Synergistic Effect Of Cannabidiol With Conventional Chemotherapy Treatment

Diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) represent the most common and most aggressive forms of Non-Hodgkin lymphoma (NHL) respectively. Traditional chemotherapy includes (C)yclophosphamide, (H)ydroxydaunorubicin, (O)ncovin (vincristine) and (P)rednisone or (P)rednisolone (CHOP); or (R)ituximab-CHOP. However, in the past 10 years, other more targeted drugs have been developed for treatment of NHLs that includes Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib (IBN) and proteasome inhibitors such as carfilzomib (CFZ). Presently, there is a high interest in the endocannabinoid system, with specific interest in CB1 and CB2 ligands as potential therapeutic targets for both DLBCL and MCL. Cannabidiol (CBD) is a natural cannabinoid analog that has mixed affinity across CB1 and CB2 receptors; known in the literature as a CB1 antagonist and a CB2 agonist. Our previous work has demonstrated that CB1 antagonists has activity against DLBCL and MCL cell lines. Our study is aimed at comparing CBD against conventional chemotherapeutics, individually and in combination, in DLBCL and MCL cell lines. Here, we demonstrate that CBD in combination with known chemotherapeutics, ibrutinib (IBN), carfilzomib (CFZ), zanubrutinib (BGB) and tumorex (TMX), has synergistic potential in treating DLBCL and MCL cell lines.