A growing body of physiological evidence now exists to support a potential role for inhaled cannabis in the medical management of adults with chronic obstructive pulmonary disease (COPD), particularly as it may related to improving pulmonary function, alleviating the symptom of breathlessness and improving exercise endurance. The purpose of this randomized double-blind crossover trials is to evaluate the efficacy and physiological mechanism(s) of action of inhaled vaporized cannabis targeted to relief of physical activity-related breathlessness and exercise endurance in symptomatic patients with severe-to-very severe COPD.

Inclusion Criteria:

• GOLD stage III or IV COPD (i.e., post-β2-agonist FEV1 of 50% predicted or less)
• Self-reported cigarette smoking history ≥10 pack yrs
• Currently taking long-acting beta-2 agonists and long-acting antimuscarinic agents (LABA/LAMAs) with or without an inhaled corticosteroid
• Willing to abstain from cannabis smoking for ≥15 days prior to study participation (if applicable)
• Willing to abstain from non-study related cannabis smoking throughout the study period (if applicable)
• No change in medication dosage or frequency of administration, with no exacerbations or hospitalizations in the preceding 4 weeks

Exclusion Criteria:

• Presence of active and/or uncontrolled cardiopulmonary and/or musculoskeletal disease other than COPD that could contribute to breathlessness and exercise intolerance
• Hepatic or renal impairment
• Psychiatric history (other than depression and/or anxiety)
• History of epilepsy or convulsions;
• Lung cancer
• History of sensitivity to cannabis
• Use of levodopa, sildenafil and/or fentanyl
• Use of ketoconazole
• Use of regular high dose opioids (i.e., 30 mg of oral morphine equivalents/day)
• Known or suspected history of addiction/substance abuse based on CAGE-AID and SISAP scores (*note, patients may be recruited if they have a history of smoking cannabis)
• Positive urine toxicology for cannabinoids on screening
• Positive pregnancy urine test
• Subject cannot arrange to be accompanied home by a family member and/or friend during each treatment visit.