Behavioral and Neurochemical Mechanisms Underlying Stress-Precipitated Drinking

The primary goal of this project is to build upon our promising pilot data and conduct the first human laboratory study evaluating effect of stress on the ability to resist drinking and subsequent alcohol consumption in individuals with alcohol use disorders versus social drinking controls. Importantly, we will measure HPA-axis reactivity and subjective reactivity (e.g., craving) as mechanisms underlying stress-precipitated drinking. Results will: 1) Determine whether individuals with alcohol use disorders versus social drinking controls are more reactive to stress-precipitated drinking outcomes; 2) Provide important evidence that targeting brain stress systems and stress reactivity is a viable medication development strategy for alcohol use disorders; 3) Identify potential mechanisms underlying the effect of stress on alcohol use outcomes; and 4) Provide the data necessary to expand this investigation to a Phase II clinical trial. Taken together, the innovative components of this proposal will guide development of treatments targeting the HPA-axis system for alcohol use disorders.

Inclusion Criteria:

1) Age 21-55

2) Able to read and write English

3) Capable of giving informed consent for the study

4) No history of psychotic disorder

Inclusion criteria for alcohol use disorders:

1) Meets DSM-5 criteria for current (past 6 months) moderate to severe alcohol use disorders

2) Drinking criteria: Males - Drinks > 21 drinks per week or 4 drinks per drinking day; Females -

Drinks > 14 drinks per week or 3 drinks per drinking day

3) 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)

Inclusion criteria for social drinkers (healthy controls):

1) Social drinking controls must report drinking 21 drinks or less per month for women and 35

drinks or less per month for men, and have at least 1 drink per month.

2) Does not meet criteria for DSM-5 AUD

3) Have no uncontrolled medical condition such as neurological, cardiovascular, endocrine,

renal, liver, or thyroid pathology

4) Have no history of a neurological or psychiatric disorder (e.g., DSM-5 Axis 1 diagnosis in 2

preceding years)

3) 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)

Exclusion Criteria:

1) A positive drug screen (except cannabis) at screening

2) Significant psychiatric history other than included disorders

3) Pregnancy/breastfeeding

4) Presence of acute or unstable medical or neurological illness that in the PI’s assessment puts

the subject at increased risk by participating in the study

5) Subjects with infectious, inflammatory, or immunocompromising conditions, including

cancers, HIV, hepatitis B or C

6) Subjects with disorders affecting the brain, including but not limited to multiple sclerosis,

stroke, tumors, intracranial bleeding, infection, abscess or seizures

7) BMI > 40

8) Any heart, renal or blood disease