Effects of Nicotine on Brain Activity as Measured by fMRI



Status:Archived
Conditions:Smoking Cessation, Psychiatric, Tobacco Consumers
Therapuetic Areas:Psychiatry / Psychology, Pulmonary / Respiratory Diseases
Healthy:No
Age Range:Any
Updated:7/1/2011
Start Date:August 2002

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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....


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.


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