| Preventing cognitive impairment by using intranasal delivery of Cannabinoids for high risk populations

Yakir Rottenberg M.D.

Cannabinoids have attracted interest in Alzheimer disease given their benefits in reducing classic neurotoxic events in the disease, such as excessive glutamatergic transmission, prolonged calcium influx, oxidative stress, and inflammation. Indeed, greater concentrations of CBD have been associated with increased gray matter in the hippocampus which is negative correlate with cognitive decline. Furthermore, they were successfully investigated in preclinical models (e.g., 5×FAD, PS1/APP+ mice).
Administration of CBD relies heavily on inhalation or the ingestion of solutions or capsules. CBD first moved into the bloodstream and then pass through the liver followed by metabolize process. Consequently, effective prevention efficacy is hampered by unpredictable and inconsistent process.
Intranasal olfactory administration represents the only direct access to the brain that can be used for non-invasive delivery of agents. Using this route of drug delivery requires nanoparticles of a certain size and surface properties as well as fast elimination of the carrier for safe and effective drug administration in the brain. A mice model for Thyrotropin-releasing hormone (TRH) delivery provides proof of this principle. TRH stimulates the release of TRH and has an anticonvulsant effect. Successful delivery of a TRH has been reported by our team in sufficient concentrations to suppressed seizures. We propose the use of the fast degrading poly(Sebacic Anhydride) (PSA) and lipid carriers for nanoparticles olfactory delivery carriers of CBD in order to enhance the potential efficacy for prevention of cognitive impairment.