Ketamine and Motivational Enhancement Therapy for the Treatment of Tobacco Use Disorder

Inclusion Criteria:

1. 21 to 65 years old.

2. Able to provide informed consent.

3. Be a daily cigarette smoker with multiple unsuccessful previous quit attempts, andreport a continued desire to quit smoking.

4. Agree to abstain from smoking for the ketamine session from 1 hour before ketamineadministration

5. Agree to refrain from using any psychoactive drugs, including alcoholic beverages,within 24 hours of ketamine administration. Exceptions include caffeine andnicotine.

6. Subjects taking other psychotropic medications must be maintained on a stable dosefor at least four weeks before study initiation.

7. Be healthy as determined by screening for medical problems via a personal interview,a medical questionnaire, a physical examination, an electrocardiogram (ECG) toverify normal QTc intervals.

8. Subjects with normal blood pressure not on antihypertensive medications ormedication controlled hypertension as defined baseline visit systolic blood pressure (SBP) <140 mmHg or a diastolic blood pressure (DBP) <90 mmHg.

Exclusion Criteria:

1. Women who are pregnant (positive pregnancy test) or nursing, or are not practicingan effective means of birth control which can include oral, implant, intrauterinedevice, or patch contraceptive methods as well as barrier contraceptive methods,history of surgery such as hysterectomy or tubal ligation, or abstinence

2. Subjects who meet DSM-5 criteria for current or history of psychotic spectrumdisorders or current depression or bipolar disorder based on clinical interview.

3. Subjects meeting DSM-5 criteria for current substance use disorder other thantobacco use disorder.

4. Subjects with hypertension as defined by a baseline visit systolic blood pressure (SBP) >140 mmHg or a diastolic blood pressure (DBP) >90 mmHg.

5. A history of allergic or other adverse reaction to ketamine (or its excipients).

6. Clinically significant physical exam findings or self-reported medical conditionsfor which a transient increase in blood pressure could be significantly detrimental (e.g. glaucoma, aneurysmal disease, cardiovascular disease, or end-stage renaldisease).

7. Cardiovascular conditions: uncontrolled hypertension, angina, a clinicallysignificant ECG abnormality (e.g., atrial fibrillation), TIA in the last 6 months,stroke, peripheral or pulmonary vascular disease

8. Subjects who live greater than 20 miles from the study site and cannot arrange theirown transportation will be excluded from the study.

9. Subjects with clinically significant kidney or liver impairment.

10. Have any current neurological illnesses including, but not limited to, seizuredisorders, frequent migraines or on prophylaxis, multiple sclerosis, movementdisorders, history of significant head trauma, or CNS tumor.

11. Morbidly obese (BMI >40), or severely underweight as determined by medicalexamination.