No abstract

The therapeutic effect of the Cannabis plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. Although prescription of medicinal Cannabis 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 Cannabis 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 Cannabis 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 Cannabis delivery system may provide new form of Cannabis administration and treatments.

R Antitumoral effects of cannabis in Notch1-mutated T-cell acute lymphoblastic leukemiaDear Editor,In T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematologic cancer with poor clinical outcomes, more than 50% of cases show NOTCH1-driven transformation [1]. The NOTCH1 receptor signaling pathway is activated through a series of proteolytic cleavages, ultimately causing the release of the active intracellular domain (NICD), which translocates to the nucleus where it promotes transcription of target genes involved in cell growth. The importance of NOTCH1 mutations in T-ALL has generated great interest in the development of anti-NOTCH1 targeted therapies. A new and promising emerging field in cancer treatment is medical cannabis. Accumulating evidence suggests the direct effects of cannabis on tumor progression in cell lines and animal models [2]. Cannabis, and its unique secondary metabolites, known as phytocannabinoids, directly affect the propagation of cancer cells by modulating key cellsignaling pathways [3]. We have previously demonstrated that different cannabis extracts, each containing a unique composition of metabolites, selectively impaired the survival of cancer cell lines depending on a match between the chemical composition of the extract and the characteristics of the specific cancer cell line [4]. In the present work, we set out to investigate whether cannabis extracts with unique phytocannabinoid profiles can selectively facilitate antitumor effects in T-ALL cells that harbor a Notch1 mutation.We first performed a preliminary screening in which the viability of four distinct T-ALL cell lines was tested when