Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers

Autor: Emeline L. Maillet, Shlomi Raz, Daniel J. Goble, Charles D. Nichols, Erwin Krediet, Tim M. Williams, Robin L. Carhart-Harris, Luke T. J. Williams, Neiloufar Family
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Aging
Administration
Oral
Neurodegenerative
Pharmacology
Alzheimer's Disease
Neurodegenerative disease
Medical and Health Sciences
law.invention
Cognition
Randomized controlled trial
law
Medicine
5-HT2A
Lysergic acid diethylamide
Original Investigation
Psychiatry
Cross-Over Studies
Middle Aged
Healthy Volunteers
Clinical trial
Tolerability
6.1 Pharmaceuticals
Administration
Female
Drug
CNS
medicine.drug
Oral
Serotonin
Clinical Trials and Supportive Activities
Placebo
Dose-Response Relationship
Pharmacokinetics
Double-Blind Method
Clinical Research
Acquired Cognitive Impairment
Psychedelics
Reaction Time
Humans
Adverse effect
Aged
Inflammation
Dose-Response Relationship
Drug
business.industry
Prevention
Psychology and Cognitive Sciences
Neurosciences
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Evaluation of treatments and therapeutic interventions
Proprioception
Brain Disorders
Lysergic Acid Diethylamide
Immune system
Pharmacodynamics
Hallucinogens
Dementia
business
Alzheimer’s
Zdroj: Psychopharmacology
Psychopharmacology, vol 237, iss 3
ISSN: 1432-2072
0033-3158
Popis: Abstract Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A 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).
Databáze: OpenAIRE
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