LSD Treatment for Persons With Alcohol Use Disorder

Alcohol Use Disorder (AUD) Clinical Trial

— LYSTA  

Official title:

LSD Treatment for Persons With Alcohol Use Disorder: A Multicenter, Double-blind, Randomized, Active-placebo Controlled Phase II Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05474989
• Other study ID #: 2022-00121
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2024
• Est. completion date: May 1, 2028

Study information

• Verified date: October 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Felix Müller, PD Dr. med.
• Phone: +41 (0)61 325 5111
• Email: felix.mueller[@]upk.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 126
• Est. completion date: May 1, 2028
• Est. primary completion date: May 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

Key inclusion criteria:

• age = 25 years
• moderate to severe AUD
• completion of a qualified detoxification for AUD within 30 days prior to screening
• a minimum of 4 heavy drinking days within the last 30 days before detoxification
• intention to stop or decrease drinking

Key exclusion criteria:

• significant alcohol withdrawal symptoms at screening
• participating or starting in any formal treatment for AUD until completion of visit 9
• cognitive impairment
• borderline personality disorder
• current post-traumatic stress disorder
• current suicidality or history of a serious suicide attempt
• significant prodromal symptoms
• history of a diagnosis of a psychotic or bipolar disorder in subjects or first-degree relatives
• pregnancy or breast-feeding
• lack of safe contraception are exclusion criterion for women only

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder (AUD)
• Alcoholism

Intervention

Drug:
• LSD
Moderate to high dose LSD
• Active placebo
Low dose LSD

Locations

Country	Name	City	State
Switzerland	University Hospital of Psychiatry, University of Basel	Basel
Switzerland	University Hospital of Psychiatry, University of Bern	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Felix Mueller	University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent heavy drinking days	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	Period of three months after the second intervention
Secondary	Cortical thickness measured with MRI	Changes in the cortical thickness of ACC, PCC, and PFC	Two weeks before first administration, two and 12 weeks after second administration
Secondary	The volume of the striatum measured with MRI	Changes in the volume of the striatum	Two weeks before first administration, two and 12 weeks after second administration
Secondary	White matter microstructure measured with MRI	Changes in white matter microstructure in the cingulum bundle and the PFC-striatal connection pathway	Two weeks before first administration, two and 12 weeks after second administration
Secondary	Days to first heavy drinking day	Days to first heavy drinking day after first and second administration assessed with TLFB	Three months after the second intervention
Secondary	Days to first drinking day	Days to first drinking day assessed after first and second administration assessed with TLFB	Three months after the second intervention
Secondary	Percent days abstinent	Percent days abstinent after first and second administration assessed with TLFB	Three months after the second intervention
Secondary	Drinks per drinking day	Drinks per drinking day after first and second administration assessed with TLF	Three months after the second intervention
Secondary	Adverse consequences of alcohol use	Adverse consequences of alcohol use assessed with Short Inventory of Problems	Three months after the second intervention
Secondary	Craving	Craving assessed with Obsessive Compulsive Drinking Scale	Three months after the second intervention
Secondary	Ethyl glucuronide	Ethyl glucuronide (EtG) in hair	Screening and three months after the second intervention
Secondary	Phosphatidylethanol	Phosphatidylethanol (PEth) in blood	Screening, day of first intervention, day of second intervention, three months after the second intervention
Secondary	General health	General health assessed with General Health Questionnaire	Three months after the second intervention
Secondary	Depression	Hamilton Depression Rating Scale	Three months after the second intervention
Secondary	Anxiety	Beck Anxiety Inventory	Three months after the second intervention
Secondary	Blinding	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.	In the evening after administration 1 (week 4) and administration 2 (week 8), respectively
Secondary	Safety: Adverse events	Adverse events will be documented at each visit and each session.	Week 0 to week 20