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Brain Nicotine Receptor Density in Veteran Smokers

Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Positron Emission Tomography

Phase: N/A

Status: Recruiting

Sponsored by: Department of Veterans Affairs

Official(s) and/or principal investigator(s):
Arthur L. Brody, MD, Principal Investigator, Affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Overall contact:
Robert Hubert, BA, Phone: (310) 478-3711, Ext: 44342, Email: robert.hubert@va.gov


Cigarette smoking is more prevalent among Veterans (27%) than the general U. S. population (21%). Smoking is common among people who use marijuana or caffeine heavily, and the use of menthol cigarettes is becoming increasingly common, affecting approximately 9% of the Veteran population. Recent research by our group and others indicates that heavy marijuana or caffeine use, or the use of predominantly menthol cigarettes, can alter brain nicotinic acetylcholine receptor (nAChR) densities. For the proposed study, brain imaging with PET scanning will be used to determine nicotine receptor densities in Veteran cigarette smokers with and without heavy marijuana or caffeine use, and in menthol and non-menthol Veteran smokers. Results of the proposed research may have implications for improving treatments for Veterans who smoke cigarettes and who have specific drug use co-morbidities or who use menthol cigarettes.

Clinical Details

Official title: Nicotinic Acetylcholine Receptor Density and Veteran Cigarette Smokers

Study design: Time Perspective: Prospective

Primary outcome: Rating scales, 2-FA PET scan, and MRI scan

Detailed description: Despite improvements in tobacco control, the prevalence of Tobacco Dependence (TD) remains high at 27% among Veterans and 21% among the general U. S. population (~46 million U. S. adults). Both co-morbid substance use and menthol cigarette preference are important issues contributing to greater severity of TD. Among smokers, a lifetime history of substance use/dependence is common and approximately 33% of all smokers use primarily menthol cigarettes, meaning that roughly 9% of Veterans smoke menthols. In addition to menthol cigarette usage being prevalent among Veterans, this problem is likely to worsen over time, because recent military deployments increase the chances of smoking initiation and marketing of menthol cigarettes is aimed at roughly the age group that comprises the active military. For substance use/dependence, marijuana (MJ) users are five times more likely than non-MJ users to smoke tobacco cigarettes, and regular caffeine users are twice as likely as non-caffeine users to smoke cigarettes. Cigarette smoking contributes greatly to morbidity and mortality among patients with drug (and alcohol) dependencies, making it vital to understand better the complex relationship between drug/alcohol dependence and brain nicotine receptor densities in cigarette smokers. Based on prior literature and pilot data collected during the previous Merit Review period, the primary hypotheses for the proposed research are that: 1) Participants who are heavy MJ users will have higher 4 2* nAChR densities in the thalami (and other brain regions) than participants who are not heavy MJ users, 2) Participants who are daily heavy caffeine users will have lower 4 2* nAChR densities in the thalami (and other regions) than participants who are not heavy daily caffeine users, 3) Densities of 4 2* nAChRs in the thalami (and other brain regions of interest) will be higher in menthol than non-menthol cigarette smokers, and 4) lesser severity of 4 2* nAChR up-regulation at baseline (along with clinical factors such as lesser severity of nicotine dependence) will be associated with better treatment outcomes in a standard smoking cessation program, including an improved likelihood of quitting and/or decreasing smoking. To test these hypotheses, cigarette smokers will be recruited through flyers posted at the VA Greater Los Angeles Healthcare System in areas where smokers are likely to be present. Participants will undergo the following sequence of procedures: (1) telephone/in-person screening, (2) a bolus-plus-continuous-infusion 2-FA positron emission tomography (PET) scanning session, (3) a structural magnetic resonance imaging scan within one week of the initial PET session, and (4) referral to a standard 12-week smoking cessation program. Rating scales for the determination of smoking-related symptoms will be collected before and during the PET scanning procedure. Smoking status and measures of nicotine exposure and metabolism will be collected during the study using participant reports, exhaled carbon monoxide (CO) levels, urine cotinine levels, and plasma nicotine, cotinine, and 3'-hydroxycotinine levels.


Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.


