Pharmacokinetics, pharmacodynamics and urinary recovery of oral lysergic acid diethylamide administration in healthy participants.
Friederike Holze, Livio Erne, Urs Duthaler, Matthias E. Liechti
British Journal of Clinical Pharmacology 2024 DOI: 10.1111/bcp.15887 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pharmacokinetic-pharmacodynamic study Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy participants |
| Intervention | Lysergic acid diethylamide (LSD) |
| Dose | 85 and 170 μg |
| Duration | 24-hour monitoring period with urine collection at 0-8, 8-16, and 16-24 hours |
| Topics | LSD |
| Keywords | Pkpd Pharmacodynamics Pharmacokinetics Urinary recovery Psychedelics Pharmacology Drug metabolism Clinical research |
| Citations | 12 |
| Key points | LSD exhibits dose-proportional pharmacokinetics, first-order elimination, extensive metabolism, and dose-dependent duration and intensity of subjective effects. |
Abstract
Lysergic acid diethylamide (LSD) is currently investigated for several neurological and psychiatric illnesses. Various studies have investigated the pharmacokinetics and the pharmacokinetic-pharmacodynamic relationship of LSD in healthy participants, but data on urinary recovery and confirmatory studies are missing. The present study characterized the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship and urinary recovery of LSD at doses of 85 and 170 μg administered orally in 28 healthy participants. The plasma concentrations and subjective effects of LSD were continuously evaluated over a period of 24 h. Urine was collected during 3 time intervals (0-8, 8-16 and 16-24 h after LSD 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 1.8 ng/mL (1.6-2.0) and 3.4 ng/mL (3.0-3.8) after the administration of 85 and 170 μg LSD, respectively. Maximal concentrations were achieved on average after 1.7 h. Elimination half-lives were 3.7 h (3.4-4.1) and 4.0 h (3.6-4.4), for 85 and 170 μg LSD, respectively. Only 1% of the administered dose was recovered from urine unchanged within the first 24 h, 16% was eliminated as 2-oxo-3-hydroxy-LSD. Urinary recovery was dose proportional. Mean (±standard deviation) durations of subjective effects were 9.3 ± 3.2 and 11 ± 3.7 h, and maximal effects (any drug effects) were 77 ± 18% and 87 ± 13% after 85 and 170 μg of LSD, respectively. The present novel study validates previous findings. LSD exhibited dose-proportional pharmacokinetics and first-order elimination kinetics and dose-dependent duration and intensity of subjective effects. LSD is extensively metabolized and shows dose-proportional urinary recovery.
Comparable studies
Other experimental studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants | 2016 | Experimental study | |
| Crystal structure of an LSD-bound human serotonin receptor | 2017 | Experimental study with structural biology and molecular dynamics simulations | |
| Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin | 1968 | Experimental study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients | 1973 | Experimental study | n = 60 |
Citations in the library
Cited by 11
- Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile Biological Psychiatry: Cognitive Neuroscience and Neuroimaging February 1, 2024
- Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine. Neuropsychopharmacology June 1, 2024
- Stimulant and hallucinogenic novel psychoactive substances; an update Expert Review of Clinical Pharmacology November 2, 2023
- Psychedelics for the Treatment of Obsessive–Compulsive Disorder: Efficacy and Proposed Mechanisms The International Journal of Neuropsychopharmacology November 29, 2024
- LSD's rapid antidepressant effects are modulated by 5-HT2B receptors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 16, 2025
and 6 more in the library
Cites 20
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 15 more in the library