Investigating the balance of opioid receptors in alcohol use disorder

Investigating the Mu:Kappa Opioid Receptor Imbalance in Alcohol Use Disorder

This study is testing how the levels of certain brain receptors are different in people with alcohol use disorder compared to healthy individuals to see how these differences affect cravings, mood, and withdrawal during early recovery.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05957159 on ClinicalTrials.gov

What this trial studies

This study uses positron emission tomography (PET) imaging to measure Mu-Opioid receptors (MOR) and Kappa-Opioid receptors (KOR) in individuals with alcohol use disorder (AUD). It aims to compare receptor availability in participants with AUD during early abstinence to healthy controls, and to explore how these receptor levels relate to clinical outcomes such as craving, mood, and withdrawal. Participants will either undergo a medically supervised detoxification program or engage in outpatient abstinence with daily meetings. The study will involve 50 individuals with AUD and 50 matched healthy controls, with assessments conducted over a period of approximately six days.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with alcohol use disorder who are willing to abstain from alcohol and engage in a quit attempt.

Not a fit: Patients with no current or past diagnosis of alcohol use disorder or significant substance use disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and treatment strategies for individuals with alcohol use disorder.

How similar studies have performed: Other studies have explored opioid receptor dynamics in addiction, but this specific approach using multimodal PET imaging in AUD is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Participants with AUD will have a current diagnosis of AUD according to DSM-5 criteria (i.e., SCID-5 ascertained diagnosis, confirmed by the Principal Investigators);
* Participants with AUD will meet the following drinking criteria: males will drink \> 14 drinks per week and exceed 4 drinks per day at least twice per week; females will drink \> 7 drinks per week and exceed 3 drinks per day at least twice per week. They must meet drinking criteria during a consecutive 30-day period within the 90 days prior to intake;
* Participants with AUD will indicate willingness to abstain from alcohol and engage in a quit attempt;
* Healthy subjects will have no current or past diagnosis of AUD or other significant substance use disorder. They will drink less than 5 alcoholic drinks per week with no heavy drinking days (i.e., \>4 drinks/day for men; \>3 drinks/day for women) in the last 30 days;
* Able to read and write English and to provide voluntary, written informed consent;
* Agree to have blood drawn for genotyping of the OPRM1 which has been shown to impact the \[11C\]CFN outcome measure, BPND50.

Exclusion Criteria:

* Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology that would impact the integrity of the data (note that elevated liver enzymes for individuals with AUD will not be exclusionary);
* Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder;
* Current significant psychiatric disorder including severe substance use disorder (other than alcohol or tobacco use disorders\*), and past or current psychotic symptoms;
* Regular use in the past 6 months of any prescription, psychoactive or herbal medications (e.g., antidepressants, antipsychotics, anxiolytics) that would impact the integrity of the data (e.g., naltrexone); No subject will be asked to stop taking medication to participate in the study;
* Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or her partner is surgically sterile or she is postmenopausal (hormone contraceptives \[oral, implant, injection, patch, or ring\], contraceptive sponge, double barrier \[diaphragm or condom plus spermicide\], or IUD;
* Contraindications to MRI such as claustrophobia or metal in their body;
* Subjects whose participation would cause them to exceed yearly radiation limits for research subjects

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Kelly Cosgrove, PhD — Yale University
• Study coordinator: Marc Grasso

Conditions Alcohol Use Disorder; Alcohol; Alcohol cessation