Effects of Nicotine on Brain Activity as Measured by fMRI
Condition: Nicotine Dependence; Drug Abuse
MeSH terms: Tobacco Use Disorder; Substance-Related Disorders
Study type: Observational

Summary: 
      Background:

      - Nicotine addiction is common among people who smoke tobacco, and the addictive properties
      of nicotine make smoking cessation difficult even for people who want to quit. Research has
      shown that smoking causes changes in the brain that lead to addiction and craving, but more
      research is needed to determine how different doses of nicotine and different intervals of
      receiving nicotine affect brain function. A greater understanding of nicotine's effect on the
      brain, as studied through functional magnetic resonance imaging (fMRI), may improve the
      effectiveness of smoking cessation therapies and treatments.

      Objectives:

      - To determine the effects of nicotine on brain function and chemistry in experienced
      cigarette smokers.

      Eligibility:

      - Current smokers (at least 20 cigarettes per day for at least 1 year) between 18 and 50
      years of age.

      Design:

        -  The study involves five separate research experiments. Most participants will be
           involved in only one experiment.

        -  The experiments will evaluate brain activity and function using fMRI. Participants will
           be trained in a series of tests on cognitive function before beginning the experimental
           part of the study.

        -  Experiment 1: Participants will have three fMRI scan sessions after receiving different
           dose levels of intravenous nicotine.

        -  Experiment 2: Participants will have four fMRI scan sessions after receiving two doses
           of nicotine separated by 1/4, 1/2, 3, and 24 hours.

        -  Experiment 3: Participants will have two sets of nicotine injections separated by 45
           minutes, with each injection series containing five rapid injections of small amounts of
           nicotine (to mimic five puffs on a cigarette).

        -  Experiment 4: Participants will have three fMRI sessions after receiving a single
           injection of nicotine at three different rates (over 15, 60, or 120 seconds). In
           addition there will be three more sessions involving a nicotine patch and a nicotine
           injection as well as a placebo session.

        -  Experiment 5: Participants will have three fMRI sessions that will involve looking at
           different kinds of pictures related to or not related to smoking after receiving a
           single injection of nicotine.

        -  Participants will also provide blood samples for further study....
    

Detailed description: 
      Objective:

      The overall goal of this protocol is to employ fMRI to define nicotine's neural
      pharmacokinetic and pharmacodynamic properties and neurochemical sites and mechanisms of
      action in experienced smokers and to correlate these with monoamine and nicotinic receptor
      genotypes as well as to determine behavioral correlates of nicotine during various conditions
      of delivery and regress behavioral correlates of nicotine administration against
      neuroanatomical sites of activation across subjects.

      Study Population:

      The study population will consist of adult (18-50 y.o.) non-treatment seeking smokers.
      Subjects must smoke at least 20 cigarettes per day for at least 1 year. They cannot be
      dependent on any drug or alcohol except nicotine and caffeine. In addition, they must be
      appropriate candidates for fMRI scanning.

      Design:

      The study is divided into 5 separate arms with a maximum of two arms being conducted at one
      time. The experimental arms explore the effect of intravenous nicotine delivery with respect
      to the following parameters: dosage, interval of delivery, rate of delivery and emotional
      processing. Specifically the arms are as follows: Experiment 1: 3 fMRI scan sessions each
      administering either 0.25, 0.75 and 1.5 mg IV nicotine; Experiment 2: 4 fMRI scan sessions
      administering two doses of 1.25 mg nicotine separated by 0.25, 0.75, 3 and 24 hours;
      Experiment 3: two injection series separated by 45 minutes, each injection series containing
      5 rapid injections of 0.25 mg each, much like 5 puffs on a cigarette; Experiment 4: 3 fMRI
      sessions administering a single injection of 1.5 mg nicotine at 3 different rates- over 15,
      60 or 120 seconds; and Experiment 5: 3 fMRI session administering 1.5 mg nicotine followed by
      exposure to either neutral, negative, or positive affect pictures. Since experimental arms
      are conducted in series, rather than in parallel, there are very few subjects common to more
      than one experimental arm.

      Outcome Measures:

      The relevant outcome measures in this study are the behavioral and physiological effects and
      the patterns of brain regions activated (or suppressed) following the intravenous
      administration of nicotine across varying doses, intervals, rates and the effect on these
      parameters of emotional processing in the context of nicotine of stimuli with different
      affective valence.
    

Keywords: Intravenous; Rate of Delivery; Dose Responses; Variable Intervals; Multiple Rapid Injections