Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine

The aim of this study is to test whether the attention-enhancing effects of low-dose nicotine can be enhanced by the drug galantamine, FDA-approved for the treatment of Alzheimer's disease. This proof-of-principle study is performed in healthy non-smokers and involves two single exposures to a nicotine patch (7 mg/24 hrs) and two single exposures to galantamine (4 mg). The dose of galantamine is substantially lower than the clinical dose range of 16-24 mg/day. The hypothesis is that performance-enhancing effects of nicotine are greater in the presence of this low dose of galantamine.

Healthy non-smokers will be screened for study eligibility and receive training on three different attention tasks. Over four test session, participants will then perform these tasks after receiving (1) a placebo patch and a placebo capsule, (2) a nicotine patch (7 mg/24 hrs) and a placebo capsule, (3) a placebo patch and a galantamine capsule, and (4) a nicotine patch and a galantamine capsule. The four test session are performed on separate days and take approximately 7 hours each. During the first 5 hours, the participant may read or watch TV while nicotine and/or galantamine are being absorbed. During the last two hours, the participant will perform the attention tasks on a computer. The investigators hypothesize that performance-enhancing effects of nicotine, which were documented in previous research, will be larger in the presence than in the absence of galantamine. This proof-of-concept would have implications for the development of drugs for the treatment of conditions such as Alzheimer's disease or schizophrenia.

Eligibility Criteria:
Inclusion Criteria:

* Aged 21 to 55 years.
* No exposure to any nicotine-containing product in the last year.
* Smoked no more that 40 cigarettes, cigars or cigarillos in lifetime.
* Normal or corrected to normal vision (at least 20/80).
* Body weight 110-220 lbs.

Exclusion Criteria:

* Pregnant or breast-feeding.
* Drug or alcohol abuse or dependence currently or in the last 2 years.
* DSM Axis I mood, anxiety or psychotic disorder.
* Cardiovascular or cerebrovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities (Wolf-Parkinson-White syndrome, Complete left bundle branch block, PR interval \<120 ms or \>200 ms, Prolonged QT interval (corrected) \>500 ms, Cardiac arrhythmias as defined by PACs \>3 per min or PVCs \>1 per min).
* Uncontrolled hypertension (resting systolic BP above 140 or diastolic above 90 mm Hg).
* Hypotension (resting systolic BP below 90 or diastolic below 60).
* Significant kidney or liver impairment.
* Moderate to severe asthma.
* Obstructive pulmonary disease.
* Type I or II diabetes.
* Use of any centrally active medications; any peripherally acting cholinergic medications; cimetidine; ketoconazole; erythromycin; quinidine, or chronic nonsteroidal anti-inflammatory drugs.
* History of or current neurological illnesses, such as stroke, seizure disorders, neurodegenerative diseases, or organic brain syndrome.
* Learning disability, mental retardation, or any other condition that impedes cognition.
* Heart rate \<55 bpm.
* Current or history of gastric ulcer disease.
* Any surgeries requiring full anesthesia scheduled within 2 weeks of any of the study test sessions.
* Anemia.
* Inability to perform the Rapid Visual Information Processing Task.