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.
This study with low-dose LSD comprised 2 substudies in different populations of healthy subjects: Part 1: an open-label dose-escalation study in hallucinogen non-naïve subjects. Part 2: a double blind, placebo controlled, randomised, crossover study in hallucinogen naïve subjects. Part 1: Open-label, dose escalation study This part was performed in a population of healthy subjects with significant prior experience with hallucinogens. There was a screening period of up to 28 days. Following provision of informed consent and completion of all screening assessments, eligible subjects were assigned to the open-label dose-escalation group. Following completion of baseline assessments, each subject received a single dose of LSD: 50, 75, or 100 µg. This dose range was selected for assessment based on extensive historical and clinical LSD research. Subjects knew they would receive the experimental drug but were blinded to the dose level received. Subjects were followed up on the day after dosing and at 1 week and 1 month after dosing. During screening, baseline, treatment, and follow-up, subjects underwent a series of assessments. Included amongst these assessments were cognitive tasks that were administered at baseline before administration of LSD and subsequently during the study. The open-label study subjects also provided samples for PK analysis. Part 2: Double-blind, placebo controlled, randomised, crossover study This part commenced following evaluation of the results from Part 1. It was performed in a population of healthy subjects with no prior experience with hallucinogens during the last 7 years. There was a screening period of up to 28 days. Following provision of informed consent and completion of all screening assessments, eligible subjects were assigned to 1 of 8 cohorts and then randomly assigned to 1 of 2 treatment groups. Cognitive assessments were administered at baseline before administration of the first dose and subsequently during the study. Following completion of baseline assessments, subjects entered a 2 week treatment period: the experimental non-crossover group received 2 sequential escalating single doses of LSD administered at levels determined in Part 1 (50 µg followed by 75 µg, or placebo followed by 75 µg), with dosing separated by at least 7 days; the placebo controlled crossover group received placebo followed at least 7 days later by a single dose of 75 µg LSD, as determined in Part 1. Subjects were followed up on the day after each dosing, 1 week after the second dose, and at 1 month after the last dose of study treatment. During screening, baseline, treatment and follow-up days, subjects underwent a series of assessments.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
32
PAREXEL, Early Phase Clinical Unit
London, United Kingdom
Assessment of Adverse Events by % frequency
Assessment of Adverse Events by % frequency to assess the safety and tolerability of LSD
Time frame: 1 year
AUC 0-24h ( pg/mL*h) over time
AUC 0-24h ( pg/mL\*h): area under the plasma concentration-time curve profiles from time zero to the 24 hour sample determined using the linear trapezoidal rule
Time frame: 24 hours
Cmax (pg/mL)drug
Cmax (pg/mL): maximum drug plasma concentration
Time frame: 24 hours
Tmax (h)
Tmax (h): time to reach maximum plasma concentration, T1/2 (h): time to reach half of maximum drug plasma concentration
Time frame: 24 hours
Assess subjective drug effects using a VAS.
Assessed by the Visual Analog Scale (VAS). Items assess acute subjective drug effects (e.g. intensity, liking) Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects
Time frame: 12 hours
Assess subjective drug effects on the 5D-ASC
5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The scale ranges from no, not more than usual (on the left) to yes, very much more than usual (on the right). Items retrospectively assess subjective drug effects. Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects associated with a different state of consciousness
Time frame: 12 hours
Assess ego dissolution by the EDI
The EDI is an eight-item questionnaire designed to measure ego dissolution. Each item is scored on a 5-point Likert-type scale, and the inventory includes a single factor. Higher scores indicate greater subjective effects associated with a different state of consciousness
Time frame: 12 hours
Assess the characteristics of altered states of consciousness assessed by the MEQ
The MEQ is a 30-item self-report questionnaire developed for detecting and characterizing mystical experiences induced by classic psychedelics. Each item is scored on a 5-point Likert-type scale, and derived scores for the MEQ include four scales: mystical, positive mood, transcendence of time and space, and ineffability. In addition, a response of more than or equal to 60% of each and every scale would classify an experience as a 'complete mystical experience'. Higher scores indicate greater subjective effects associated with a different state of consciousness.
Time frame: 12 hours
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