Abstract In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called ‘endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based...

Therapeutic options for amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, remain limited. Emerging evidence from clinical studies and transgenic mouse models of ALS suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. However, D9 -tetrahydrocannabinol (D9 -THC), the predominant cannabinoid in marijuana, induces mind-altering effects and is partially addictive, compromising its clinical usefulness. We therefore tested whether cannabinol (CBN), a nonpsychotropic cannabinoid, influences disease progression and survival in the SOD1 (G93A) mouse model of ALS. CBN was delivered via subcutaneously implanted osmotic mini-pumps (5 mg/kg/day) over a period of up to...

The endocannabinoid signaling system is composed of the cannabinoid receptors; their endogenous ligands, the endocannabinoids; the enzymes that produce and inactivate the endocannabinoids; and the endocannabinoid transporters. The endocannabinoids are a new family of lipidic signal mediators, which includes amides, esters, and ethers of long-chain polyunsaturated fatty acids. Endocannabinoids signal through the same cell surface receptors that are targeted by 9 -tetrahydrocannabinol (9 -THC), the active principles of cannabis sativa preparations like hashish and marijuana. The biosynthetic pathways for the synthesis and release of endocannabinoids are still rather uncertain. Unlike neurotransmitter molecules that are typically held in vesicles before synaptic release, endocannabinoids are synthesized...

OBJECTIVE: To test in vitro and in vivo the safety and efficacy of a novel chemotherapeutic agent, KM-233, for the treatment of glioma. METHODS: In vitro cell cytotoxicity assays were used to measure and compare the cytotoxic effects of KM-233, Delta(8)-tetrahydrocannabinol (THC), and bis-chloroethyl-nitrosurea (BCNU) against human U87 glioma cells. An organotypic brain slice culture model was used for safety and toxicity studies. A human glioma-SCID mouse side-pocket tumor model was used to test in vivo the safety and efficacy of KM-233 with intratumoral and intra-peritoneal administration. RESULTS: KM-233 is a classical cannabinoid with good blood brain barrier penetration that possesses a selective affinity...