?9-tetrahydrocannabinol (?9-THC) has been shown to alleviate marijuana withdrawal symptoms and thus has potential for treating cannabinoid dependence. However, the bioavailability of ?9-THC administered orally is poor and variable. In addition, it also requires drug administration several times a day. Formulations to improve bioavailability and/or to reduce dosing frequency would be expected to improve the therapeutic effectiveness of ?9-THC. ? ? In Phase I, our technical objectives are to develop improved oral and/or depot formulations of ?9-THC based on biopharmaceutical rationale, and select a formulation that is stable with acceptable in vitro controlled release characteristics. ?9-THC is very hydrophobic and oxygen-sensitive, both factors that are challenges in making formulations that are orally bioavailable and stable. Utilizing proprietary SuperFluids(tm) technologies, we propose to encapsulate ?9-THC in biodegradable polymer nanospheres that will allow transport to the stomach, improve its stability and enhance bioavailability. ? ? In Phase II, we will carry out pharmacological, toxicological and pharmacokinetic evaluations of the developed formulation(s). We will also provide a GMP scale-up of a stable dosage form with acceptable in vitro and in vivo bioavailability in animal models and/or in humans. ? ? Narrative: The developed controlled release, oral formulation of ?9-THC will be commercialized for treating marijuana dependence and withdrawal symptoms, cancer pain, nausea associated with cancer chemotherapy and AIDS cachexia or wasting. ? ? ?
