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.
- 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.
- 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
- 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
- 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
- Inability to perform the Rapid Visual Information Processing Task.