Compositions comprising cannabidiol and second therapeutic agents for the treatment of cancer

Abstract

The invention provides synergistic combinations of cannabidiol (CBD) and a second therapeutic agent, such as one or more ChEH/AEBS inhibitors, a naphthoquinone or a derivative thereof, or any combination thereof, effective for the treatment cancer. Compositions containing same and methods of use of same are described.

1 - 55 . (canceled) 
     
     
         56 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising:
 a synergistic combination of cannabidiol (CBD) and at least one cholesterol epoxide hydrolase/anti-estrogen binding site (ChEH/AEBS) inhibitor compound, wherein the ChEH/AEBS inhibitor compound is a selective estrogen receptor modulator (SERM); and   a pharmaceutically acceptable carrier.   
     
     
         57 . The method of  claim 56 , wherein the SERM comprises wherein the SERM comprises a cationic aminoethoxy side chain. 
     
     
         58 . The method of  claim 56 , wherein the cancer is cancer of the bile duct, cancer of the bladder, cancer of the bone, cancer of the bowel, cancer of the brain, cancer of the breast, cancer of the neuroendocrine system, cancer of the cervix, cancer of the eye, cancer of the esophagus, cancer of the head and neck, Kaposi's sarcoma, cancer of the kidney, cancer of the larynx, leukemia, acute leukemia, chronic lymphocytic leukemia, cancer of the liver, cancer of the lung, cancer of the lymph nodes, Hodgkin's lymphoma, non-Hodgkin's lymphoma, melanoma, mesothelioma, myeloma, cancer of the ovary, cancer of the pancreas, cancer of the penis, cancer of the prostate, skin cancer, soft tissue sarcomas, cancer of the spinal cord, cancer of the stomach, testicular cancer, cancer of the thyroid, cancer of the vagina, cancer of the vulva and cancer of the uterus. 
     
     
         59 . The method of  claim 56 , wherein the cancer is a blood or a bone marrow related cancer. 
     
     
         60 . The method of  claim 56 , wherein the cancer is glioblastoma. 
     
     
         61 . The method of  claim 56 , wherein the cancer is breast cancer. 
     
     
         62 . The method of  claim 56 , wherein the cancer is an estrogen receptor-negative cancer. 
     
     
         63 . The method of  claim 57 , wherein the SERM comprises clomiphene, tamoxifen, 4-hydroxy-tamoxifen, raloxifene or a combination thereof. 
     
     
         64 . The method of  claim 63 , wherein the SERM comprises clomiphene. 
     
     
         65 . The method of  claim 57 , wherein the SERM comprises a triphenylethylene (TPE) or a derivative thereof containing a cationic aminoethoxy side chain, or a combination thereof. 
     
     
         66 . A composition comprising a synergistic combination of cannabidiol (CBD) and at least one cholesterol epoxide hydrolase/anti-estrogen binding site (ChEH/AEBS) inhibitor compound, which ChEH/AEBS inhibitor compound is not a selective estrogen receptor modulator (SERM) and is a selective inhibitor of ChEH/AEBS, wherein the CBD is present in an amount sufficient to provide a dose of 0.1 mg/kg to 50 mg/kg to a subject and the ChEH/AEBS inhibitor compound is present in an amount sufficient to provide a dose of 500 mg/kg to 2000 mg/kg to the subject, and the selective inhibitor is 1-[2-[4-(phenylmethyl)phenoxy]ethyl]-Pyrrolidine (PBPE) or tesmilifene (DPPE). 
     
     
         67 . The composition of  claim 66 , wherein the selective inhibitor is DPPE. 
     
     
         68 . The composition of  claim 66 , further comprising a pharmaceutically acceptable carrier. 
     
     
         69 . An anti-cancer pharmaceutical composition which comprises the composition of  claim 68  in a therapeutically effective amount. 
     
     
         70 . A method of treating leukemia, breast cancer, or glioblastoma, which comprises administering to a subject in need thereof a therapeutically effective amount of the composition of  claim 68 . 
     
     
         71 . A method for treating a subject in need of leukemia, breast cancer, or glioblastoma therapy, which comprises administering to the subject a therapeutically effective amount of the composition of  claim 66  for the treatment of leukemia, breast cancer, or glioblastoma. 
     
     
         72 . The method of  claim 71 , wherein the selective inhibitor is DPPE. 
     
     
         73 . The method of  claim 71 , wherein the composition is administered intravenously, orally, or sublingually. 
     
     
         74 . The method of  claim 71 , wherein the composition is administered to the subject for a duration of between 24 hours to 14 days, or between 24 hours to 30 days. 
     
     
         75 . The composition of  claim 66 , wherein the ChEH/AEBS inhibitor comprises a cholesterol biosynthesis inhibitor. 
     
     
         76 . The composition of  claim 75 , wherein the cholesterol biosynthesis inhibitor comprises Triparanol, Teribinafine, U-18666 A, or a combination thereof. 
     
     
         77 . The composition of  claim 66 , wherein the ChEH/AEBS inhibitor comprises a ring B oxysterol. 
     
     
         78 . The composition of  claim 77 , wherein the ring B oxysterol comprises 6-ketocholestanol, 7-ketocholestanol, 7-ketocholesterol and Cholestane-3b,5a,6b-triol(CT) or combinations thereof. 
     
     
         79 . A composition comprising a synergistic combination of cannabidiol (CBD) and at least one naphthoquinone or a derivative thereof. 
     
     
         80 . The composition of  claim 79 , wherein the naphthoquinone or a derivative thereof comprises menadione.