Baclofen Effects on Smoking Urge and Withdrawal

OBJECTIVES: The long-term objective of this research program is to improve treatments for
tobacco smokers by investigating the effects of medications on self-reported and
psychophysiological responses to smoking cues and on behavioral-economic measures of smoking
reinforcement during a period of tobacco deprivation. The specific objectives of the present
application are to investigate the dose-response effects of baclofen (a gamma-aminobutyric
acid B agonist), 1) on urge, and withdrawal, and 2) on the reinforcement value of smoking as
measured by choices for puffs on cigarettes versus an alternative reinforcer among current
smokers after 4 hours of smoking deprivation. RESEARCH PLAN: The study will use a randomized
placebo-controlled between-subjects design with 64 smokers to investigate the effects of
placebo and two doses (20 or 40 mg/day) of baclofen on urge to smoke and withdrawal and on
choices for smoking versus money after 4 hours of deprivation. METHODS: Participants will be
healthy people who smoke at least 10 cigarettes per day and who are motivated for future
smoking cessation. On Day 0, a baseline session will occur after 4 hours of smoking
deprivation and on Day 10 of medication the same assessments will be repeated after the
final medication dose has been stabilized for at least 3 days and after 4 hours of
supervised smoking deprivation has occurred. Medication differences in urge and withdrawal
and in the reinforcement value of smoking cigarettes will be investigated. Dependent
measures of urge and withdrawal will be by self-report. The dependent measure of
reinforcement value is the ratio of choices for cigarette puffs versus money during a
subsequent 2-1/2 hr period. The choice procedure will clarify the relative reinforcement
value of smoking while controlling for non-specific decreases in general activity level
resulting from sedation. Nicotine self-administration during the medication period will be
quantified using saliva cotinine, as a secondary effect. CLINICAL RELEVANCE: More effective
interventions for tobacco use could result in less suffering and mortality and in
considerable savings in health care costs associated with cardiovascular disease, pulmonary
disorders, and cancer.

Inclusion Criteria:

- Smoke at least 10 cigarettes per day for at least 6 months and considering quitting
smoking in the next 6 months-

Exclusion Criteria:

- Planning to attempt smoking cessation within the next 4 months

- Weight less than 110 lbs. or above 220 lbs.

- Use of tobacco products other than cigarettes in the previous month.

- History of: Kidney disease, uncontrolled conditions (e.g., cardiac disease, pulmonary
disease, diabetes, hypertension) Neurological disease (including stroke, mini-stroke,
brain injury, Alzheimers Disease, encephalitis, meningitis, seizure
disorder),Phenylketonuria Schizophrenia, Schizoaffective Disorder, Paranoid Disorder,
or Schizotypal Disorder.

- Current alcohol and/or drug use disorder as indicated by a screening questionnaire,
past treatment for alcohol or substance use problems unless in remission(clean and
sober for past year or more) or intention to seek treatment in the next 6 months for
alcohol or substance use problems.

- For women: Pregnancy, nursing, not using a reliable form of birth control.

- Allergy to baclofen, Lioresal, or Kemstro.

- Taking the following medications: antidepressants(excluding selective serotonin
reuptake inhibitors), bupropion, phenothiazines, antihistamines, sedative/hypnotics,
benzodiazepines, alpha blockers, beta blockers.

- Lives with someone enrolled in the study.