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study. Addiction Biology February 1, 2022
and 55 more in the library
Cites 26
- Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases The Journal of Nervous and Mental Disease March 4, 2014
- Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Journal of Psychopharmacology March 8, 2012
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
- Response of cluster headache to psilocybin and LSD Neurology June 26, 2006
- Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects Neuropsychopharmacology November 16, 2019
and 21 more in the library