Neural Mechanisms Underlying Nicotine and Alcohol Combinations
Condition: Focus: Effects of Nicotine and Alcohol on Brain Circuits
Study type: Interventional

Summary: 
      Nicotine and alcohol are frequently used together and their combined use contributes to more
      than half a million deaths each year, with more alcoholics dying from smoking-related
      diseases than from alcohol-related diseases. Using a new multi-modal MRI approach combined
      with data fusion, the investigators propose to study how nicotine modulates alcohol-induced
      changes in the function of brain circuits. The investigators hypotheses are:

        -  functional connectivity (FC) in the reward network, containing components of the
           mesolimbic dopamine system, will be altered by alcohol, and additional increases in FC
           will be observed if nicotine is also present (e.g., additive effects).

        -  co-administration of nicotine will counteract the effects of alcohol on FC in multiple
           brain networks, including visual, sensorimotor and motor brain circuits, that may be
           associated with the impairing effects of alcohol
    

Detailed description: 
      Long-term Objectives: Our long-term objective is to bring together non-invasive quantitative
      functional magnetic resonance imaging (q-fMRI) with a newly developed cutting-edge analysis
      method to study changes in neuronal metabolism and cerebrovascular function that occurs
      during psychoactive drug use.

      Specific Aims: Our first specific aim is to validate the components of the q-fMRI
      acquisition, which requires several different kinds of fMRI scans (or multimodal
      measurements). The second aim then applies the q-MRI method to study the functional brain
      networks that define brain activity when a person is simply resting and not engaged in any
      activity. These networks each consist of a unique set of regions that spontaneously fluctuate
      together in order to be "tuned" for future task performance. The effects of nicotine and
      alcohol and their interaction on these resting state networks are the focus of the
      application of our new q-fMRI strategy. q-fMRI measurements require several different scans,
      including making measurements of perfusion and oxygen metabolism, and an integrated analysis
      of all of these different results will be much more informative than separate analyses of
      each measurement. However, the analysis method, the linked independent component analysis
      (linked ICA) approach is very new and has never been applied to q-fMRI measurements or any
      other measurements of psychoactive drug effects. Thus, the third aim is to apply this novel
      analysis method to data acquired under different drug conditions to identify patterns of
      related activity in our multimodal fMRI data.

      Research Design and Methods: A randomized within-subject study of 23 healthy subjects will be
      done as follows: fMRI scanning will begin four hours after pre-treatment with either nicotine
      or placebo patch (randomized). Alcohol will then be consumed by subjects while in the scanner
      and a second scanning session will be done of the combination of nicotine (placebo) + alcohol
      to assess changes in resting state functional connectivity due to alcohol and nicotine and
      their interactions.

      Significance: Linked ICA with q-fMRI measurements is an innovative strategy for studying
      brain function that could have a significant impact in the ability of fMRI to give an
      integrated picture of the spectrum of effects that drugs of abuse may have on brain function,
      and is thus ideally suited to the goals of the CEBRA mechanism. By applying this technique to
      study alcohol and nicotine co-use, we also will contribute greatly to the understanding of
      this significant health problem.
    

Intervention name(s): Nicotine + Alcohol; Placebo Nicotine + Alcohol; Nicotine + Placebo Alcohol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 14 mg nicotine patch applied in combination with vodka and orange juice alcoholic beverage (to reach blood alcohol level (BAL) = 0.08 based on subject weight, which is approximately 2-3 drinks for 400 mL volume); Placebo nicotine patch applied in combination with vodka and orange juice alcoholic beverage (to reach BAL = 0.08 based on subject weight, which is approximately 2-3 drinks for 400 mL volume); 14 mg nicotine patch applied in combination with 400 mL orange juice beverage with a trace of alcohol to create placebo alcohol mixture.
Other intervention name(s): Nicoderm CQ Clear; Absolute Vodka; Nicoderm CQ Clear; Absolute Vodka; Nicoderm CQ Clear; Absolute Vodka
Intervention MeSH terms: Ethanol; Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: alcohol; nicotine; addiction; functional MRI; functional connectivity; brain circuits