Brain Imaging in Tobacco Smokers During a Quit Attempt
Brain Imaging in Tobacco Smokers During a Quit Attempt
The proposed study will help fill gaps in existing research by determining if
 nicotine-dependent cigarette smokers show changes in α7 nicotinic acetylcholine receptor
 (nAChR) availability when compared to matched historical controls using positron emission
 tomography (PET) imaging and the radioactive ligand [18F]-ASEM
 (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6 [18F]fluorodibenzo[b,d]thiophene 5,5-dioxide), an α7
 nAChR antagonist. The study will also explore whether α7 nAChR availability influences
 clinically relevant measures of tobacco abstinence (e.g., withdrawal and craving, cognitive
 impairment), self-reported cigarettes per day, and time to relapse during an 8-day quit
 attempt during which smokers can receive escalating payments contingent upon providing
 objective evidence (breath CO and urinary cotinine) of smoking abstinence.
The primary objective of this basic clinical research study is to examine the role of the
 alpha7-nicotinic acetylcholine receptors (nAChRs) in tobacco use disorder. nAChRs are the
 primary site of action for nicotine (the main psychoactive component of tobacco). The most
 common types of nAChRs are heteromeric nAChRs containing beta2 subunits and homomeric nAChRs,
 which contain only alpha7 subunits. It is currently unknown if or how chronic tobacco use
 affects alpha7 nAChR in humans. The investigators' working hypothesis is brain alpha7 nAChR
 density associated with chronic nicotine exposure and the development of tobacco use disorder
 may be influence severity of tobacco craving and withdrawal during early smoking abstinence.

 Proposed group sample sizes are 18 tobacco smokers (accrual) and 18 nonsmokers (drawn from
 historical and contemporary controls in ongoing studies). Media-recruited male and female
 heavy smokers will be assessed for study inclusion/exclusion criteria using a structured
 diagnostic interview and a standard battery of instruments, as well as a medical exam to
 determine general health. Study candidates also provide breath and urine samples to determine
 biomarkers of tobacco use (breath carbon oxide and urinary cotinine levels), other drug use
 (breath alcohol and urine toxicology) and for females a pregnancy test. To ensure there are a
 sufficient number of subjects, 60 subjects will be screened for study eligibility and
 assessed for matching criteria (age, race and sex). Groups (smokers vs. non-smokers) will
 include equal numbers of males and females. In addition, male and female smokers will be
 matched for tobacco use disorder severity using symptom counts (DSM 5).

 Eligible subjects will be enrolled in an outpatient protocol completed at the Behavioral
 Pharmacology Research Unit (BPRU) at the Johns Hopkins Bayview Medical Center, and at the
 Johns Hopkins Hospital (JHH) PET imaging Center. Abstinent smokers (as verified by CO and
 cotinine, see below) will complete an magnetic resonance imaging (MRI) scan and a PET scan
 with the alpha-7 nAChR radiotracer [18F]-ASEM. Matched historical controls will have
 completed the MRI and PET scans previously.

 Tobacco users will receive contingency management incentive payments for verified smoking
 abstinence (Intervention 2, behavioral counseling). Smokers will continue in the study after
 the PET scan and complete an 8-day practice quit attempt. To evaluate smoking abstinence and
 lapse behavior, smokers will be asked to complete study six visits with a practice quit
 attempt. Smoker will receive the incentive intervention for smoking abstinence. At each
 visit, smokers will provide carbon monoxide (CO) and urine samples, and complete assessment
 instruments to self-report on daily symptoms of nicotine withdrawal and craving, and number
 of cigarettes smoked. The incentive intervention is a validated, established intervention for
 smoking cessation. At each visit, smokers will receive escalating incentive payments
 contingent upon provision of samples that meet study defined abstinence criteria. The
 incentive earning schedule starts at $9 on day 1 of abstinence and increases by $1.50 for
 each day of verified abstinence to $19.50 on day 8. To boost the incentive for abstinence,
 provision of samples that meet bonus abstinence (cotinine <100 ng/ml day 8) results
 additional $10 or $20 bonus payments. The incentive earnings schedule includes allowance for
 a slip, and a reset contingency to allow smokers to retry the quit attempt and complete the
 study. This incentive earnings schedule with resets is of high magnitude to reinforce
 abstinence, and increase participant retainment. The number of days in the quit attempt (8)
 yields a sufficient sample to examine both withdrawal and biomarkers (CO and cotinine) to
 quantify number of days in which use of any nicotine occurred vs. days participants were
 compliant in maintaining abstinence. These data will be utilized to explore the relationship
 of alpha7-nAChR availability to these clinically meaningful measures of tobacco use and
 abstinence.
Inclusion Criteria:

 -  Subjects must be healthy volunteers

 -  Regular tobacco smokers for a period of 2 or more years

 -  Positive breath carbon monoxide (CO)

 -  Cotinine positive urine test

 -  Meet DSM-V criteria for tobacco use disorder.

 Exclusion Criteria:

 -  Meets DSM-5 criteria for alcohol use disorder or substance use disorder (excluding
 tobacco use disorder)

 -  Meets DSM-5 Psychiatric Disorder; in or in need of treatment

 -  History of seizures, seizure disorder or closed head trauma

 -  HIV positive

 -  Weight > 350 lbs

 -  < 5th grade reading level

 -  Recent use of smoking cessation products

 -  If female: pregnant, lactating, planning pregnancy; positive urine pregnancy screen

 -  Any condition which would preclude MRI

 -  Radiation exposure in the last year that when combined with the study protocol would
 exceed the annual limits.