Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction
Condition: Smoking
MeSH terms: Behavior, Addictive
Study type: Interventional
Phase: Phase 1

Summary: 
      In the present study the investigators will measure the effects of nicotine and non-nicotine
      factors on brain function during cognitive processes that are differentially sensitive to
      these factors. One process-continuous working memory (CWM)-is implemented via a network of
      frontal and parietal brain regions and is highly dopamine dependent. Smoking cessation
      results in significant deficits in CWM which can persist for weeks and are reversed by
      resumption of nicotine administration in the form of smoking or nicotine replacement.
      Additionally, CWM deficits are observed during smoking of denic cigarettes. Brain function
      during CWM is modulated by smoking abstinence and subsequent nicotine administration and
      activity in the dlPFC is implicated in these effects. Collectively, these data suggest that
      CWM is highly sensitive to the nicotine, but not non-nicotine components of smoking. Brain
      function during CWM is altered by smoking abstinence and nicotine, but the effect of smoking,
      in the absence of nicotine, has not been evaluated.

      Another process-cue-reactivity (CR)-results from the repeated pairing of otherwise neutral
      stimuli with nicotine administration. Acute smoking cessation has not been shown to have
      strong effects on CR in the form of cue-provoked craving, nor has nicotine replacement been
      shown to have robust effects on CR. Likewise, the direct effects of smoking abstinence on
      brain CR have been small; though craving has been shown to modulate relations between
      abstinence and CR. Moreover, recent data from our lab suggest larger 'doses' of abstinence (~
      24 hrs) may amplify brain responses to cues. The effect of smoking in the absence of
      nicotine, on CR has not, to our knowledge, been evaluated. Collectively, these data suggest
      that CR in the form of cue-induced craving is not highly sensitive to the effects of
      short-term smoking abstinence or nicotine. Brain CR is modulated by abstinence-induced
      craving and longer-term abstinence, but it is unclear whether abstinence from nicotine or
      non-nicotine components is responsible for these effects.

      In the present study, we propose to evaluate the effects of non-nicotine and nicotine factors
      on CWM and CR using functional magnetic resonance imaging. This method allows for the
      non-invasive assessment of brain function. We will also examine the role of genes in
      moderating and mediating the effects of nicotine and non-nicotine factors on cognitive
      function
    

Detailed description: 
      Overview. In a fully factorial design, thirty-six (n=36) adult smokers will undergo fMRI
      scanning at least 24 hours after each of the following conditions: 1) Nicotine Patch + Denic
      Smoking, 2) Placebo Patch + Denic Smoking, 3) Nicotine Patch + No Smoking, and 4) Placebo
      Patch+ No Smoking. During scanning, participants will complete a laboratory based measure of
      continuous working memory (n-back)-a measure of continuous working memory-and the
      cue-reactivity task (CR)-a measure of responses to smoking cues. Broadly, we hypothesize 1)
      abstinence from nicotine, regardless of smoking, will disrupt CWM performance and brain
      function, 2) abstinence from nicotine and denics will potentiate brain CR but differentially
      contribute to this effect and 3) that individual differences in smoking behavior and
      motivation will predict the effects of nicotine and non-nicotine factors on brain function.
    

Intervention name(s): Quit smoking; Nicotine patch; Placebo Patch
Intervention type(s): Behavioral; Drug; Drug
Intervention description(s): Subjects will quit smoking for 2 fMRIs, each abstinence lasting 2 days; Subjects will wear a 21mg patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.; Subjects will wear a placebo patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Health Services Research
Keywords: smoking; nicotine; Effects of nicotine and non-nicotine factors on continuous working memory.; Effects of nicotine and non-nicotine factors on cue reactivity.; Use of nicotine patches, placebo patches, and denicotinized cigarettes.; memory