Nicotine Dependence
Conditions
Keywords
Smoking Cessation, fMRI, e-Cigarettes, Natural History
Brief summary
Background: \- Smoking is a difficult habit to quit, and some people find it more difficult to quit than others do. Nicotine is the substance in cigarettes that makes smoking so addictive. Nicotine changes some patterns of brain activity, and smokers have differences in brain activity when compared to non-smokers. Some genes make it more likely that a person will become addicted to smoking. Researchers want to study how nicotine interacts with genes and brain activity. This may help develop better treatments to help people quit smoking. Objectives: \- To develop a test of nicotine dependence, using brain activity and genetic analysis, which may be useful in predicting success in smoking cessation and in the development of new smoking cessation treatment targets. Eligibility: * Main group: Current smokers between 18 and 55 years of age who are seeking treatment to quit. * Comparison group: Current smokers between 18 and 55 years of age who are not seeking to quit. * Comparison group: Healthy former smokers between 18 and 55 years of age. * Comparison group: Healthy nonsmoking volunteers between 18 and 55 years of age. Design: * Participants will be screened with a physical exam and medical history. Blood samples will be collected. * The three comparison groups will have one magnetic resonance imaging (MRI) scan session. They will have tests of thinking, concentration, and memory both inside the scanner, and while sitting in front of a computer. * Current smokers who are trying to quit must be willing to undergo a course of nicotine treatment that includes weekly counseling (for 12 weeks) and e-cigarettes. Participants will attempt smoking abstinence and will have a total of 6 MRI scanning sessions. They will do thinking, concentration, and memory tasks inside and outside of the scanner. * For smokers, the first scanning session will take place before they attempt to quit. This will be a baseline scan. The second scanning session will take place 48 hours after having their last real cigarette. After this scan, they will use electronic cigarettes to help quit their habit. * After using e-cigarettes for two weeks, smokers will have a third scan session.. They will then gradually taper their use of the electronic cigarettes over the course of three weeks, at which point they will be nicotine abstinent. * After about 5 weeks of abstinence, they will have the fourth scan. The fifth scan will be approximately 6 months after start of the study, and the final scan will take place at about 1 year from the study start. * Smokers will continue to receive support on quitting smoking until the study ends at about 1 year.
Detailed description
Objective: To develop a neuroimaging/genetic/epigenetic biomarker of nicotine dependence severity that may be useful in predicting success in smoking cessation and in development of new smoking cessation treatment targets. Further, by evaluating those who vape nicotine, findings will determine whether biomarkers differ between those who smoke or vape, allowing for the development of cessation strategies that relate to preferred nicotine delivery. Study population: Four groups will be studied: target group of treatment seeking smokers/vapers; nontreatment seeking current smokers/vapers; never smokers/never vapers and former smokers. We estimate that we will need n=50/subgroup completers to have sufficient power to develop the brain/genetics biomarkers. Design: This study consists of a 4 group between/within subject design. The experimental group will proceed in 4 phases: Baseline (scan 1), peak withdrawal (scan 2), stable on nicotine replacement (scan 3), and complete abstinence (scans 4-6). Counseling will start after the first scan session and will generally continue weekly until scan 4 (about 12 weeks). After scan 4, therapeutic support will be provided at least monthly via phone until completion of the protocol. The non-treatment seeker comparison group will be scanned twice; at baseline (scan 1) and at peak withdrawal (scan 2). Each of the non-nicotine user comparison groups (non-nicotine users and Ex-smokers) will be scanned only at baseline (scan 1). Genetic and epigenetic markers will be obtained in all groups. Outcome measures: Network and multivariate pattern analysis, behavior on a decision making task and task based and resting state blood oxygen level-dependent (BOLD) activation in neural circuits relevant to nicotine addiction during fMRI scanning. Secondary outcomes include BOLD response comparisons between nicotine replacement and typical nicotine use and genetic markers of nicotine addiction and relapse susceptibility.
Interventions
None listed
Sponsors
National Institute on Drug Abuse (NIDA)
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: All participants must: 1. Be between the ages of 18-60. Assessment tool(s): Edinburgh Handedness Inventory. Although left-handed individuals will not be excluded, we will track handedness. Justification: Some of the neural processes assessed in this protocol may be lateralized in the brain. In order to assess potential variance, participants handedness will be documented. 2. Be in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a medical history and physical examination with a qualified IRP clinician. 3. Be free of active DSM-IV dependence, on alcohol or any drug except nicotine. Past active dependence is acceptable provided it is at least two years in the past. Those with past dependence on substances other than alcohol or marijuana may not have any current use (past 6 months) of the substance on which they were dependent. Individuals with past dependence on either alcohol or marijuana who report current use of the previously dependent substance may be included, provided they do not currently meet any criteria for dependence, with the exception of tolerance. MAI may exclude on a case-by-case basis for heavy alcohol or drug use not meeting dependence criteria but likely to interfere with data quality. Justification: Dependence on other substances (drugs or alcohol) may result in unique CNS deficits that could confound results and introduce excessive variance. Assessment tool(s): The SCID and/or the Mini International Neuropsychiatric Interview (M.I.N.I) and clinical substance abuse/dependence assessment. While recreational/intermittent use of alcohol and/or marijuana will be tolerated in all participant groups, individuals will be excluded if they meet current or recent (within 2 years) DSM-IV diagnostic criteria for dependence on any substances. A positive drug test for marijuana will not be exclusionary as long as participants have not used in the 24hrs preceding the imaging visits. In the event of a positive drug test for marijuana, self-reports of current marijuana use will be used to differentiate intermittent/infrequent from chronic/frequent users. 