The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder

This is an open label feasibility trial to learn whether the combination of donepezil and cognitive remediation therapy (Donepezil + CRT) may improve neurocognitive functioning and decreasing alcohol use in Veterans with alcohol use disorder who have mild cognitive impairment (AUD-MCI). The study will determine the acceptability and adherence to treatment and preliminary evidence for efficacy. The study will recruit 15 newly recovering Veterans individuals with AUD-MCI for a 13-week, open-label, single-arm pilot study with sobriety and cognitive assessments at baseline and at 13-week follow-up.

Donepezil is FDA approved for treatment of dementia and recent animal studies have suggested that it may reduce craving in rat models of alcohol use disorder. Investigators' previous studies of cognitive remediation therapy (CRT) with work therapy have shown efficacy with newly recovering Veterans with AUD compared with work therapy alone. The current study combines Donepezil and CRT in an open-label trial to learn whether the combination of Donepezil + CRT may improve neurocognitive functioning and decrease alcohol use in Veterans with alcohol use disorder who have mild cognitive impairment (AUD-MCI). The study will determine the acceptability and adherence to treatment and provide preliminary evidence for efficacy. The study will recruit 15 newly recovering Veterans individuals with AUD-MCI for a 13-week, open-label, single-arm pilot study with sobriety and cognitive assessments at baseline and at 13-week follow-up. Primary outcome variables will be a Clinical Global Index of AUD recovery and a Global Cognitive Composite of MCI related neurocognitive assessment.

Eligibility Criteria:
Inclusion Criteria:

* Males and females 21-80 years of age
* Fluency in English and a 6th grade or higher reading level
* Meets DSM-V criteria for a current Alcohol Use Disorder
* Referred for the study within 30 days of detoxification or last substance use according to medical records
* Willingness to attend follow-up assessments at 13 weeks
* Willingness to submit to Breathalyzer screenings and Urine Toxicology screenings.
* Meets MCI criteria with greater than 1.5 SD below pre-morbid IQ estimate or 1.5 SD below standard norms on at least 1 key neurocognitive MCI related variable (Learning and Memory, Delayed Recall, Executive Function, Working Memory).

Exclusion Criteria:

* Lifetime diagnosis of a psychotic disorder, not induced by drug use.
* Current prescribed treatment of opioids or benzodiazepines, which may affect new learning Involvement in a legal case that may lead to incarceration during study period
* Residential plans that would interfere with participation
* Medical illness that may significantly compromise cognition (e.g. Parkinson's, Alzheimer's, Huntington's Chorea, Moderate or greater TBI).
* An uncorrected sensory impairment (hearing or sight) that would seriously interfere with cognitive training.
* Pre-morbid IQ estimate below 70.
* Unstable housing or lack of commitment to staying within a geographic area that would make follow-up possible.
* Unwillingness to provide contact information of someone who can help study staff contact the participant in the event that study staff are unable to maintain contact directly.
* Allergy to Donepezil.
* Unstable cardiovascular disease or unstable medical condition-clinically determined by a physician.
* Imminent suicidal or homicidal risk.
* Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential.