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LSD Treatment for Persons With Alcohol Use Disorder

Phase 2
Not yet recruiting
Conditions
Alcohol Use Disorder (AUD)
Interventions
Drug: Active placebo
Registration Number
NCT05474989
Lead Sponsor
Felix Mueller
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 the short-term after withdrawal.

Lysergic acid diethylamide (LSD) was investigated in numerous clinical trials during the 1950s and 1960s. 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. However, these trials are limited by several factors, including the use of diagnostic standards that are no longer not up to date, single, high-dose treatment regimes, missing biological assessment for alcohol use, and no consequent assessment of blinding.

Therefore, the present study aims to evaluate the safety and efficacy of LSD for the treatment of AUD and addresses the shortcomings of previous studies. The trial has a double-blind, active placebo-controlled, randomized, parallel design and will be conducted in specialized treatment centers for addictive disorders in Switzerland. The study will include 126 patients after withdrawal treatment and will primarily assess the efficacy of LSD for the treatment of AUD. Patients will be treated using a 1:1 allocation. Each arm will last 20 weeks and will comprise nine study visits without drug administration and two study days involving LSD or active placebo administration. 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, the study will assess neurobiological mechanisms of action and several other measures.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
126
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active placeboActive placeboSubjects in the control arm will receive 10 µg LSD at the first session and 10 µg LSD at the second session.
VerumLSDSubjects in the treatment arm will receive 150 μg LSD (first session) and 150 or 250 μg LSD (second session).
Primary Outcome Measures
NameTimeMethod
Percent heavy drinking daysPeriod of three months after the second intervention

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 Outcome Measures
NameTimeMethod
CravingThree months after the second intervention

Craving assessed with Obsessive Compulsive Drinking Scale

DepressionThree months after the second intervention

Hamilton Depression Rating Scale

BlindingIn the evening after administration 1 (week 4) and administration 2 (week 8), respectively

Blinding will be assessed directly after each session by asking patients and therapists to guess the group assignment ("high dose", "low dose", "don't know") and to provide their degree of certainty (using a visual analogue scale) of their guess.

The volume of the striatum measured with MRITwo weeks before first administration, two and 12 weeks after second administration

Changes in the volume of the striatum

White matter microstructure measured with MRITwo weeks before first administration, two and 12 weeks after second administration

Changes in white matter microstructure in the cingulum bundle and the PFC-striatal connection pathway

Days to first drinking dayThree months after the second intervention

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

AnxietyThree months after the second intervention

Beck Anxiety Inventory

Cortical thickness measured with MRITwo weeks before first administration, two and 12 weeks after second administration

Changes in the cortical thickness of ACC, PCC, and PFC

Days to first heavy drinking dayThree months after the second intervention

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

PhosphatidylethanolScreening, day of first intervention, day of second intervention, three months after the second intervention

Phosphatidylethanol (PEth) in blood

Drinks per drinking dayThree months after the second intervention

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

General healthThree months after the second intervention

General health assessed with General Health Questionnaire

Percent days abstinentThree months after the second intervention

Percent days abstinent after first and second administration assessed with TLFB

Adverse consequences of alcohol useThree months after the second intervention

Adverse consequences of alcohol use assessed with Short Inventory of Problems

Ethyl glucuronideScreening and three months after the second intervention

Ethyl glucuronide (EtG) in hair

Safety: Adverse eventsWeek 0 to week 20

Adverse events will be documented at each visit and each session.

Trial Locations

Locations (2)

University Hospital of Psychiatry, University of Bern

🇨🇭

Bern, Switzerland

University Hospital of Psychiatry, University of Basel

🇨🇭

Basel, Switzerland

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