A 4-year continuation and expansion of our existing study of the pulmonary effects of habitual use of marijuana is proposed to investigate the following: 1) the role of marijuana in respiratory tract carcinogenesis; 2) the effect of habitual marijuana smoking on pulmonary host defenses; and 3) mechanisms that might account for our observations of the association of marijuana with lung inflammation. Over a 4-year period, 32 smokers in each of the following smoking categories, marijuana only [MS], tobacco only [TS], marijuana plus tobacco [MTS] and nonsmokers [NS], will undergo fiberoptic bronchoscopy (using a new fluorescence endoscopic system which is sensitive in detecting severe bronchial dysplasia), auto-fluorescence-guided bronchial mucosal biopsies, bronchial washings, and bronchoalveolar lavage (BAL). Bronchial epithelial cells and tissue (obtained by fluorescence bronchoscopy), BAL fluid and alveolar macrophages (AMs) isolated therefrom will be used to accomplish the following specific objectives: 1) to assess the relative risk of smoking marijuana and tobacco, alone and in combination, for the development of moderate to severe dysplasia (a serious precursor lesion to bronchogenic carcinoma); 2) to determine whether marijuana smoking, on a per cigarette basis, activates the P4501A1 enzyme pathway (which converts polycyclic aromatic hydrocarbons present in the tar fraction of tobacco and marijuana smoke into active carcinogens) to a greater degree than tobacco smoking; 3) to extend the previous descriptive histopathological observations of bronchial epithelial changes in marijuana smokers in a mechanistic and molecular direction by studying specific genes and gene products thought relevant to human lung cancer progression; 4) to evaluate the effects of marijuana and tobacco smoking, singly and in combination, on the uptake, killing and destruction of bacteria by AMs, as well as the mechanisms associated with these anti- bacterial effects; 5) to determine the role of inflammatory cytokines, including macrophage-colony stimulating factor (M-CSF), interleukin-8 (lL-8), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-Beta 1, (TGF-Beta 1), as specific mediators of inflammation induced by smoking marijuana and/or tobacco; and 6) to determine whether the increased numbers of neutrophils which we have previously found in BAL fluid from smokers of marijuana and/or tobacco are activated, as reflected by their release into BAL fluid of increasing amounts of defensins and proteases that convert alpha 2-macroglobulin to its fast electrophoretic form.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003018-14
Application #
2116679
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1982-07-01
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
14
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kiertscher, Sylvia M; Gangalum, Pallavi R; Ibrahim, Grace et al. (2018) A Prospective Study of Humoral and Cellular Immune Responses to Hepatitis B Vaccination in Habitual Marijuana Smokers. J Neuroimmune Pharmacol 13:219-229
Roth, Michael D; Castaneda, Julie T; Kiertscher, Sylvia M (2015) Exposure to ?9-Tetrahydrocannabinol Impairs the Differentiation of Human Monocyte-derived Dendritic Cells and their Capacity for T cell Activation. J Neuroimmune Pharmacol 10:333-43
Castaneda, Julie T; Harui, Airi; Kiertscher, Sylvia M et al. (2013) Differential expression of intracellular and extracellular CB(2) cannabinoid receptor protein by human peripheral blood leukocytes. J Neuroimmune Pharmacol 8:323-32
Harui, Airi; Kiertscher, Sylvia M; Roth, Michael D (2011) Reconstitution of huPBL-NSG mice with donor-matched dendritic cells enables antigen-specific T-cell activation. J Neuroimmune Pharmacol 6:148-57
Sarafian, Theodore; Montes, Cindy; Harui, Airi et al. (2008) Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells. Toxicol Appl Pharmacol 231:282-90
Copersino, Marc L; Boyd, Susan J; Tashkin, Donald P et al. (2006) Quitting among non-treatment-seeking marijuana users: reasons and changes in other substance use. Am J Addict 15:297-302
Copersino, Marc L; Boyd, Susan J; Tashkin, Donald P et al. (2006) Cannabis withdrawal among non-treatment-seeking adult cannabis users. Am J Addict 15:8-14
Hashibe, Mia; Straif, Kurt; Tashkin, Donald P et al. (2005) Epidemiologic review of marijuana use and cancer risk. Alcohol 35:265-75
Boyd, Susan J; Tashkin, Donald P; Huestis, Marilyn A et al. (2005) Strategies for quitting among non-treatment-seeking marijuana smokers. Am J Addict 14:35-42
Roth, Michael D; Baldwin, Gayle C; Tashkin, Donald P (2002) Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. Chem Phys Lipids 121:229-39

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