4. Be able to abstain from alcohol 24hrs before each of the imaging sessions and able to abstain from caffeine 24hrs before each session. Justification: Alcohol and caffeine modulate neural functioning in a way that would complicate data interpretation. Assessment tool(s): Self-report and breathalyzer. 5. For the treatment and non-treatment seeking groups, must have a urine cotinine level corresponding to smoker/nicotine user status for the specific test being used (typically corresponding to a urine cotinine above about 200 ng/ml) and have been smoking or vaping consistently for at least the past year (excluding quit attempts). Based on the correlation between self-reported cpd/FTND and urine cotinine levels \[85a, 85b\], a single inclusion criterion will be easier to manage and provide adequate characterization of nicotine dependent participants. Urine cotinine level provides a biomarker that does not rely on self-report/memory. Quit attempts will be assessed via clinical interview and judgment. Justification: The present protocol is interested in neurobiological mechanisms that underlie nicotine dependence-induced plasticity and is thus contingent on the presence of nicotine dependence. Assessment tool(s): Self-report, commercial urine cotinine test corresponding to smoker/nicotine user status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml. 6. For the treatment and non-treatment seeking groups, must be willing to attempt an acute abstinence period lasting approximately 48 hours. 7. For the treatment seeking group, be actively seeking treatment for nicotine cessation and willing to engage in 12-weeks of treatment involving weekly counseling sessions, as well as follow-up imaging and behavioral assessments following treatment onset. 8. For the ex-smoker group, must have smoked approximately 8 or more cigarettes per day for at least 1 year, and have remained abstinent continuously for at least the last 12 months. Justification: While serum cotinine level has been shown to be a more accurate measure of cigarette smoking than CPD \[85c\], it is impossible in the current design to collect retroactive serum cotinine levels from exsmokers. Instead, CPD must be equated with the urine cotinine levels of current treatment and nontreatment seeking groups. The low-end cotinine level for the inclusion of smokers/vapers in this protocol is about 200 ng/mL. In adult smokers, a nicotine intake of approximately 1 mg can be estimated from a blood cotinine level of 12.5 ng/mL) \[85d\]. Thus, to have achieved a blood cotinine level of 200ng/mL, ex-smokers would have to self-report consumption of 16 mg of nicotine per day which equates to approximately 8 CPD (0.36-2.62 mg nicotine yield per cigarette \[85e\]. Given these calculations, the inclusion criterion for the ex-smoker group has been lowered to 8 CPD. Assessment tool(s): Self-report, commercial urine cotinine test corresponding to non-smoker status for the specific test being used, typically corresponding to a urine cotinine under about 20 ng/ml, CO \< 6. 9. For the non-smoking/vaping control group, less than 20 times of lifetime use of nicotine containing products and vaping of non-nicotine containing products, none in past year and no history of daily nicotine use. Justification: Minimal nicotine exposure in the control group is required to assess differences between controls and the nicotine groups. Assessment tool(s): Self-report, commercial urine cotinine test corresponding to non-smoker status for the specific test being used, typically corresponding to a urine cotinine under about 20 ng/ml, CO \< 6.
Exclusion criteria
3.3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in BOLD signal and functional connectivity related to task parameters, between drug conditions (i.e. on and off nicotine) and between groups | each scan visit | 1\) Change in BOLD signal and functional connectivity related to task parameters, between drug conditions (i.e. on and off nicotine) and between groups: will provide important insight into the neurobiological mechanisms underlying acute and chronic nicotine withdrawal, in particular those related to anhedonia, negative affect, cognitive control and impulsive decision making. |
| Genetic and epigenetic data | each scan visit | 2\) Genetic and epigenetic data. These data will be included into the network and pattern classification models discussed above as features in the classifier. They will also be used as regressors, covariates or dichotomous variable in the above BOLD task analysis. |
| Resting state MRI at follow-up | each scan visit | 3\) Resting state MRI at follow-up. Resting state MRI will be assessed between- and within- groups as a function of relapse status and time since last treatment visit at each of the follow-up time-points (4 weeks, 3, 6 and 12 months). These data will be entered into the network and pattern classification models discussed above. This will allow us to address the following questions:i. What characteristics of rsFC are associated with treatment success (vs. failure)? ii. Are there characteristics of rsFC that vary as a function of time post-treatment in successfully abstinent individuals? |
| Behavioral performance on each task | each scan visit | 4\) Behavioral performance on each of the tasks assessing working memory, attention, processing speed, inhibitory control processes, cognitive control, reward responsiveness, amygdala, striatal, and impulsive decision making (e.g., reaction time, error rate, hit rate, reward bias): will provide task-related parameters necessary for analysis of BOLD and resting state data. Performance data will function as a secondary outcome by providing behavioral validation of acute and chronic nicotine withdrawal effects. |
| Self-reported craving, withdrawal symptoms & mood/affect | each scan visit | 5\) Self-reported craving, withdrawal symptoms and mood/affect: will be employed as regressors in the analysis of task and resting BOLD data. They will also provide the primary means of validating the acute nicotine withdrawal manipulation. |
| Smoking status at 4wks, 3, 6 and 12 months. | each scan visit | 6\) Smoking status at 4 weeks, 3, 6 and 12 months: Smoking status (relapse vs. abstinent) at each of the follow-up time points will be based on 7-day point prevalence defined as no smoking (not even a puff) or use of any tobacco products for the past 7 days. This is a standard method of assessing abstinence and dichotomizing relapse status at follow-up. Whenever abstinence at follow-up is assessed in-person, self-reported abstinence will be corroborated with breath COand urine cotinine levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2) Structural MRI and DTI data | each visit | 2\) Structural MRI and DTI data |
| 1) Ratings and scores on self-report characterization measures | each visit | 1\) Ratings and scores on self report characterization measures |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAmy C Janes, Ph.D.
National Institute on Drug Abuse (NIDA)
Outcome results
None listed