Translational Neuropsychopharmacology Research of Nicotine Addiction
Condition: Nicotine Dependence, Cigarettes
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will examine the effects of combining Varenicline (VRN) and N-acetylcysteine (NAC)
      on neural circuitry function and treating nicotine addiction. Healthy adult nicotine
      dependent cigarette smokers interested in quitting (n=110) will be randomized to one of four
      PBO-controlled conditions for 4 weeks: 1) VRN+NAC, 2) VRN+PBO, 3) NAC+PBO or 4) PBO+PBO.
      Following 1 week of medication, participants will be contingently reinforced for 3 days of
      smoking abstinence and be scanned using functional magnetic resonance imaging (fMRI)
      techniques, while nicotine deprived during a resting state and a cue-reactivity (CR) task.
      Participants will be followed over the next 3 weeks of treatment and clinical variables will
      be assessed.
    

Detailed description: 
      Cigarette (henceforth nicotine) addiction is a chronic, relapsing brain disorder and remains
      the leading preventable cause of death and disability in the US, costing nearly $200 billion
      each year. Although ~20% of adults in the USA currently smoke, the majority want to quit. In
      spite of the breadth of research focused on improving health outcomes and reducing the
      societal burden caused by nicotine addiction, the majority of smokers who attempt to quit
      will relapse. Nicotine withdrawal-related disturbances in executive function, negative affect
      and reward processes compel a smoker to self-administer nicotine-each in turn representing
      the loss of control to remain abstinent and risk factors for relapse. Thus, identifying the
      effects of nicotine addiction on mechanisms of self-regulation, and the value of novel
      medications for remediating dysregulated behavior are both needed in order to enhance
      interventions for treating nicotine addiction. The preliminary data, along with the extant
      literature, suggest that the maintenance of nicotine addiction is subserved by dysregulated
      neural function in limbic-striatal and corticostriatal neural circuitry. While VRN may be
      effective in treating limbic-striatal circuitry that is associated with promoting abstinence
      and reducing acute withdrawal; NAC may be effective in treating corticostriatal circuitry
      function that is associated with relapse vulnerability. Thus, the current proposal seeks to
      investigate two medications (VRN & NAC), with potentially complementary effects on the two
      different brain circuits- limbic-striatal (VRN) and corticostriatal (NAC) circuitry-and that
      may therapeutically target two different phases in the recovery of nicotine addiction-the
      promotion of abstinence (VRN) and relapse prevention (NAC). The placebo (PBO)-controlled
      design in this proposal will allow the team to identify and translate between the
      neurobiological substrates and the neurocognitive underpinnings of the effects of VRN+NAC on
      smoking behavior in humans-thus, advancing the understanding of the pathophysiology of
      nicotine addiction.
    

Intervention name(s): Varenicline (VRN); N-Acetylcysteine (NAC); Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): VRN will be provided at the standard recommended dose (0.5 mg daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily thereafter for the remaining 21 days of active treatment.; NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment; Matched placebo
Intervention MeSH terms: Acetylcysteine; Varenicline; N-monoacetylcystine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Health Services Research