Exenatide For Reducing the Reinforcing Effects of Cocaine

Inclusion Criteria:

1. English-speaking

2. Male or female ≥ 18 and ≤ 65 years of age

3. Willing and able to provide written informed consent and participate in all requiredstudy activities

4. Self-reported recent use of smoked or IV COC verified by a COC positive urine (≥ 150ng/mL)

5. Report using COC for ≥ 10 years and using ≥ 2 grams of COC/week

6. Have vital signs as follows, resting pulse between 50 and 95 bpm, blood pressure (BP) between 90-150 mmHg systolic and 45-95 mmHg diastolic.

7. Have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exception, pancreatic tests (lipase and amylase) must bewithin normal limits

8. Have a medical history, physical examination, electrocardiogram (ECG), drug-usehistory, and the Mini-International Neuropsychiatric Interview (M.I.N.I.)demonstrating no clinically significant contraindications for study participation,in the judgment of a Study Physician and the Principal Investigator.

9. Agree (if the subject is female and of child-bearing potential) to use at least oneof the following methods of birth control from time of the first administration ofthe study drug to at least 7 days post the last dose of study drug, unless thepartner is surgically sterile (underwent vasectomy),

10. oral contraceptives,

11. contraceptive sponge,

12. patch,

13. double barrier (diaphragm/spermicidal or condom/spermicidal),

14. intrauterine contraceptive system,

15. etonogestrel implant,

16. medroxyprogesterone acetate contraceptive injection,

17. complete abstinence from sexual intercourse, and/or

18. hormonal vaginal contraceptive ring

19. Women of child-bearing potential must provide negative urine pregnancy tests priorto randomization, and at study visits as indicated in the Research Strategy

20. No contraindications/allergies to COC or exenatide

21. Cardiovascular and subjective responses to COC within acceptable

Exclusion Criteria:

1. Clinically significant medical conditions .

2. Meet diagnostic criteria for substance-use disorders other than for CUD that in theopinion of the study physician would comprise the well-being of the participant.

3. Seeking treatment for a substance use disorder.

4. Any laboratory test deemed clinically significant by the study physician.

5. Type 1 or type 2 Diabetes Mellitus (HbA1C level of ≥6.5%)

6. Previous medically adverse reaction to the study medications (Bydureon) or COC.

7. Medication use that might interact with COC or exenatide, or otherwise compromisesafety.

8. Personal or family history of medullary thyroid carcinoma or multiple endocrineneoplasia syndrome type 2.

9. Severe cardiovascular disease (history of myocardial infarction, life-threateningarrhythmia, or worsening angina pectoris).

10. Severe gastrointestinal disease (i.e., severe gastroparesis).

11. Previous history of pancreatitis or risk of pancreatitis.

12. Creatinine clearance <45 or end stage renal disease (ESRD).

13. Contraindications to treatment with exenatide (e.g., personal of family history ofmedullary thyroid carcinoma or multiple endocrine neoplasia syndrome type-2; historyof pancreatitis or risk of pancreatitis).

14. Participation in a clinical trial within 30 days of admission.

15. Positive urine pregnancy test or females trying to conceive, donated ova, arepregnant, or are lactating or breast feeding at screening or throughout study.

16. Positive urine screen for drugs-of-abuse, other than COC or marijuana, or breathalcohol test. Note, if positive for opioids or oxycodone but recent opioid use foracute pain is reported by the subject, then the subject can be included at thediscretion of the Primary Investigator and/or Study Physician.

17. Have a history of suicidal ideation.

18. Have any illness or condition which in the opinion of the Principal Investigatorand/or the Study Physician would preclude safe and/or successful completion of thestudy.