Profiling Cannabis spp. anti-tumor effects in cancer

Cannabinoid compounds and its analogs are known to have palliative effects in oncology, including: inhibition of nausea and emesis associated with chemotherapy, appetite stimulation, pain relief, mood elevation and relief from insomnia in cancer patients. In the last decade, accumulating evidence indicates that cannabinoids might also have antitumor effects as several studies demonstrated the use of cannabinoids in being able to regress different cancer types, such as glioma, breast cancer and skin carcinoma. These effects were further investigated in vitro, in various cancer cell lines, and revealed pro-apoptotic and anti-proliferative responses to cannabinoids, as well as inhibition of invasion and migration. However, the medical use of Cannabis remains limited due to the large number of active compounds that, together with variability among different Cannabis strains and cultivation methods, impairs our ability to predict the specific clinical effects and determine recommended dosages. In addition, the molecular mechanisms of action of cannabinoids are unknown and have yet to be investigated.

The main objective of our work is to identify how different Cannabis extracts affect various cancer types and to elucidate the mechanisms of cannabinoid-mediated antitumor effects. The results of this research could be instrumental in predicting how to match a cancer subtype with an effective Cannabis extract in order to optimize the treatment efficacy.

To demonstrate differential antitumor effects of different Cannabis extracts, we established a method for screening antitumor effects of cannabinoid compounds on various cancer subtypes in vitro. We work to identify the effects of different Cannabis extracts on proliferation and cell death of various cancer cell lines and we intend to classify these effects according to cell line genetic profiles. This enables us to detect the most effective Cannabis extract and cannabinoid profile for a certain cancer subtype. These results rely on our novel ability to analyze the chemical content and metabolomics of the Cannabis plants.

Our preliminary data shows that several Cannabis extracts are very potent in killing tumor cells. We found that different strains (each with a distinct cannabinoid composition) have differing yet deleterious effects on various tumor cell lines. The most potent, anti-proliferative, and/or pro-apoptotic Cannabis extracts to matched cell lines will be used as models to further elucidate the Cannabis components’ mechanisms of action. Our lab group recently discovered two new pathways that have been activated by Cannabis extracts in cancer cells and this work is a major research interest in our lab.

To strengthen our results, we are using xenograft mouse models to examine the potency of the Cannabis extracts and cannabinoid combinations. Moreover, we are collaborating with Professor Izhak Haviv, a senior professor specializing in personalized cancer medicine and diagnostic genomics. Together we can verify in vitro results of Cannabis extracts or cannabinoids combinations on patient-specific living cancer tissue, grown in xenograft mouse models. We are also collaborating with major Israeli hospitals and are participating in two clinical trials in the field of cancer and Cannabis.