Alcohol Use Disorder (AUD)
Conditions
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.
Interventions
DRUGLSD
Moderate to high dose LSD
DRUGActive placebo
Low dose LSD
Sponsors
University of Bern
Felix Mueller
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent heavy drinking days | Period 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
| Measure | Time frame | Description |
|---|---|---|
| The volume of the striatum measured with MRI | Two weeks before first administration, two and 12 weeks after second administration | Changes in the volume of the striatum |
| White matter microstructure measured with MRI | Two 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 heavy drinking day | Three months after the second intervention | Days to first heavy drinking day after first and second administration assessed with TLFB |
| Days to first drinking day | Three months after the second intervention | Days to first drinking day assessed after first and second administration assessed with TLFB |
| Percent days abstinent | Three months after the second intervention | Percent days abstinent after first and second administration assessed with TLFB |
| Drinks per drinking day | Three months after the second intervention | Drinks per drinking day after first and second administration assessed with TLF |
| Adverse consequences of alcohol use | Three months after the second intervention | Adverse consequences of alcohol use assessed with Short Inventory of Problems |
| Cortical thickness measured with MRI | Two weeks before first administration, two and 12 weeks after second administration | Changes in the cortical thickness of ACC, PCC, and PFC |
| Ethyl glucuronide | Screening and three months after the second intervention | Ethyl glucuronide (EtG) in hair |
| Phosphatidylethanol | Screening, day of first intervention, day of second intervention, three months after the second intervention | Phosphatidylethanol (PEth) in blood |
| General health | Three months after the second intervention | General health assessed with General Health Questionnaire |
| Depression | Three months after the second intervention | Hamilton Depression Rating Scale |
| Anxiety | Three months after the second intervention | Beck Anxiety Inventory |
| Blinding | In 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. |
| Safety: Adverse events | Week 0 to week 20 | Adverse events will be documented at each visit and each session. |
| Craving | Three months after the second intervention | Craving assessed with Obsessive Compulsive Drinking Scale |
Countries
Switzerland
Contacts
Primary ContactFelix Müller, PD Dr. med.
Outcome results
None listed