Modeling Stress-precipitated Smoking Behavior for Medication Development

• number of cigarettes smoking during the ad-lib period [ Time Frame: during the laboratory sessions ] [ Designated as safety issue: No ]
• success rates in smoking cessation attempt [ Time Frame: during smoking cessation attempt ] [ Designated as safety issue: No ]
• gender differences in medication effects [ Time Frame: lab session and smoking cessation attempt ] [ Designated as safety issue: No ]

• number of cigarettes smoking during the ad-lib period [ Time Frame: during the laboratory sessions ] [ Designated as safety issue: No ]
• success rates in smoking cessation attempt [ Time Frame: during smoking cessation attempt ] [ Designated as safety issue: No ]

The purpose of this study is to examine whether guanfacine or carvedilol will attenuate the ability of stress to precipitate smoking lapse behavior in treatment seeking and non-treatment seeking daily smokers. Participants seeking treatment for smoking will participate in a smoking cessation attempt after the laboratory sessions. Also looking at gender differences.

• Drug: guanfacine
  3 mg/day, with 3-week lead-in medication period. The starting dose is 0.5 mg/day for days 1-3, followed by 1.5mg/day for days 4-7, followed by 2 mg/day for days 8-12, followed by 2.5 mg/day for days 13-15, followed by 3 mg/day from day 16 to remainder of study. 5-day taper at end of study.
  Other Name: Tenex
• Drug: placebo
  placebo
• Drug: Carvedilol
  50 mg/day titrated to stead state. The starting dose is 12.5 mg/day for day 1, followed by 25 mg/day for days 2-3, followed by 50 mg from days 4 to the end of the study.
  Other Name: Coreg

• Experimental: Guanfacine
  guanfacine 3mg/day
  Intervention: Drug: guanfacine
• Placebo Comparator: Placebo
  placebo control
  Intervention: Drug: placebo
• Experimental: Carvedilol
  Carvedilol 50 mg/day
  Intervention: Drug: Carvedilol

Inclusion Criteria:

• ages 18-60
• able to read and write in English
• smokers

Exclusion Criteria:

• any significant current medical conditions that would contraindicate smoking
• current DSM-IV abuse or dependence of other substances, other than nicotine (or caffeine) dependence
• positive test result at intake appointments on urine drug screens conducted for opiates, cocaine, or benzodiazepines
• women who are pregnant or nursing
• suicidal, homicidal or evidence of severe mental illness
• participants prescribed any psychotropic drug in the 30 days prior to study enrollment
• blood donation within the past 6 weeks
• participants who have engaged in a quit attempt in the past 3 months
• specific exclusions for administration of guanfacine/carvedilol not already specified include: Hypotensive individuals with sitting blood pressure below 90/50 mmHG; EKG evidence at baseline screening of any clinically significant conduction abnormalities, including a Bazlett's QTc >450 msec for men and QTc>470 msec for women; known intolerance for guanfacine

• National Institute on Drug Abuse (NIDA)
• Office of Research on Women's Health (ORWH)