This Phase I study explored the safety, tolerability, pharmacokinetics, and pharmacodynamics of low doses of Lysergic Acid Diethylamide (LSD) ranging from 50 µg to 100 µg. The study consisted of two parts:
Part 1: An open-label dose-escalation study involving hallucinogen non-naïve subjects with significant prior experience with hallucinogens. Each subject received a single dose of LSD (50, 75, or 100 µg) and underwent assessments at different time points, including cognitive tasks and pharmacokinetic (PK) analysis.
Part 2: A double-blind, placebo-controlled, randomized, crossover study in hallucinogen naïve subjects. Participants were assigned to cohorts and received either placebo followed by 75 µg LSD or LSD 50 µg followed by 75 µg, with dosing separated by at least 7 days. Assessments included cognitive tasks and follow-ups at specific intervals.
Participants: A total of 32 subjects were enrolled, aged 21 to 65, meeting inclusion/exclusion criteria related to health, drug exposure, and psychiatric history.
Interventions: Participants were administered LSD doses ranging from 50 µg to 100 µg, and placebo in a crossover design. The study measured adverse events, plasma concentration profiles, and subjective drug effects using various scales and questionnaires.
Outcomes: The primary outcome focused on assessing adverse events by frequency, safety, and tolerability of LSD. Secondary outcomes included pharmacokinetic measures (AUC 0-24h, Cmax, Tmax), subjective drug effects, altered states of consciousness, and ego dissolution.
The study spanned from October 2015 to July 2017 and was conducted at PAREXEL, Early Phase Clinical Unit in London. It was sponsored by Eleusis Therapeutics.
Trial Details
This study with low-dose LSD comprised 2 substudies in healthy subjects. Subjects who met all inclusion and no exclusion criteria provided written informed consent. Part 1 was an open-label dose-escalation study in hallucinogen non-naïve subjects with significant prior experience with hallucinogens, during which each subject received a single dose of LSD: 50, 75, or 100 µg. Part 2 was a double blind, placebo controlled, randomised, crossover study in hallucinogen naïve subjects with no prior experience with hallucinogens in the last 7 years, during which each subject was assigned to 1 of 8 cohorts and then randomly assigned to receive single doses of LSD 50 µg followed by 75 µg, or placebo followed by 75 µg, with dosing separated by at least 7 days. Subjects were followed up on the day after each dosing, and 1 week and 1 month after the last dose of study treatment. A total of 32 subjects were enrolled.NCT Number NCT05674669
Sponsors & Collaborators
EleusisEleusis 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.
Papers
Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept studyThis trial (n=32) assessed the safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy adults within a novel intervention paradigm. Participants received 50 (n = 3), 75 (n = 7), 100 (n = 3) LSD, 50 µg followed by 75 µg LSD (n = 9) 1 week apart, or placebo followed by a 75 µg LSD (n = 10) 1 week apart. No serious adverse events were reported, This data indicates that LSD is safe and well-tolerated with mild adverse events reported.