CANNABIS AND CANCER. Case Presentations: Administering low-dose cannabis oil for the treatment of prostate cancer and brain cancer patients

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CANNABIS AND CANCER Case Presentations: Administering low-dose cannabis oil for the treatment of prostate cancer and brain cancer patients Debra Kimless, M.D. Medical Director, ForwardGro CannMed 2017 Harvard University April 2017

WHAT IS MICRO-DOSE? 1 joint =1gram=1000mg 20% THC=200mg 30%-40%=60mg-80mg Micro-Dose 1mg-2mg

TREATMENT

LIGRESTI ET AL 2006

PROSTATE CANCER: Two Patients

HISTORY 72 year-old male with the recurrent prostate cancer. 2011 Diagnosed Gleason score 8, Clinical state T2b, and PSA 7.2. Treatment: hormone deprivation, seed implant and 25 sessions of IMRT. Result: PSA level dropped to 0.3 and remained stable from 7/2011-11/2015. 11/2015 -PSA level began to rise to 1.0 8/2016 PSA level 7.8, Biopsy revealed recurrent cancer of the prostate, CT scan and bone scans negative for metastasis

TREATMENT BEGAN FIRST OF THREE LEUPROLIDE INJECTIONS PSA 7.8 STARTED LOW DOSE CANNABIS OIL CHANGED DIET CONTINUED SECOND AND THIRD LEUPROLIDE INJECTION

RESULTS

HISTORY 81year-old otherwise healthy man with one year history of metastatic prostate cancer. Treatment with seed implants, radiation therapy and leuprolide injections. Escalating testosterone levels Surgery to remove the testicles (orchiectomy)

RESULTS

STUDIES: Pacher, P. "Towards the Use of Non-Psychoactive Cannabinoids for Prostate Cancer". Brit. J. Pharmacology, 2013. 168(1):76-78. Diaz-Laviada, et al. "The Endocannabinoid System in Prostate Cancer". Nat. Rev. Urol. 2011. 8:553-561. Sreenvalsan, S. "Induction of Apoptosis by Cannabinoids in Prostate and Colon Cancer Cells is Phosphate Dependent". Anticancer Research, 2011 31(11) pp. 3799-3807.

BRAIN CANCER: Two Patients

HISTORY: 8 yo with Acute Lymphocytic Leukemia Failed MULTIPLE CHEMOTHERAPY AND RADIATION TRIALS Failed BONE MARROW TRANSPLANT HOSPICE

CHIEF COMPLAINTS: CHRONIC NAUSEA LACK OF APPETITE HEADACHE LACK OF ENERGY

EVALUATION: LETHARGIC NON-COMMUNICATIVE SWOLLEN

MEDICATIONS: METHADONE 10 mg/day MORPHINE 13.5 mg/day BOTH IN DIVIDED DOSES

MRI FEBRUARY 2015

GOALS: IMPROVE QUALITY OF LIFE IMPROVE PAIN TRANSITION OFF OPIOIDS

TREATMENT 1 ml oil SL four times a day

RESPONSE: INITIAL REDUCTION AND THEN REPLACEMENT OF ALL OPIOIDS MORE ACTIVE APPROPRIATE DEMEANOR

MRI APRIL 2015

COMPARISON

STUDIES: Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA Antineoplastice Activity of Cannabinoids J.National Cancer Inst. 1975 55(3): 597-602. Powles, T. et.al. Cannabis Induced Cytotoxicity in Leukemic Cell Lines; The Role of the Cannabinoid Receptors and the MAPK Pathway. Blood 105 (2005): 1214-1221. Herrera, R. et.al. The CB2 Cannabinoid Receptor Signals Apoptosis via Ceramide-Dependent Activation of the Mitochondrial Intrinsic Pathway Experimental Cell Research 312.11 (2006): 2121-2131. Jia, W. et.al. Delta-9-Tetrahydrocannabinol Apoptosis in Jurkat Leukemia T Cells is Regulated by Translocation of Bad to Mitochondria Molecular Cancer Research 4.8 (2006): 549-562. McKallip, R. et.al. Cannabidiol- Induced Apoptosis in Human leukemia Cells: A Novel Role of CBD in the Regulation of p22 phox and Nox4 Expression J. Molecular Pharmacology 70(3) (2006): 897-908.

ADDITIONAL STUDIES: Ligresti et al. Antitumor Activity of Plant Cannabinoids With Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma J Pharmacol Exp Ther. 2006;318:1375 1387. Liu, W. Enhancing the in-vitro Cytotoxic Activity of Delta-9- Tetrahydrocannabinol in Leukemic Cells Through a Combinatorial Approach Leukemia and Lymphoma 49(9) (2008): 1800-1809. Scott, Katherine Ann et al. Enhancing the Activity of Cannabidiol and other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules ANTICANCER RESEARCH 33: 4373-4380 (2013) Singh, Y. et.al. Cannabis Extract Treatment for Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation Case Reports in Oncology 6.3 (2013): 585-592.

HISTORY: Otherwise healthy 69 year old Presents to ER post-ictal MRI reveals a tumor Biopsy diagnosed glioblastoma

CHIEF COMPLAINT: Lethargy Inability to perform ADL s without assistance Cognitive changes

MEDICATIONS: Carbamazepine (Tegretol )

MRI PRE-TREATMENT

GOALS: Improve quality of life Improve function Reduce tumor growth

MRI TWO WEEKS LATER

COMPARISON:

STUDIES: Marcu JP et al: Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther 9: 180-189, 2010. María Salazar, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clinical Investigation 2009. Blazquez et.al. Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression. 68.6 (2008) 1945-52. Blazquez et.al. Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas Cancer Research 64.16 (2004) ; 5617-23. Massi et.al. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. The Journal of Pharmacology and Experimental Therapeutics 308.3 (2004) 838-845.

ADDITIONAL STUDIES: Solinas et.al. Cannabidiol, a nonpsychoactive cannabinoid compound, inhibits proliferation and invasion in U87-MG and T98G glioma cells through a multitarget effect. PLoS One 8.10 (2013): e76918. Vaccani et.al. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism British Journal of Pharmacology 144.8 (2005): 1032-1036.

UPDATE: 9 MONTHS LATER

Deb@ForwardGro.com