LSD Treatment for Persons With Alcohol Use Disorder

LSD

Brief Summary

Alcohol use causes more overall harm than any other drug and is the seventh leading risk factor for both deaths and disability-adjusted life years. Alcohol use disorders (AUD) are among the most common and undertreated mental disorders in developed countries. Pharmacological and psychotherapeutic treatments only show limited efficacy and around 60% of the patients relapse in short-term after withdrawal. Lysergic acid diethylamide (LSD) was extensively investigated in the 1950s and 1960s and became one of the best-studied psychoactive substances with several thousands of early scientific reports. Specifically, the use of LSD in the treatment of AUD was investigated extensively. A pooled analysis of six historical clinical trials demonstrated, that a single dose of LSD significantly reduced alcohol use at three and six months after LSD administration and the improvements surpassed treatment with established psychopharmacological interventions. However, these historical studies do not meet today's methodological standards which limits the validity of these findings. Well-designed studies are needed to further investigate this promising treatment approach. Therefore, the present study aims to evaluate safety and efficacy of LSD for the treatment of AUD. The trial has a double-blind, active placebo-controlled, randomized, parallel design and will be conducted in three specialized treatment centers for addictive disorders in Switzerland. The study will include 128 patients after withdrawal treatment and will primarily assess the efficacy of LSD for relapse prevention after standard detoxification. Patients will be treated using a 1:1 allocation. In the first session, patients in the treatment group will receive a dose of 150 µg LSD, followed by another 150 µg or 250 µg LSD in the second session, which will take place approximately 4 weeks after the first session. The primary outcome is the mean of percent heavy drinking days after administration of two doses of LSD at 3 months' follow-up. Additionally, other alcohol associated parameters and associated common comorbidities as well as potential predictors and mediators for treatment response will be assessed.

Intervention / Treatment

  • LSD (DRUG)
    Moderate to high dose LSD
  • Active placebo (DRUG)
    Low dose LSD

Condition or Disease

  • Alcohol Use Disorder (AUD)

Phase

  • Phase 2

    • Study Design

    Study type: INTERVENTIONAL
    Status: Not yet recruiting
    Study results: No Results Available
    Enrollment: 128 (ESTIMATED)
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    TRIPLE:
    • Participant
    • Care Provider
    • Investigator

    Clinical Trial Dates

    Start date: Jan 01, 2023 ESTIMATED
    Primary Completion: Jan 01, 2025 ESTIMATED
    Completion Date: Jan 01, 2025 ESTIMATED
    Study First Posted: Jul 26, 2022 ACTUAL
    Last Updated: Jul 24, 2022

    Sponsors / Collaborators

    Lead Sponsor: N/A
    Responsible Party: N/A

    Participant Groups

    • Subjects in the treatment arm will receive 150 μg LSD (first session) and 150 or 250 μg LSD (second session).

    • Subjects in the control arm will receive 10 µg LSD at the first session and 10 µg LSD at the second session.

    Eligibility Criteria

    Sex: All
    Minimum Age: 25
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion criteria:

    * Age ≥ 25 years
    * Participants must meet the DSM-V criteria for a moderate to severe alcohol use disorder and want to stop or decrease their drinking
    * Participants must have underwent an alcohol detoxification within the 30 days prior to screening
    * Participants must have been abstinent since withdrawal treatment
    * Participants must have had at least 20% heavy drinking days (HDD) in the 90 days prior to their alcohol detoxification.
    * Patients must be willing to discontinue medications (e.g. most antidepressants and antipsychotics) in cases where drug related interactions are possible (the washout phase will be at least 5 times the particular drug's half-life \[typically 3-7

    Exclusion criteria:

    * Moderate to severe cognitive impairment
    * Past or present diagnosis of a DSM-V psychotic or bipolar disorder in subjects or first-degree relatives
    * Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to LSD with high risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g. borderline personality disorder)
    * Suicide risk or very likely to require psychiatric hospitalization during the course of the study

    Primary Outcomes

    • The primary outcome is the mean of percent heavy drinking days after administration of two doses of LSD assessed with the alcohol timeline follow-back (TLFB) questionnaire compared between treatment groups

    Secondary Outcomes

    • Percent heavy drinking days after the first administration assessed with TLFB

    • Days to first heavy drinking day after first and second administration assessed with TLFB

    • Days to first drinking day assessed after first and second administration assessed with TLFB

    • Percent days abstinent after first and second administration assessed with TLFB

    • Drinks per drinking day after first and second administration assessed with TLF

    • Craving assessed with Obsessive Compulsive Drinking Scale

    • Carbohydrate-deficient transferrin (CDT) in blood

    • General health assessed with General Health Questionnaire

    • Adverse consequences of alcohol use assessed with Short Inventory of Problems

    • Impulsivity assessed with the Barratt impulsiveness Scale

    • Depression assessed with Inventory of Depressive Symptomatology - self rated

    • Anxiety assessed with Spielberger state-trait anxiety inventory

    • Persisting effects of LSD administration assessed with Persisting Effects Questionnaire

    More Details

    NCT Number: NCT05474989
    Other IDs: 2022-00121
    Study URL: https://clinicaltrials.gov/study/NCT05474989
    Last updated: Sep 29, 2023