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

This Phase I, double-blind, placebo-controlled, randomized study (n=48) indicates that LSD administration (tested up to 20µg) didn’t produce any negative effects for healthy older participants (age 63).

Abstract

Abstract Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signalling, 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 related 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).

Authors: Neiloufar Family, Emeline L. Maillet, Luke T. J. Williams, Erwin Krediet, Robin L. Carhart-Harris, Tim M. Williams, Charles D. Nichols, Daniel J. Goble & Shlomi Raz

Notes

This paper was included in a systematic review on microdosing psychedelics by Ona & Bouso (2020).

This paper used the same participants/data as Yanakieva et al (2018).

Study details

Compounds studied
LSD

Topics studied
Safety Healthy Subjects Microdosing

Study characteristics
Placebo-Controlled Double-Blind Randomized

Participants
48 Humans

Authors

Authors associated with this publication with profiles on Blossom

Erwin Krediet
Erwin Krediet is a PhD candidate at Leiden University Medical Center and Psychologist/Researcher at ARQ National Psychotrauma Centre. He also volunteers on the program team of ICPR.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

Charles D. Nichols
Charles D. Nichols is a professor of Pharmacology at LSU Health Sciences Center in New Orleans and sponsored researcher at Eleusis.

Institutes

Institutes associated with this publication

Eleusis
Eleusis is a clinical-stage life sciences company that studies and develops psychedelic drugs for therapeutic use. Since 2013 the company has been researching psychedelics and is now developing ELE-Psilo (psilocybin) for depression that is in Phase I.

Compound Details

The psychedelics given at which dose and how many times

LSD 5 - 20
μg | 6x

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Linked Clinical Trial

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