Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers
Psychopharmacology – December 18, 2019
Source: OpenAlex
Summary
Lysergic acid diethylamide (LSD), a chemical synthesis and alkaloid, holds promise for treating neuroinflammation. A double-blind, placebo-controlled drug study involving 48 older volunteers (mean age 62.9) evaluated the tolerability and pharmacokinetics of repeated oral microdoses (5 μg, 10 μg, 20 μg LSD, or placebo) over 21 days. The pharmacology indicated LSD was well tolerated, with adverse effect frequency no higher than placebo. Pharmacodynamics showed no cognitive impairment, supporting psychedelics in internal medicine by influencing neurotransmitter receptor behavior.
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).