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:

• 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.
• 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.
• 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:

• No cannabis use ever by self-report, and validated through urine drug screen.
• Never users of tobacco/cigarettes
• 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:

• 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)
• Inhaled tobacco product exposure EXCEEDING one "pack year" or a positive urine cotinine screen
• Elevated AUDIT-C score: A 3 item questionnaire to identify subjects with alcohol use disorders.
• Prior medical history of liver disease: cirrhosis, total bilirubin > 2.0 mg/dL or albumin \<3
• Prior medical history of myocardial infarction or congestive heart failure
• Prior medical history of end-stage renal disease or serum creatinine >3 mg/dL
• Prior history of or current use of illicit drug use defined as a positive toxicology screen for opiates or cocaine
• Prior history of diabetes mellitus
• Prior history of chronic obstructive pulmonary disease (COPD) or asthma that is not clinically controlled (have not required systemic corticosteroids in the past month)
• Prior history of HIV, not controlled or on medication
• Peripheral white blood cell count of less than 3000
• 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
• Use of systemic antibiotics for any reason in the past month (4 weeks)
• Failure of a subject or the subject's substance abuse counselor to provide assent
• Nutritional risk index of less than 95
• 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)
• Pregnancy
• Decisionally challenged
• Prisoners.

EXCLUSION CRITERIA for CONTROL patient: Subjects will be ineligible to participate if they meet ANY of the following criteria:

• History of inhaled cannabis exposure EXCEEDING one "joint year" or positive urine toxicology screen (for cannabis)
• History of inhaled tobacco product exposure EXCEEDING one "pack year" or a positive urine cotinine screen
• Elevated AUDIT-C score: A 3 item questionnaire to identify subjects with alcohol use disorders.
• Prior medical history of liver disease: cirrhosis, total bilirubin > 2.0 mg/dL or albumin \<3
• Prior medical history of myocardial infarction or congestive heart failure
• Prior medical history of end-stage renal disease or serum creatinine >3 mg/dL
• Prior history of or current use of illicit drug use defined as a positive toxicology screen for opiates or cocaine
• Prior history of diabetes mellitus
• Prior history of chronic obstructive pulmonary disease (COPD) or asthma that is not clinically controlled (have not required systemic corticosteroids in the past month)
• Prior history of HIV, not controlled or on medication
• Peripheral white blood cell count of less than 3000
• 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
• Use of systemic antibiotics in the past month (4 weeks)
• Failure of a subject or the subject's substance abuse counselor to provide assent
• Nutritional risk index of less than 95
• Age \< 21 or > 55
• Pregnancy
• Decisionally challenged
• Prisoners.