Galantamine Effects on Nicotine Responses in Smokers

In this double-blind, crossover study, the investigators are proposing to evaluate
galantamine's effects on the subjective nicotine effects and the severity of tobacco
withdrawal symptoms. Twenty four male and female smokers will first have two 4-day treatment
periods, in which subjects will be randomized to galantamine (8 mg/day) or placebo. These
treatment periods will be separated by a 3 to 14 day washout period. This range of washout
period, while minimizing carryover medication effects between treatments, will provide
flexibility for subjects to comply with study procedures. During study participation,
subjects will be instructed to continue to smoke as usual during the study except the 2.5
days of smoking abstinence before each test session. Starting at 10 p.m. on Day 1 of each
treatment period, subjects will refrain from smoking for approximately 2.5 days, until the
test session on Day 4. Subjects will have twice daily outpatient visits during the first 3
days and a test session on day 4. During the outpatient visits, study medication will be
administered and tobacco withdrawal symptoms and compliance with smoking abstinence will be
monitored. On Day 4 of each treatment phase subjects will have a test session, where they
will receive saline or 1.0 mg/70 kg of nicotine intravenously in a random, double-blind
manner. The sequence of nicotine treatments will be counterbalanced among subjects such that
equal number of subjects will receive saline first or nicotine first. Following each saline
and nicotine administration, physiological, subjective and cognitive measurements will be
obtained.

Currently 12 subjects completed this protocol. This study is in data analysis. (April 2011)

Inclusion criteria:

- female and male smokers, aged 18 to 55 years;

- history of smoking daily for the past 12 months, at least 15 cigarettes daily;

- CO level > 10ppm;

- for women: not pregnant as determined by pregnancy screening, nor breast feeding, and
using acceptable birth control methods.

Exclusion criteria:

- history of major medical illnesses including asthma or chronic obstructive lung
disease, history or current gastrointestinal ulcer, hepatic or renal impairment and
cardiac rhythm disturbances or other medical conditions that the study physician
deems contraindicated for the subject to be in the study;

- regular use of psychotropic medication (antidepressants, antipsychotics, or
anxiolytics) and/or recent psychiatric diagnosis and treatment for Axis I disorders
including major depression, bipolar affective disorder, schizophrenia and panic
disorder within the past year;

- current dependence on alcohol or on drugs or treatments for drug or alcohol addiction
;

- use of drugs that slow heart rate (eg, beta-blockers), which may increase the risk of
bradycardia and AV block, or NSAIDs, which may increase potential for developing
ulcers/active or occult gastrointestinal bleeding;

- known allergy to galantamine