For this protocol, the investigators plan to collect data to evaluate apremilast (60mg/day) vs placebo in adults with Alcohol Use Disorders (AUD).

This human laboratory study is a Phase 2 double-blind, placebo-controlled, parallel group design which will compare apremilast (60mg/day) to placebo in non-treatment seeking adults meeting criteria for DSM 5 alcohol use disorders (n=80, 40 per cell, 50% females).

Eligibility screening consists of an intake session and a physical exam. Subjects meeting eligibility criteria will be assigned to apremilast (60mg/day) or placebo. Titration to steady state medication levels occur over 6 days (Day 1-6). Subjects will then complete three laboratory sessions (Days 7-24). During each laboratory session, personalized imagery (within-subject factor, either stress or stimulation or neutral, order counterbalanced) will precede a 2-hour alcohol self-administration period. Participants will remain on study medication for a 28-day period, during which naturalistic drinking will be evaluated.

No taper medication is needed. Following the discontinuation of medication (Day 30), participants will be assessed for an additional 1-month period.

Adverse events are evaluated at each study appointment and will be tabulated.

Inclusion Criteria:

1. Age 21-65.
2. Able to read and write English.
3. Meets DSM-5 criteria for current (past 6 months) AUD.
4. Drinking criteria: males - drinks > 14 drinks per week and exceeds 4 drinks per day at least twice per week; females - drinks > 7 drinks per week and exceeds 3 drinks per day at least twice per week. They must meet drinking criteria during a consecutive 30-day period prior to baseline.
5. Laboratory sessions will be scheduled such that subjects will not have major responsibilities on the following day which might limit drinking during the self-administration session (e.g., job interview, exam).
6. Able to take oral medications and willing to adhere to medication regimen.
7. Provision of signed and dated informed consent form
8. Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

1. Subjects with any significant current medical conditions (neurological, cardiovascular, endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions, including HIV.
2. Current DSM-5 substance use disorder (other than AUD or tobacco use disorder).
3. A positive test result at intake appointment on urine drug screens conducted for illicit drugs.
4. Past 30-day use of psychoactive drugs may be included at the discretion of the study MD as long as the concurrent treatment does not compromise the study integrity by virtue of its type, duration, or intensity.
5. 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).
6. Suicidal, homicidal, or evidence of current (past 6 months) mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders.
7. Only one member per household can participate in the study.
8. Specific exclusions for administration of apremilast not already specified include: known hypersensitivity to apremilast; cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin).
9. Drugs that may influence study outcomes (e.g., disulfiram, naltrexone, acamprosate, anticonvulsants).
10. Subjects likely to exhibit clinically significant alcohol withdrawal during the study. We will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal, or b) have a score of > 8 on the Clinical Institute Withdrawal Assessment scale at intake appointments.
11. Subjects who have taken any investigational drug within 4 weeks immediately preceding admission to the study period.
12. Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current application.
13. Individuals who are currently in treatment for drinking or who have attempted to quit drinking within the past 3 months in order to exclude participants seeking treatment.
14. Individuals with a history of serious withdrawal, and individuals who have repeatedly undergone alcohol detoxification.