Nicotine Withdrawal Symptoms and Smoking Relapse
- 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.
- To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.
- 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.
- 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.
|Study Design:||Time Perspective: Cross-Sectional|
|Official Title:||Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers|
- Change in BOLD signal and FC related to task parameters, Behavioral performance, and Self-reported craving, withdrawal symptoms and mood/affect. [ Time Frame: Each Scan Visit ] [ Designated as safety issue: No ]
- Smoking Abstinence as Determined by Self-Reported Tobacco Use, Urine Cotinine, and Breath CO. [ Time Frame: At Study Visits ] [ Designated as safety issue: No ]
- MRS for glutamate concentration, Plasma ACTH and cortisol, Resting state CBF, ERP and EEG measures, craving and physiological responses to physical drug cues, self-report characterization measures, & structural MRI and DTI data. [ Time Frame: At Study Visits ] [ Designated as safety issue: No ]
|Study Start Date:||December 2011|
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. The protocol will focus on the anhedonia, negative affect, inhibitory control deficits and impulsive decision making which accompany acute nicotine withdrawal in humans. The extent to which these acute withdrawal- related processes predict the success of smoking cessation treatment will be assessed. Secondary objectives are to understand the neurobiological basis of responsivity to nicotine replacement with respect to acute nicotine withdrawal symptoms and to examine the neurobiological mechanisms underlying motivation to quit smoking and the interaction between motivation to quit and symptoms which arise during acute withdrawal from nicotine.
We aim to recruit 85 nicotine-dependent individuals aged 18 to 55 years who are currently seeking treatment for smoking cessation (treatment-seeking smokers) and 35 nicotine dependent individuals aged 18-55 years who are not currently seeking treatment for smoking cessation (non-treatment seeking smokers). Nicotine dependency will based on a urine cotinine (NicAlert) level of 4 or higher and a history of smoking consistently for at least one year.
The study will be a within (nicrotine deprivation) between (treatment-seeking status) subjects double blind placebo controlled design. All participants will complete two scanning sessions, each preceded by a 36 hour smoking abstinence period. During one abstinence period and scanning session participants will wear a dose-matched nicotine patch (non-deprived), and during the other abstinence period and scanning session, a placebo-patch (nicotine-deprived). Following participation in both scan sessions treatment-seeking participants will commence 12 weeks of treatment involving daily varenicline administration with weekly counseling. Follow- up assessments will be conducted with treatment-seeking smokers at 1, 6, and 12 months after their last treatment visit.
Primary outcome measures:
- Change in BOLD signal and FC related to task parameters, between drug condition.
- Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity and impulsive decision making (e.g., reaction time, error rate, hit rate, reward bias).
- Self-reported craving, withdrawal symptoms and mood/affect.
- Smoking abstinence as determined by self - reported tobacco use, urine cotinine, and breath CO.
Secondary outcome measures:
- MRS for glutamate concentration.
- Plasma ACTH and cortisol.
- Resting state CBF from ASL.
- ERP and EEG measures.
- Ratings and scores on self-report characterization measures.
- Structural MRI and DTI data.
- Resting state FC at 1, 6, and 12 months post- treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01511614
|Contact: Elliot Stein, Ph.D.||(443) email@example.com|
|United States, Maryland|
|National Institute on Drug Abuse||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: For more information contact Mathew's Media Group Recruiting 800-535-8254 firstname.lastname@example.org|
|Principal Investigator:||Elliot Stein, Ph.D.||National Institute on Drug Abuse (NIDA)|