Full-Spectrum Extract Microdepots Support Controlled Release of Multiple Phytocannabinoids for Extended Therapeutic Effect.

The therapeutic effect of the plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. Although prescription of medicinal for various conditions constantly grows, its consumption is mostly limited to oral or respiratory pathways, impeding its duration of action, bioavailability, and efficacy. Herein, a long-acting formulation in the form of melt-printed polymeric microdepots for full-spectrum cannabidiol (CBD)-rich extract administration is described. When injected subcutaneously in mice, the microdepots facilitate sustained release of the encapsulated extract over a two-week period. The prolonged delivery results in elevated serum levels of multiple, major and minor, phytocannabinoids for over 14 days, compared to extract injection. A direct analysis of the microdepots retrieved from the injection site gives rise to an empirical model for the release kinetics of the phytocannabinoids as a function of their physical traits. As a proof of concept, we compare the long-term efficacy of a single administration of the microdepots to a single administration of extract in a pentylenetetrazol-induced convulsion model. One week following administration, the microdepots reduce the incidence of tonic-clonic seizures by 40%, increase the survival rate by 50%, and the latency to first tonic-clonic seizures by 170%. These results suggest that a long-term full-spectrum delivery system may provide new form of administration and treatments.