A Dose-Ranging Study of 50 µg to 100 µg LSD in Healthy Volunteers

NCT05674669 | Completed Phase 1

• 2 other identifiers: CAS-50-37-3-022015-003151-21
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Assessment of Adverse Events by % frequency

  Assessment of Adverse Events by % frequency to assess the safety and tolerability of LSD

  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

  24 hours

• Cmax (pg/mL)drug

  Cmax (pg/mL): maximum drug plasma concentration

  24 hours

• Tmax (h)

  Tmax (h): time to reach maximum plasma concentration, T1/2 (h): time to reach half of maximum drug plasma concentration

  24 hours

Secondary Outcomes (4)

• Assess subjective drug effects using a VAS.

  12 hours

• Assess subjective drug effects on the 5D-ASC

  12 hours

• Assess ego dissolution by the EDI

  12 hours

• Assess the characteristics of altered states of consciousness assessed by the MEQ

  12 hours

Study Arms (5)

Group 1 N=3

EXPERIMENTAL

Single dose, follow-up visits at one day, one week, and one month after dose.

Drug: Lysergic Acid Diethylamide (LSD) 50µg

Group 2 N=7

EXPERIMENTAL

Single dose, follow-up visits at one day, one week, and one month after dose.

Drug: Lysergic Acid Diethylamide (LSD) 75µg

Group 3 N=3

EXPERIMENTAL

Single dose, follow-up visits at one day, one week, and one month after dose.

Drug: Lysergic Acid Diethylamide (LSD) 100µg

Group 4 N=10

EXPERIMENTAL

Randomized treatment with placebo followed by single dose, separated by 7 days. Follow-up visits at one day, one week, and one month after last dose.

Drug: Placebo/Lysergic Acid Diethylamide (LSD) 75µg

Group 5 N=9

EXPERIMENTAL

Randomized treatment with single dose followed by second dose, separated by 7 days. Follow-up visits at one day, one week, and one month after last dose.

Drug: Lysergic Acid Diethylamide (LSD) 50µg/75µg

Interventions

Lysergic Acid Diethylamide (LSD) 50µg DRUG

Group 1 N=3

Lysergic Acid Diethylamide (LSD) 75µg DRUG

Group 2 N=7

Lysergic Acid Diethylamide (LSD) 100µg DRUG

Group 3 N=3

Placebo/Lysergic Acid Diethylamide (LSD) 75µg DRUG

Group 4 N=10

Lysergic Acid Diethylamide (LSD) 50µg/75µg DRUG

Group 5 N=9

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female subject aged 21 to 65 years inclusive.
• For Part 1, subject has been previously exposed to LSD or any other classic psychedelic drug, including psilocybin, mescaline, and ayahuasca, on more than 3 occasions during their lifetime. For Part 2, Subject has not been previously exposed to LSD or any other classic psychedelic drug, including psilocybin, mescaline, and ayahuasca, during the past 7 years.
• Subject was able and willing to give written informed consent, adhere to the compliance terms during participation in the study, undergo the examinations and testing set forth in the clinical study protocol, and clearly and reliably communicate their subjective experiences to the investigator.
• Female participants of childbearing potential and male participants whose partner was of childbearing potential must have been willing to ensure that they or their partner used effective contraception during the study and for 3 months after the final study drug administration.

You may not qualify if:

• A. General Health
• Subject had a presence or clinically relevant history of any psychiatric, respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as judged by the investigator.
• Subject had a resting blood pressure exceeding 140 mmHg (systolic) or 90 mmHg (diastolic), averaged across 4 assessments taken at least 1 minute apart on the same day.
• Subject had a presence or relevant history of organic brain disorders (e.g., intracranial hypertension, aneurisms, impaired consciousness, lethargy, or brain tumour).
• Subject had a relevant history of atopy, hypersensitivity, skin allergies, or allergic reactions to drugs.
• Subject had a clinical laboratory test result outside the reference ranges of the testing laboratory and considered clinically significant by the investigator.
• Subject was positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency (HIV) virus I or II at screening.
• Subject was a current smoker (i.e., had smoked within 1 month prior to the screening visit).
• Subject had a medical history that would affect the subject's safety or the study endpoints.
• Subject had used prescription drugs which might potentially interact with the pharmacokinetics of LSD or therapy within 14 days of first dosing, unless agreed as not clinically relevant by the PI and the Medical Monitor.
• Subject had used over the counter (OTC) medication or therapy, including megadose vitamin therapy (but excluding routine vitamins) within 7 days of first dosing, unless agreed as not clinically relevant by the PI and the Medical Monitor.
• Subject had donated or received any blood or blood products within the previous 3 months prior to first dosing.
• Subject could not use a computer to complete simple tasks such as responding to an email.
• Subject had used any investigational drug or participated in any clinical trial within 3 months of their first dosing.
• Subject had a current sleep disorder.

Sponsors & Collaborators

• Eleusis Therapeutics: lead

Study Sites (1)

PAREXEL, Early Phase Clinical Unit

London, United Kingdom

Location

MeSH Terms

Interventions

Lysergic Acid Diethylamide

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Director of Research and Development

  Eleusis Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: January 6, 2023
• Study Start: October 20, 2015
• Primary Completion: July 26, 2016
• Study Completion: July 17, 2017
• Last Updated: January 6, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)