Effect of Galantamine on Short-term Abstinence

Nicotine dependence is a major public health problem and currently available treatments are
ineffective for the majority of smokers. Thus, there is an urgent need to develop and test
new medications to aid in smoking cessation. Recent evidence from a genetic study of
prospective smoking cessation conducted at the CIRNA suggested smoking cessation may be
influenced by variationin acetylcholine levels. The proposed proof-of-concept study is a
randomized, double-blind, placebo-controlled, parallel arm pilot study of the effects of the
acetylcholinesterase inhibitor, galantamine (vs. placebo), on short-term abstinence among 24
treatment-seeking smokers. The primary outcome is the number of days abstinence a 7 day quit
attempt. Secondary outcomes include: smoking rate during the run-up and monitored abstinence
phase, medication adherence, side effects, cognitio, and smoking urges and other withdrawal
symptons. The pilot data generated will be used to support an NIH grant application by a new
investigatot to evaluate whether acetylcholinesterase inhibitors could be effective smoking
cessation medications.

Inclusion Criteria:

- Must be between the ages of 18 and 60

- Must report smoking at least 10 cigarettes per day for the past 6 months

- Must be able to provide informed consent

- Must express interest in quitting smoking in the next 2 to 6 months.

- Using a scale from 0 to 100, they must rate their confidence that they will make a
quit attempt in the next 6 months a 50 or higher.

Exclusion Criteria

- Smoking Behavior:

1. Daily use of chewing tobacco, snuff, and/or snus.

2. Current enrollment in a smoking cessation program, or use of other smoking
cessation medications in the last month or plans to do either in the next month.

3. Provide a carbon monoxide (CO) breath sample reading less than 10 parts per
million (ppm) at Intake.

- Alcohol/Drugs:

1. History of substance abuse in the past 6 months and/or currently receiving
treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or
stimulants) as determined by self-report during the phone screen and/or through
the MINI during the Intake. Subjects reporting a history of substance abuse must
be in remission at least 6 months or greater.

2. Current alcohol consumption that exceeds 25 standard drinks/week over the past 6
months.

3. Providing a breath alcohol concentration (BrAC) reading of greater than or equal
to 0.01 at Intake, Baseline, or Testing Days.

4. A positive urine drug screen for cocaine, amphetamines, methamphetamines,
benzodiazepines, PCP, methadone, barbiturates, and opiates at the Intake,
Baseline, or Testing days.

- Medical:

1. Women who are pregnant, planning a pregnancy in the next 3 months, or lactating;
all female subjects shall undergo a urine pregnancy test at the Intake and must
agree in writing to use an approved method of contraception. Following
enrollment, pregnancy tests will be conducted at the Baseline and Testing days
for all female subjects of child-bearing potential.

2. Diagnosis of Alzheimer's Disease or dementia.

3. Current treatment of cancer or diagnosed with cancer (except basal cell
carcinoma) in the past 6 months.

4. Liver/kidney failure, peptic ulcer disease, benign prostate hypertrophy.

5. Asthma or chronic obstructive pulmonary disease (COPD).

6. History (last 6 months) of abnormal heart rhythms, tachycardia and/or
cardiovascular disease (stroke, angina, heart attack). These conditions will be
evaluated on a case by case basis by the Study Physician/Health Care Provider.

7. Serious or unstable disease within the past 6 months, as determined by the Study
Physician/Health Care Provider.

8. Any impairment (physical and/or neurological) including visual or other
impairment preventing cognitive task performance.

9. Uncontrolled high blood pressure (SBP>160 or DBP>100).

10. Hearing impairment, significant hearing loss (more than 20% in either ear),
cochlear implants, or bi-lateral hearing aids.

11. History of brain injury.

12. History of epilepsy or a seizure disorder.

13. Color Blindness.

14. Low or borderline intellectual functioning - determined by receiving a score of
less than 90 on the Shipley Institute of Living Scale (SILS) which correlates
with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated IQ Test
(administered at Intake).

- Psychiatric Exclusion (as determined by self-report on phone screen and/or through
MINI during Intake):

1. Current diagnosis of major depression. Persons with a history of major
depression, in remission for 6 months or longer, are eligible, provided they are
not excluded based on medications (below).

2. Suicide risk score on MINI greater than 0.

3. History or current diagnosis of schizophrenia, psychosis, and/or bipolar
disorder.

4. Current or past hypomanic/manic episode.

5. Current or history of a diagnosis of Attention-Deficit/Hyperactivity Disorder
(ADHD).

Medication:

1. Current use, recent discontinuation (within the last month) of any form of smoking
cessation medications (i.e., Zyban, Wellbutrin, Wellbutrin SR, Chantix, nicotine
replacement therapy);

2. Current use or recent discontinuation (within the last 60 days) of:

1. Anti-anxiety or panic disorder medications.

2. Anti-psychotic medications.

3. Mood-stabilizers (e.g., Lithium, Lamictal/lamotrigine, Neurontin/gabapentin,
Topamax/topiramate, valproic acid, Tegretol/carbamazepine).

4. Anti-depressants (e.g., Wellbutrin, MAOIs, SSRIs, tricyclic antidepressants).

5. Prescription stimulants (e.g., Provigil, Ritalin, Adderall).

6. Systemic Steroids (e.g., Prednisone).

7. Alzheimer's disease medications (e.g., Acetylcholinesterase inhibitors (ACIs),
Aricept/donepezil, Exelon/rivastigmine, Tacrine, or memantine).

8. Parkinson's disease medications(e.g., Cogentin/benztropine).

9. Irritable bowel syndrome medication (e.g., Dicylomine/Bentyl).

10. Heart medications (e.g., quinidine or Procardia/nifedipine).

11. Peptic ulcer disease medication (e.g, Zantac/ranitidine).

12. Muscle relaxants (e.g., Soma/carisoprodol, Anectine/succinylcholine).

13. Anti-fungal medication (e.g., Nizoral/ketoconazole).

14. Anti-seizure medications (e.g., Ativan, Banzel, Carbatrol, Dilantin, Lamictal,
Gabitril, Lyrica, Neurontin, Tegretol, Topomax).

15. COPD medication (e.g., Atrovent/Ipratropium Bromide). .

16. Urinary retention medications (e.g., Duvoid/bethanechol, Proscar/finasteride,
Avodart/dutasteride, Dibenzyline/phenoxybenzamine, Regitine/phentolamine).

17. Eye medication (e.g., Atropine).

3. Daily use of:

1. Opiate-containing medications for chronic pain (Duragesic/fentanyl patches,
Percocet, Oxycontin).

2. Medication for asthma (albuterol, Serevent, Combivent, Advair, Flovent,
Azmacort, Symbicort).

4. Known allergy to study medication.

- Current, anticipated, or pending enrollment in another research program over the
next 2-3 months that could potentially affect subject safety and/or the study
data/design as determined by the Principal Investigator and/or Study Physician.

- Not planning to live in the area for the next two months.

- No children under the age of 18, pregnant women, fetuses, neonates, or prisoners
are included in this research study.

- Any medical condition, illness, disorder, or concomitant medication that could
compromise participant safety or treatment, as determined by the Principal
Investigator and/or Study Physician.

- Inability to provide informed consent or complete any of the study tasks as
determined by the Principal Investigator.

- Completion of neurocognitive assessments and/or use of study medication(s) at
the CIRNA in the past 6-months that could influence performance on study tasks
as determined by the Principal Investigator.

- Not able to effectively communicate in English (reading, writing, speaking).