Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers
Neiloufar Family, Émeline L. Maillet, Luke T. J. Williams, Erwin Krediet, Robin Carhart‐Harris, Tom A. Williams, Charles D. Nichols, Daniel J. Goble, Shlomi Raz
Psychopharmacology December 18, 2019 DOI: 10.1007/s00213-019-05417-7 via OpenAlex
Summary
AI-generated from the abstractRepeated low doses of LSD are safe and well tolerated in older adults. In a double-blind, placebo-controlled trial, 48 healthy volunteers aged around 63 received either 5, 10, or 20 micrograms of LSD or a placebo every four days for three weeks. LSD was undetectable in the blood at the 5 microgram dose, while peak levels for higher doses occurred within 30 minutes. Adverse events were no more frequent than with placebo, and tests of cognition, balance, and proprioception showed no impairment. These results support further clinical development of low-dose LSD for treating or preventing Alzheimer's disease.
Study at a glance
| Characteristics | Phase 1 double-blind, placebo-controlled, randomized study Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Older healthy volunteers (mean age 62.9 years) |
| Intervention | LSD |
| Dose | 5 μg, 10 μg, 20 μg |
| Duration | 21-day period (six doses every 4 days) |
| Topics | LSD |
| Keywords | Tolerability Pharmacokinetics Placebo Pharmacodynamics |
| Citations | 142 |
| Key finding | Orally administered 5, 10, and 20 μg LSD every fourth day over 21 days is safe and well tolerated in older adults, with no impairment in cognition, balance, or proprioception. |
Abstract
Abstract Abstract Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT 2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease. Objective This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response. Methods This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days). Results Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo ( n = 12), 5 μg ( n = 12), 10 μg ( n = 12), or 20 μg ( n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment. Conclusions Our results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer’s disease (AD).