Inclusion Criteria:

- Must be a Veteran cigarette smoker, living within commuting distance of the VA

Greater Los Angeles (west Los Angeles VA campus)

- Healthy adult Veterans (18 to 65 years old) who are tobacco dependent cigarette

smokers (10 to 40 cigarettes per day) meeting criteria for Nicotine Dependence as defined by DSM-IV criteria109 and who want to quit smoking.

- Heavy marijuana or caffeine use (defined as using the equivalent of > 2 marijuana

cigarettes per week or the use of at least 3 coffee cup equivalents per day) for at least the past 6 months or no heavy drug/alcohol use.

- Ability to read, write, and give voluntary informed consent.

- An exhaled CO > 8 ppm during the study screening visit to verify smoking status.

Exclusion Criteria:

- Any Axis I diagnosis (including mood, anxiety, and psychotic disorders) other than

Nicotine, Marijuana, or Caffeine Dependence within the past 1 year.

- A current diagnosis (within the past month) of other substance abuse/dependence

diagnoses (such as cocaine, amphetamine, or opiates). (Length of abstinence will be verified through participant interview and a chart review at the initial study visit, which typically includes information about substance abuse treatment history and objective verification with breathalyzer and/or urine toxicology screens). Occasional drug/alcohol use not meeting criteria for abuse/dependence will not be exclusionary.

- Any current medication or any history of a medical condition that might affect the

central nervous system at the time of scanning (e. g., current treatment with a psychotropic medication, or history of severe head trauma with loss of consciousness, epilepsy, or other neurological diseases).

- The combination of both heavy marijuana and caffeine use.

- Unstable cardiovascular disease, severe liver disease, or renal insufficiency, which

might make tolerating study procedures difficult. Routine history and physical examination will be performed at the initial screening visit to insure that participants meet study criteria (Section D4).

- Pregnancy (urine pregnancy tests will be obtained on all women of childbearing

potential) due to the theoretical risk of radiation exposure to the fetus.

Locations and Contacts

Robert Hubert, BA, Phone: (310) 478-3711, Ext: 44342, Email: robert.hubert@va.gov

VA Greater Los Angeles Healthcare System, West Los Angeles, CA, West Los Angeles, California 90073, United States; Recruiting
Robert Hubert, BA, Phone: 310-478-3711, Ext: 44342, Email: robert.hubert@va.gov
Arthur L. Brody, MD, Principal Investigator
Additional Information

Related publications:

Potenza MN, Brody AL. Commentary on Boileau et al. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions. Addiction. 2013 May;108(5):964-5. doi: 10.1111/add.12119.

Jasinska AJ, Zorick T, Brody AL, Stein EA. Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans. Neuropharmacology. 2014 Sep;84:111-22. doi: 10.1016/j.neuropharm.2013.02.015. Epub 2013 Mar 6. Review.

Brody AL, Mukhin AG, Stephanie Shulenberger, Mamoun MS, Kozman M, Phuong J, Neary M, Luu T, Mandelkern MA. Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density. Neuropsychopharmacology. 2013 Jul;38(8):1548-56. doi: 10.1038/npp.2013.53. Epub 2013 Feb 21.

Jarcho JM, Feier NA, Bert A, Labus JA, Lee M, Stains J, Ebrat B, Groman SM, Tillisch K, Brody AL, London ED, Mandelkern MA, Mayer EA. Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain. Pain. 2013 Jul;154(7):987-96. doi: 10.1016/j.pain.2013.02.026. Epub 2013 Mar 5.

Storage S, Mandelkern MA, Phuong J, Kozman M, Neary MK, Brody AL. A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability. Psychiatry Res. 2013 Dec 30;214(3):415-21. doi: 10.1016/j.pscychresns.2013.07.010. Epub 2013 Oct 19.

Xu J, Fregni F, Brody AL, Rahman AS. Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers. Front Psychiatry. 2013 Sep 20;4:112. doi: 10.3389/fpsyt.2013.00112. eCollection 2013.

Le Foll B, Guranda M, Wilson AA, Houle S, Rusjan PM, Wing VC, Zawertailo L, Busto U, Selby P, Brody AL, George TP, Boileau I. Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+-PHNO PET study in humans. Neuropsychopharmacology. 2014 Jan;39(2):415-24. doi: 10.1038/npp.2013.209. Epub 2013 Aug 19.

Starting date: January 2013
Last updated: May 13, 2015

Page last updated: August 23, 2015

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