Effects of Naltrexone on Nicotine Reinforcement
Condition: Tobacco Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Naltrexone; Placebo
Intervention description: All participants took naltrexone during one of the two 4-day study medication periods. Both 4-day study medication periods were randomized and counterbalanced between naltrexone and placebo; all study medication periods were separated by a 5-7 day washout period.
Dosing of the naltrexone was the same for all participants: Day 1: 12.5mg, Day 2: 25mg, Days 3 and 4: 50mg.; All participants took a placebo (sugar pill) during one of the two 4-day study medication periods. Both 4-day study medication periods were randomized and counterbalanced between naltrexone and placebo.
Placebo capsules matched the naltrexone in color, weight and inactive ingredients. The only difference the lack of active naltrexone in each capsule.
Intervention MeSH terms: Naltrexone
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: within-subjects, crossover, laboratory study; Naltrexone vs. Placebo

Summary:

      Despite preclinical evidence supporting the role of the endogenous opioid system in the
      reinforcing effects of nicotine, the efficacy of the opioid antagonist naltrexone (NTX) as a
      tobacco dependence treatment remains unresolved. Research is needed to identify those smokers
      for whom NTX will have the strongest beneficial effects on smoking behavior.

      The research bridges existing knowledge of genetic, pharmacologic, and behavioral responses
      to nicotine, and translates this knowledge to treatment for tobacco dependence. The immediate
      goal was to test whether genetic variation in the mu-opioid receptor gene predicts the
      effects of naltrexone (NTX) on nicotine reinforcement.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants must be greater than or equal to 18 years

          2. Based on the medical history, physical and laboratory examination, female subjects
             must:

               1. Agree in consent to practice effective contraception during study, be status
                  post-bilateral tubal litigation or be post-menopausal.

               2. Not be pregnant, nursing, or planning pregnancy

          3. Based upon self-report, subjects must smoke greater than or equal to 10 non-menthol
             cigarettes per day

          4. Because the OPRM1 variant is common (25-30%) in persons of European ancestry, but very
             rare in other ethnic groups (e.g., 2-9% of African Americans) it is not scientifically
             justified to include members of other ethnic groups. Therefore, only persons of
             European ancestry will be recruited.

          5. Following orientation by the research staff, subjects must sign written informed
             consent and HIPAA form.

        Exclusion Criteria:

          1. Current diagnosis of kidney disease or history of renal function impairment (unless
             they have recent kidney function tests (within last 3 months) and approval of their
             primary physician to participate in the study.)

          2. Women who are pregnant, planning a pregnancy, or lactating

          3. Current alcohol use > 25 standard drinks/week (this is because NTX is used to treat
             alcohol dependence, and effects of NTX on alcohol consumption in alcohol dependent
             subjects could have indirect effects on cigarette consumption).

          4. Current medical problems for which NTX is contraindicated including: active hepatitis
             (Liver Function Tests 3 times the Upper Limit of Normal).

          5. History of opiate dependence (prescription drug or illicit use).

          6. History of or current Diagnostic and Statistical Manual of Mental Disorders (Version
             IV) (DSM IV) substance use disorders (abuse or dependence involving alcohol, cocaine,
             stimulants, or benzodiazepines)

          7. Diagnosis of bulimia and/or anorexia nervosa in the last year

          8. Current or past use (with in past 12 months) of any medications containing NTX (e.g.,
             Revia, Trexan), allergy to NTX

          9. Concomitant medications (e.g., monoamine oxidase inhibitors or benzodiazepines within
             past 14 days, antipsychotics, antidepressants, theophylline, systemic steroids,
             over-the-counter stimulants and anorectics)