Inclusion Criteria (AUD Group):
1. Be between the ages of 21 and 65
2. Meet current (i.e., past month) DSM-5 diagnostic criteria for moderate to severe AUD
3. Alcohol use disorder identification test (AUDIT) score \<20
4. Be non-treatment seeking for AUD
5. Report drinking more than 14 drinks per week if male (more than 7 drinks per week if female) in the 30 days prior to consent.
6. Must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile:
* Oral contraceptives
* Contraceptive sponge
* Patch
* Double barrier
* Intrauterine contraceptive device
* Etonogestrel implant
* Medroxyprogesterone acetate contraceptive injection
* Complete abstinence from sexual intercourse
* Hormonal vaginal contraceptive ring
Inclusion Criteria (Control Group):
1. Be between the ages of 21 and 65
2. No lifetime history (i.e., past year) DSM-5 diagnostic criteria for AUD
3. Alcohol use disorder identification test (AUDIT) score \<8
4. Report drinking at or below moderate drinking levels (≤7 drinks/week for females, ≤14 drinks/week for males) in the 30 days prior to consent.
5. Must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile:
* Oral contraceptives
* Contraceptive sponge
* Patch
* Double barrier
* Intrauterine contraceptive device
* Etonogestrel implant
* Medroxyprogesterone acetate contraceptive injection
* Complete abstinence from sexual intercourse
* Hormonal vaginal contraceptive ring
Exclusion Criteria (All Groups):
1. Have a current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
2. Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, major depressive disorder, or any psychotic disorder
3. Have current moderate to severe depression as indicated by a score of ≥ 21 on the Beck Depression Inventory - II (BDI-II)
4. Have current suicidal ideation or lifetime history of suicide attempt as reported onvthe Columbia-Suicide Severity Rating Scale (C-SSRS)
5. Have a positive urine screen for drugs other than cannabis;
6. Have clinically significant alcohol withdrawal symptoms as indicated by a score ≥ 8 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R)
7. Have an intense fear of needles or have had any adverse reactions to needle puncture
8. Be pregnant, nursing, or planning to become pregnant while taking part in the study
9. Have a body mass index (BMI) greater than 30
10. Have a medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes, autoimmune or inflammatory disease)
11. Have clinically significant abnormal EKG
12. Have \> Grade 2 laboratory abnormalities, based on FDA Guidance Document "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"
13. Have any other circumstances that, in the opinion of the investigators, compromises participant safety
To participate in the inflammatory challenge, participants must not show any of the following upon arrival to the inflammatory challenge study visit:
1. BrAC \> 0.000 g/dl
2. clinical withdrawal (CIWA-R) score ≥ 8
3. blood pressure ≤ 90/60 or ≥ 160/120
4. resting pulse ≤ 50 beats/minute or \> 100 beats/minute
5. temperature ≥ 99.5°F
6. recent (past 2 weeks) acute illness or vaccination
7. score of 10+ on Physical Sickness Symptoms Assessment
