St. John's Wort for Tobacco Cessation
Condition: Smoking; Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Placebo; St. John's Wort-900 mg/day; St. John's Wort-1800mg/day
Intervention description: Placebo (inactive drug) given 3 times per day; St. John's Wort - 300 mg tables -3 times per day; St. John's Wort - 600 mg tables - 3 times per day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 118.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      After a steady decline for the last 50 years, the prevalence of tobacco use in the United
      States has reached a plateau of approximately 23%. Currently available treatments among
      adults are expensive and not efficacious for all tobacco users. New pharmacologic agents need
      to be developed and tested to achieve the Healthy People 2010 goal of less than a 12% adult
      tobacco use prevalence.

      Bupropion, an FDA approved agent for tobacco cessation, acts by inhibiting central
      synaptosomal reuptake of dopamine and norepinephrine. A widely used herbal antidepressant,
      St. John's Wort (SJW), shares a similar mechanism of action and is effective for treating
      mild to moderate depression. SJW is well tolerated, available over the counter, and is
      significantly less expensive than the established treatments for tobacco dependence.

      To date, no prospective clinical trial evaluating the efficacy of SJW for the treatment of
      tobacco use has been published. We propose to evaluate the efficacy of SJW for increasing
      tobacco abstinence and decreasing nicotine withdrawal symptoms in a randomized, double-blind,
      placebo-controlled, three-arm, parallel group, dose-ranging clinical trial. Participants
      (N=120) will be randomly assigned to one of the three groups and will receive a twelve-week
      course of SJW 900 mg per day, 1800 mg per day, or a matching placebo.

      This study is anticipated to provide the data needed to develop a larger randomized
      controlled clinical trial submitted through the R01 funding mechanism.
    

Eligibility criteria:

        A total of 120 subjects will be recruited in the study. Subjects will be eligible to
        participate if they:

          1. Are at least 18 years of age;

          2. Smoked more than10 cigarettes/day for the past one year;

          3. Willing to make a quit attempt;

          4. Able to participate fully in all aspects of the study; and

          5. Have been provided with, understand, and have signed the informed consent.

        Individuals will be excluded from study participation if they:

          1. Meet diagnostic criteria for current major depressive disorder or lifetime history of
             bipolar disorder or schizophrenia. Patients with mild or moderate depressive symptoms
             [Beck Depression Inventory, Second Edition &#8804; 28], but who do not meet current
             diagnostic criteria for major depressive disorder, will be included;

          2. Are currently (within past 30 days) using antipsychotics or antidepressants;

          3. Are currently (in previous 30 days) using any treatments for tobacco dependence (i.e.,
             behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or
             nortriptyline);

          4. Have used an investigational drug within the 30 days prior to enrolling in this study;

          5. Have ever used an herbal product for tobacco cessation;

          6. Have recent history (in the past 3 months) of alcohol abuse or dependence as assessed
             by the CAGE questionnaire and study investigators;

          7. Have a recent history of drug abuse as assessed by the Drug Abuse Screening Test 20
             (DAST-20) and physician interview;

          8. Are pregnant, lactating, or of child bearing potential, likely to become pregnant
             during the medication phase and not willing to use a reliable form of contraception.
             Reliable forms of contraception include barrier (diaphragm or condom with spermicidal
             jelly), injections, intrauterine device [IUD], surgical sterilization and abstinence;

          9. Have a history of any major cardiovascular events in the past 6 months including
             unstable angina, acute MI or coronary angioplasty;

         10. Have clinically significant acute or chronic progressive or unstable neurologic,
             hepatic, renal, cardiovascular, respiratory or metabolic disease;

         11. Are currently on medications interacting with St. John?s Wort including warfarin,
             antiretrovirals (particularly indinavir and nevirapine), cyclosporine and tacrolimus,
             digoxin, nifedipine and verapamil, theophylline, all serotonergic drugs (serotonin
             reuptake inhibitors, tricyclic antidepressants, tramadol, venlafaxine, tryptophan and
             buspirone), MAO inhibitors, oral contraceptives, anti-cancer agents including imatinib
             and irinotecan, migraine medications (sumatriptan and zolmitriptan), methadone,
             lithium, sibutramine, atorvastatin and simvastatin, midazolam, alprazolam,
             fexofenadine, omeprazole, and general anesthetics (fentanyl, propofol, and
             sevoflurane);

         12. Have another household member or relative participating in the study;

         13. Have a known allergy to St. John?s Wort;

         14. Have a history of photosensitivity;

         15. Are professional drivers or operators of heavy machinery; and

         16. Are scheduled for a planned surgical procedure within five days of taking SJW.