Brain Nicotine Receptor Density in Veteran Smokers

NCT01721473 | Completed Results

• 1 other identifier: NURA-02-11S
• Study Type: observational
• Target: 184
• Locations: 1 country
• Sites: 2

Brief Summary

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 the 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.

Conditions

Positron Emission Tomography

Keywords

Tobacco; Positron Emission Tomography; Marijuana; Caffeine; Menthol

Outcome Measures

Primary Outcomes (1)

• PET Scan, Rating Scales

  Vt/fp values (indicating relative densities of alpha4beta2 nicotinic acetylcholine receptors in different brain regions) in various brain regions - can also be referred to as mL/cm3.

  Primary outcome measures will be determined over approximately 3 weeks

Study Arms (6)

cigarette smokers with heavy marijuana use

With heavy marijuana use

Other: positron emission tomography scan

cigarette smokers with heavy caffeine use

with heavy caffeine use

Other: positron emission tomography scan

cigarette smokers w/o heavy caffeine and marijuana use

cigarette smokers without the heavy use of marijuana or caffeine

Other: positron emission tomography scan

non-smokers

not a regular cigarette user

Other: positron emission tomography scan

cigarette smokers with non-menthol cigarette preference

non-menthol cigarette preference

Other: positron emission tomography scan

cigarette smokers with menthol cigarette preference

menthol cigarette preference

Other: positron emission tomography scan

Interventions

positron emission tomography scan OTHER

2-FA positron emission tomography scan

cigarette smokers w/o heavy caffeine and marijuana use; cigarette smokers with heavy caffeine use; cigarette smokers with heavy marijuana use; cigarette smokers with menthol cigarette preference; cigarette smokers with non-menthol cigarette preference; non-smokers

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Veterans who are cigarette smokers (10 to 40 cigarettes per day) who either use significant amounts of caffeine or marijuana (or who have little or no such use).

You may qualify if:

• Must be a Veteran cigarette smoker, living within commuting distance of the VA San Diego Healthcare System
• 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.

You may not qualify if:

• Any Axis I diagnosis (including mood, anxiety, and psychotic disorders) other than Nicotine, Marijuana, or Caffeine Dependence within the past 1 year.
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

Location

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

Location

Related Publications (17)

• 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.

  PMID: 23587083 BACKGROUND

• 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.

  PMID: 23474015 BACKGROUND

• 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.

  PMID: 23429692 BACKGROUND

• 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.

  PMID: 23582152 BACKGROUND

• 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.

  PMID: 24148908 BACKGROUND

• 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.

  PMID: 24065930 BACKGROUND

• 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.

  PMID: 23954846 BACKGROUND

• 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.

  PMID: 26303184 BACKGROUND

• 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.

  PMID: 27613888 BACKGROUND

• 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.

  PMID: 28322859 BACKGROUND

• 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.

  PMID: 23171716 RESULT

• 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.

  PMID: 24850280 RESULT

• 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.

  PMID: 25551240 RESULT

• 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.

  PMID: 25868069 RESULT

• 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.

  PMID: 26272810 RESULT

• 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.

  PMID: 27370018 RESULT

• 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.

  PMID: 28262740 RESULT

Biospecimen

Retention: NONE RETAINED

None retained.

MeSH Terms

Conditions

Marijuana Abuse

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Arthur Brody
• Organization: VA San Diego Healthcare System

arthur.brody@va.gov

8585528585

Study Officials

• Arthur L Brody, MD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2012
• First Posted: November 5, 2012
• Study Start: January 1, 2012
• Primary Completion: June 30, 2016
• Study Completion: June 30, 2016
• Last Updated: October 7, 2019
• Results First Posted: October 7, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)