Alcohol Related Impairment and Reinforcement: Pre to Post Roux en Y Gastric Bypass Surgery

The three major objectives of this NIH sponsored application are: 1) to characterize the
severity of cognitive impairment and driving performance changes following alcohol
consumption in a group of patients who have undergone Roux-en-Y Gastric Bypass (RYGB)
bariatric surgery and 2) to investigate differential reinforcing properties of alcohol in
patients before and after they undergo RYGB. Both of these objectives stem from observations
from the investigators work and previous empirical studies suggesting that the
pharmacokinetics (PK) of alcohol are substantially altered following bariatric surgery. This
may lead to alterations in the time-course and severity of alcohol-related cognitive and
driving impairment, as well as alter the reinforcing effects of drinking alcohol.
Particularly relevant to these objectives, PK data have shown higher peak alcohol
concentrations and a shorter time to achieve them in bariatric surgery patients. Therefore
the third objective of this application is to better characterize the PK profile of alcohol
following RYGB. Finally, investigators will explore whether changes in impairment,
reinforcement, and PKs are moderated by gender, age, smoking, and alcohol use.

In this study investigators propose to prospectively investigate approximately 50-60 RYGB
patients. Participants will be assessed at baseline (pre-surgery) and one year after surgery
(to approximate their weight nadir) in an acute alcohol dosing laboratory paradigm.

Inclusion Criteria:

1. Male or female (approximately 50% each)

2. 21 - 65 years of age

3. In evaluation for Roux-en-Y gastric bypass surgery

4. Able to tolerate alcohol dose

5. Cognitive ability to complete study protocol as assessed at screening

6. Medically stable

Exclusion Criteria:

1. History of or current alcohol use disorder (as assessed at screening)

2. Psychotic or bipolar spectrum disorder (as assessed at screening)

3. Current suicidality (as assessed at screening)

4. Concomitant medication known to significantly interact with alcohol

5. Concomitant medication known to significantly impact driving simulator performance

6. Pregnancy or intending to become pregnant prior to the end of the their participation
in the study or breastfeeding

7. Positive urine drug screen

8. Unable to tolerate blood draws

9. Significant risk for developing motion sickness while using the driving simulator

10. Unable to speak English

11. Other factor that would increase participant risk in the protocol in the judgement of
the investigators or physician.

12. Participated in an investigational drug study within the past 30 days

13. Is or has an immediate family member that is employeed by the Neuropsychiatric
Research Institute

14. Has a pacemaker

15. Insulin dependent diabetes mellitus

16. Smoking defined as regular use of nicotine in the past 6 months

17. A presurgery weight of > 400lbs at screening appointment or as reported on telephone
screen

18. Unable to provide a blood sample at the screening appointment or is assessed to have
poor vein quality for IV placement as determined by the research clinical personnel.

19. Laboratory abnormalities defined as a hepatic panel greater than three times the
upper limit of normal, or fasting glucose of < 60 or >120 mg/dl, or positive
pregnancy test.