Poor appetite is one of the subjective symptoms that cancer patients find most frustrating, and resulting cachexia is a common cause of death from cancer. In addition, nausea is a frequent side effect of cancer treatment. Oral delivery of the cannabinoid agonist dronabinol is approved by the FDA as both an anti-emetic agent and an appetite-enhancer. Its clinical utility, however, is limited by extensive first pass metabolism and resulting inconsistent oral bioavailability. In Phase I of this grant application, we have demonstrated the ability to form high purity, small particle size aerosols of dronabinol for reliable systemic delivery through inhalation. These aerosols can be produced by simple, breath-actuated devices. In Phase II of the grant, we now propose to prove the consistency of systemic absorption of these aerosols when inhaled by dogs. In addition, we plan to conduct the animal toxicology experiments and produce the clinical trial materials required to initiate human studies of inhaled dronabinol. Accomplishment of these goals of Phase II will lead directly to human clinical testing of a cost effective, commercially viable dronabinol inhalation delivery system. Beyond providing for improved dronabinol delivery, this drug product addresses a major unmet need in the cancer area: an appetite-enhancing and nausea-decreasing medication that works rapidly and does not require painful injection or for patients with gastrointestinal distress to consume oral medication.
