Last updated on September 2018

Nicotine Withdrawal Symptoms and Smoking Relapse


Brief description of study

Background
  • Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Many people say that they continue smoking to help relieve these symptoms, often within the first week after trying to quit. Researchers want to study what is happening in the brain to cause these symptoms, which may help identify new ways to successfully quit smoking.
    Objectives
  • To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.
    Eligibility
  • Individuals between 18 and 55 years of age who smoke at least 10 cigarettes per day. Participants must be able to stop smoking for 36 hours on two occasions.
    Design
  • This study will involve three visits to the National Institute on Drug Abuse.
  • Participants will be screened with a medical history and physical exam. Blood and urine samples will be collected, as well as breath samples to test for recent alcohol use. Participants will also fill out questionnaires and learn about the tests at the next two visits.
  • Before each imaging visit, participants will stop smoking for 36 hours. Before one visit, participants will wear a nicotine skin patch. Before the other visit, participants will wear a placebo (dummy) patch with no nicotine. Participants will not be told which type of patch they are wearing. Participants will measure the level of carbon monoxide in their breath during both of these nonsmoking periods. They will also complete questionnaires about mood and cigarette cravings.
  • Participants will have two study visits with imaging studies to measure brain activity. Each imaging visit will last about 9 to 10 hours. The visit will involve two separate 1.5- to 2-hour scan sessions (a morning scan and an afternoon scan). These scan sessions will involve tests of concentration, memory, and reaction time. Other tests and questionnaires will also be completed outside of the scanner before and after the sessions.

Detailed Study Description

Objective

The primary objective of the current protocol is to gain a greater understanding of the neurobiological mechanisms underlying acute nicotine withdrawal and contributing to the maintenance of, or return to smoking behavior among nicotine-dependent individuals, in the service of developing future smoking cessation treatments. The Nicotine Withdrawal Syndrome is a major cause of failed quit attempts in smokers, and targeting this time period for intervention may help improve smoking cessation outcomes.

Study Population

We will recruit treatment seeking and non-treatment seeking smokers, as well as matched non-smoker control participants.

Design

There are 3 arms included in this protocol, each of which aims to understand the neurobiology of the Nicotine Withdrawal Syndrome during the initial quit period, with the broader goal of increasing quit success rate in the future.

Main Study: To understand (1) the acute neurobiological effects of nicotine withdrawal on treatment-seeking and non-treatment seeking smokers, (2) the long term neurobiological outcomes of varenicline treatment and smoking cessation counseling at 1, 6, and 12 months. We will recruit 85 treatment seeking and 35 non-treatment seeking smokers for a within (nicotine deprivation), between (treatment-seeking status) subjects randomized, double blind, placebo controlled study.

Motivational Interviewing Arm: (1) To increase motivation and preparation for smoking cessation treatment among individuals who express an interest in quitting smoking but are not currently ready to enter treatment, in the service of increasing quit success rate and (2) to understand the neurobiological basis of motivation to quit smoking, and the interaction between motivation to quit and mechanisms that underlie acute nicotine withdrawal. We will recruit 300 current smokers interested in quitting smoking, but not yet ready to set a quit date.

Transcranial Direct Current Stimulation (tDCS) Arm: To understand the acute effect of tDCS on 3 large-scale brain networks dysregulated in nicotine addiction and withdrawal, the Default Mode Network, the Executive Control Network, and the Salience Network. We will enroll 60 non-treatment seeking smokers, with the expectation of 35 completers; and enroll 55 non-smoking controls, with the expectation of 45 completers, for a double blind, sham controlled, randomized crossover study. Smokers will be studied in nicotine abstinence and nicotine sated conditions, as in the Main Study design.

Outcome measures

Primary outcome measures:

  1. Change in BOLD signal and FC related to task parameters, between drug (or tDCS) condition.
  2. Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making, cue reactivity and working memory (e.g., reaction time, error rate, hit rate, reward bias).
  3. Self-reported craving, withdrawal symptoms and mood/affect
  4. Smoking abstinence as determined by self-reported tobacco use, urine cotinine, and breath CO.

Secondary outcome measures:

  1. MRS for glutamate concentration.
  2. Plasma ACTH and cortisol.
  3. Resting state CBF from ASL.
  4. ERP and EEG measures.
  5. Ratings and scores on self-report characterization measures.
  6. Structural MRI and DTI data.
  7. Resting state FC at 1, 6 and 12 months post-treatment.

Clinical Study Identifier: NCT01511614

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National Institute on Drug Abuse
Baltimore, MD United States
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