A Dose-Ranging Study of 50 µg to 100 µg LSD in Healthy Volunteers
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Lysergic Acid Diethylamide (LSD) 50µg; Lysergic Acid Diethylamide (LSD) 75µg; Lysergic Acid Diethylamide (LSD) 100µg; Placebo/Lysergic Acid Diethylamide (LSD) 75µg; Lysergic Acid Diethylamide (LSD) 50µg/75µg
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Lysergic Acid Diethylamide
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: In Part 1, each subject was allocated to open label treatment with a single dose of 50 µg, 75 µg, or 100 µg LSD. Part 1 was conducted in hallucinogen non-naive participants. In Part 2, each subject was randomized to double blind treatment and received 50 µg LSD followed by 75 µg LSD (experimental non-crossover group), or placebo followed by 75 µg LSD (placebo-controlled crossover group), with dosing separated by at least 7 days. Part 2 was conducted in hallucinogen naive participants.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other