Chronic Cannabis Smoking, Oxidative Stress and the Pulmonary Innate Immune Response

Inclusion Criteria: INCLUSION CRITERIA for CANNABIS USING patient: Subjects will be eligible if they meet ALL of the following criteria: 1. Daily or near daily cannabis use (inhaled via joint/cigarette or pipe) equivalent to AT LEAST 20 "joint years" (number of joints/cigarettes per day multiplied by number of years during which cannabis was smoked) by self-report and validated through urine drug screen. 2. Never or limited exposure to inhaled tobacco products (equivalent to LESS THAN one "pack year" in a lifetime) by selfreport and validated through negative urine cotinine screen. 3. Capacity to answer screening questions and provide informed consent at time of interview, along with contact information INCLUSION CRITERIA for CONTROL patient: Subjects will be eligible if they meet all of the following: 1. No cannabis use ever by self-report, and validated through urine drug screen. 2. Never users of tobacco/cigarettes 3. Capacity to answer screening questions and provide informed consent at time of interview, along with contact information. Exclusion Criteria: EXCLUSION CRITERIA for CANNABIS USING patient: Subjects will be ineligible if they meet ANY of the following criteria: 1. LESS THAN near daily cannabis use (inhaled via joint/cigarette or pipe) equivalent to LESS THAN 20 "joint years" (number of joints/cigarettes per day multiplied by number of years during which cannabis was smoked) or a negative urine drug screen (for cannabis) 2. Inhaled tobacco product exposure EXCEEDING one "pack year" or a positive urine cotinine screen 3. Elevated AUDIT-C score: A 3 item questionnaire to identify subjects with alcohol use disorders. 4. Prior medical history of liver disease: cirrhosis, total bilirubin \> 2.0 mg/dL or albumin \<3 5. Prior medical history of myocardial infarction or congestive heart failure 6. Prior medical history of end-stage renal disease or serum creatinine \>3 mg/dL 7. Prior history of or current use of illicit drug use defined as a positive toxicology screen for opiates or cocaine 8. Prior history of diabetes mellitus 9. Prior history of chronic obstructive pulmonary disease (COPD) or asthma that is not clinically controlled (have not required systemic corticosteroids in the past month) 10. Prior history of HIV, not controlled or on medication 11. Peripheral white blood cell count of less than 3000 12. Acute worsening (\<7 days) in respiratory symptoms (such as change in cough frequency or sputum production, fever, dyspnea, abnormal chest radiograph), or room air pulse oximetry of \< 92% at rest or spirometry of \< 50% predicted for FEV1 and FVC 13. Use of systemic antibiotics for any reason in the past month (4 weeks) 14. Failure of a subject or the subject's substance abuse counselor to provide assent 15. Nutritional risk index of less than 95 16. Age \< 21 or \> 55 (using an age of 55 limits the likelihood of comorbid conditions that may increase the risk of adverse events with bronchoscopy) 17. Pregnancy 18. Decisionally challenged 19. Prisoners. EXCLUSION CRITERIA for CONTROL patient: Subjects will be ineligible to participate if they meet ANY of the following criteria: 1. History of inhaled cannabis exposure EXCEEDING one "joint year" or positive urine toxicology screen (for cannabis) 2. History of inhaled tobacco product exposure EXCEEDING one "pack year" or a positive urine cotinine screen 3. Elevated AUDIT-C score: A 3 item questionnaire to identify subjects with alcohol use disorders. 4. Prior medical history of liver disease: cirrhosis, total bilirubin \> 2.0 mg/dL or albumin \<3 5. Prior medical history of myocardial infarction or congestive heart failure 6. Prior medical history of end-stage renal disease or serum creatinine \>3 mg/dL 7. Prior history of or current use of illicit drug use defined as a positive toxicology screen for opiates or cocaine 8. Prior history of diabetes mellitus 9. Prior history of chronic obstructive pulmonary disease (COPD) or asthma that is not clinically controlled (have not required systemic corticosteroids in the past month) 10. Prior history of HIV, not controlled or on medication 11. Peripheral white blood cell count of less than 3000 12. Acute worsening (\<7 days) in respiratory symptoms (such as change in cough frequency or sputum production, fever, dyspnea, abnormal chest radiograph), or room air pulse oximetry of \< 92% at rest or spirometry of \< 50% predicted for FEV1 and FVC 13. Use of systemic antibiotics in the past month (4 weeks) 14. Failure of a subject or the subject's substance abuse counselor to provide assent 15. Nutritional risk index of less than 95 16. Age \< 21 or \> 55 17. Pregnancy 18. Decisionally challenged 19. Prisoners.