Dataset Information

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

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 ?g, 10 ?g, and 20 ?g 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 ?g, 10 ?g, 20 ?g 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 ?g (n?=?12), 10 ?g (n?=?12), or 20 ?g (n?=?12) LSD. LSD plasma levels were undetectable for the 5 ?g group and peak blood plasma levels for the 10 ?g and 20 ?g 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 ?g, 10 ?g, and 20 ?g 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).

SUBMITTER: Family N

PROVIDER: S-EPMC7036065 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Family Neiloufar N Maillet Emeline L EL Williams Luke T J LTJ Krediet Erwin E Carhart-Harris Robin L RL Williams Tim M TM Nichols Charles D CD Goble Daniel J DJ Raz Shlomi S

Psychopharmacology 20191218 3

Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT<sub>2A</sub> receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease.<h4>Objective</h4>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 ...[more]

PMID: 31853557

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Project description:Background and objectiveLysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure-response relationship of oral LSD.MethodsWe analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling.ResultsGeometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2-1.9) and 3.1 (2.6-4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2-3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups.ConclusionsThe present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related to changes in plasma concentrations over time, with no evidence of acute tolerance.Trial registrationNCT02308969, NCT01878942.

Project description:BACKGROUND:Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, a cytokine essential for the formation, function and survival of osteoclasts. This study assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of single-dose denosumab (60 and 120 mg) in healthy Chinese volunteers. METHODS:This randomized (3:3:2), single-blind, placebo-controlled study enrolled healthy Chinese volunteers to receive single subcutaneous injection of denosumab 60 mg, 120 mg, or placebo. Study consisted of screening period (up to 21 days), treatment and assessment period (19 weeks), and an end-of-study visit (at week 26). Denosumab pharmacokinetics and pharmacodynamics parameters were estimated using non-compartmental analysis. Safety and tolerability were assessed throughout the study. RESULTS:A total of 63 volunteers received the study treatment and 62 (98.4%) completed the study. Denosumab serum concentrations peaked at around Day 10 with dose-proportional increase from 60 mg to 120 mg. The mean terminal half-life of denosumab 60 mg and 120 mg was 15 days and 26 days, respectively. The serum C-terminal cross-linking telopeptide of type I collagen concentration-time profiles were similar (>80% decrease within 5 days) between denosumab 60 mg and 120 mg groups. The most commonly reported adverse event (AE) was decreased blood calcium levels (denosumab 60 mg, n = 13; denosumab 120 mg, n = 13; placebo, n = 1); however only one volunteer had calcium level below the abnormality value of potential clinical importance and none of the volunteers developed symptoms of hypocalcemia. The majority of AEs were of mild to moderate intensity. There were no deaths, serious AEs, or withdrawal from study due to AEs. No clinically significant findings in vital signs or electrocardiogram were observed. CONCLUSIONS:Both denosumab 60 mg and 120 mg were well tolerated with no new safety concerns identified in healthy Chinese volunteers with similar pharmacokinetics and pharmacodynamics profiles to that of Caucasians. TRIAL REGISTRATION:ClinicalTrial.gov NCT02135640.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

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