Study Results
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View full resultsBasic Information
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COMPLETED
184 participants
OBSERVATIONAL
2012-01-01
2016-06-30
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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cigarette smokers with heavy marijuana use
With heavy marijuana use
positron emission tomography scan
2-FA positron emission tomography scan
cigarette smokers with heavy caffeine use
with heavy caffeine use
positron emission tomography scan
2-FA positron emission tomography scan
cigarette smokers w/o heavy caffeine and marijuana use
cigarette smokers without the heavy use of marijuana or caffeine
positron emission tomography scan
2-FA positron emission tomography scan
non-smokers
not a regular cigarette user
positron emission tomography scan
2-FA positron emission tomography scan
cigarette smokers with non-menthol cigarette preference
non-menthol cigarette preference
positron emission tomography scan
2-FA positron emission tomography scan
cigarette smokers with menthol cigarette preference
menthol cigarette preference
positron emission tomography scan
2-FA positron emission tomography scan
Interventions
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positron emission tomography scan
2-FA positron emission tomography scan
Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
65 Years
ALL
No
Sponsors
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VA Office of Research and Development
FED
Responsible Party
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Principal Investigators
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Arthur L Brody, MD
Role: PRINCIPAL_INVESTIGATOR
VA San Diego Healthcare System, San Diego, CA
Locations
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VA San Diego Healthcare System, San Diego, CA
San Diego, California, United States
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
West Los Angeles, California, United States
Countries
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References
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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. No abstract available.
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.
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.
Zanchi D, Brody AL, Montandon ML, Kopel R, Emmert K, Preti MG, Van De Ville D, Haller S. Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate. Addict Biol. 2015 Nov;20(6):1033-41. doi: 10.1111/adb.12292. Epub 2015 Aug 25.
Brody AL, Zorick T, Hubert R, Hellemann GS, Balali S, Kawasaki SS, Garcia LY, Enoki R, Abraham P, Young P, McCreary C. Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial. Nicotine Tob Res. 2017 Jan;19(1):68-76. doi: 10.1093/ntr/ntw190. Epub 2016 Aug 3.
Xie J, Douglas PK, Wu YN, Brody AL, Anderson AE. Decoding the encoding of functional brain networks: An fMRI classification comparison of non-negative matrix factorization (NMF), independent component analysis (ICA), and sparse coding algorithms. J Neurosci Methods. 2017 Apr 15;282:81-94. doi: 10.1016/j.jneumeth.2017.03.008. Epub 2017 Mar 18.
Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, Mandelkern MA. Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. Int J Neuropsychopharmacol. 2013 Jun;16(5):957-66. doi: 10.1017/S1461145712001022. Epub 2012 Nov 21.
Brody AL, Mukhin AG, Mamoun MS, Luu T, Neary M, Liang L, Shieh J, Sugar CA, Rose JE, Mandelkern MA. Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial. JAMA Psychiatry. 2014 Jul 1;71(7):797-805. doi: 10.1001/jamapsychiatry.2014.138.
Zorick T, Mandelkern MA, Brody AL. A naturalistic study of the association between antidepressant treatment and outcome of smoking cessation treatment. J Clin Psychiatry. 2014 Dec;75(12):e1433-8. doi: 10.4088/JCP.14m09012.
Brody AL, McClernon FJ. Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology. 2015 May;40(6):1309-10. doi: 10.1038/npp.2015.31. No abstract available.
Dubroff JG, Doot RK, Falcone M, Schnoll RA, Ray R, Tyndale RF, Brody AL, Hou C, Schmitz A, Lerman C. Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. J Nucl Med. 2015 Nov;56(11):1724-9. doi: 10.2967/jnumed.115.155002. Epub 2015 Aug 13.
Brody AL, Hubert R, Mamoun MS, Enoki R, Garcia LY, Abraham P, Young P, Mandelkern MA. Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use. Psychopharmacology (Berl). 2016 Sep;233(17):3249-57. doi: 10.1007/s00213-016-4367-x. Epub 2016 Jul 1.
Brody AL, Hubert R, Enoki R, Garcia LY, Mamoun MS, Okita K, London ED, Nurmi EL, Seaman LC, Mandelkern MA. Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study. Neuropsychopharmacology. 2017 Jul;42(8):1630-1639. doi: 10.1038/npp.2017.48. Epub 2017 Mar 6.
Other Identifiers
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NURA-02-11S
Identifier Type: -
Identifier Source: org_study_id
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