Cannabics Pharmaceuticals

Healthcare Professionals

Pre-Clinical Studies

In our state of the art drug screening lab we are examining a library of cannabinoids and their effect on several types of cancers, aiming to develop a proprietary treatment for different cancer types.


The research is comprised of a set of essays that  have been  designed  to produce  a  comprehensive data  set  that can be used as basis for future anti-cancer clinical studies. Our preliminary results suggest that different THC / CBD ratios show differential effects on different cancer types.

Cannabics SR 5mg for Cancer Anorexia Cachexia Syndrome – CACS

Our clinical study was led by Professor Gil Bar-Sela, the Deputy Director of the Division of Oncology at Rambam Health Care Campus, Head of the Palliative and Supportive Oncology Unit, and Head of the service for Melanoma and Sarcoma Patients. The main endpoints of the treatment of patients with advanced cancer and CACS are weight gain and quality of life (QoL). The study is fully registered with the US NIH under “Cannabics Capsules as Treatment to Improve Cancer Related CACS in Advanced Cancer Patients”, Identifier NCT02359123, and may be found at https://clinicaltrials.gov/ct2/show/NCT02359123

Diagnostics

According to Grand View Research, Inc., the global cancer diagnostics market size was valued at USD 124.0 billion in 2016 and is expected to grow at an annual rate of over 7%. This market is expected to reach USD 232.7 billion by 2025 according to Orbis Research.

The growth in cancer cases, growing demand for effective diagnostic tools that develop from rising awareness, government support and technological developments are driving the demand for this increase worldwide.

Cancer is one of the leading causes of deaths worldwide which leads to efforts to develop accurate diagnostic tools and effective treatment solutions. Early monitoring and pre-detection are being focused on as this leads to improved success rate in treatment. This leads to public awareness and healthcare support programs that promote routine check-ups which enable diagnosing the disease before first symptoms may appear.

Palliative Care

Cannabis has long been suggested to stimulate appetite, decrease nausea and vomiting, and improve quality of life in cancer patients. Studies on the efficacy of cannabis for improving CACS and S-NIS have had mixed results. After trials showing improvement in weight gain among AIDS patients, cannabinoids were tested on cancer patients as well. In a controlled, random study comparing dronabinol to a placebo among cancer patients, dronabinol was associated with increased appetite in 38% vs 8% for placebo, and decreased nausea in 20% vs 7%, using acceptable measurement scales. Of the dronabinol patients, 22% gained ≥2 kg, compared with 10.5% of placebo recipients, but this datum did not reach significance, perhaps due to the advanced stage of cancer and the high mortality in both placebo and experimental group.

Another randomized study compared dronabinol to megestrol acetate or both treatments together. The research included 469 advanced cancer patients who had been suffering from a substantial appetite loss. A greater percentage of megestrol acetate-treated patients reported appetite improvement compared with dronabinol-treated patients, 75% vs 49% (p=0.0001). Combination treatment resulted in no significant differences compared with megestrol acetate alone. Another study, which included 243 patients, compared the administration of a combination of tetrahydrocannabinol and cannabinol to tetrahydrocannabinol alone, compared to placebo. It should be noted that cannabinoid dosages in the study were low, even in comparison to other studies. No significant differences between the groups were seen regarding improvement in appetite or weight-gain. In these two studies, no substantial side effects of cannabis products were found compared to the other arms. This may be related to the dosages of the drugs given.

A more recent study demonstrated improved chemosensory perception, appetite, sleep, and macronutrient preference in advanced cancer patients. However, the study included less than 50 patients. This research showed improvement in taste and smell perception in patients receiving chemotherapy, as well as appetite and caloric intake in the arm that received dronabinol compared to placebo.

Cannabinoid Compounds

Natural products have served as vital resources for cancer therapy (e.g.,Vinca alkaloids, paclitaxel, etc., which are used as conventional chemotherapeutic agents) and are also sources for novel drugs. Natural products from plants therefore represent an excellent resource for targeted therapies, as phytochemicals and herbal mixtures act multi-specifically, i.e. they attack multiple targets at the same time. Furthermore, the problem of drug resistance may be approached by integrating phytochemicals and phyto-therapy into academic western medicine through derivation and integration of data and as adjunct to conventional treatments. The integration of phytochemicals and phyto-therapy into cancer medicine represents a valuable asset to chemically synthesized chemicals and therapeutic antibodies. Cannabinoids are excellent candidates for this approach. Cannabinoids are a class of over 60 compounds derived from the plant cannabis sativa, as well as the synthetic or endogenous versions of these compounds. Cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. These effects are exerted through cannabinoid receptors CB1 and CB2 in mammals and through non-receptor signaling pathways. Recent studies suggest that cannabinoids contribute to maintaining balance in cell proliferation and that targeting the endo-cannabinoid system can affect growth of several different types of cancer, including gliomas, breast, colon, prostate, and hepatocellular carcinoma.

Publications

Cannabis kills tumor cells

1. Cannabinoids in Glioblastoma Therapy: New Applications for Old Drugs.

Dumitru CA, Sandalcioglu IE, Karsak M.Front Mol Neurosci. 2018 May 16;11:159.

2. The current state and future perspectives of cannabinoids in cancer biology.2018. Cancer Medicine.
Paweł Śledziński , Joanna Zeyland, Ryszard Słomski& Agnieszka Nowak. Cancer Medicine 2018; 7(3):765–775.

3. Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents

Daniel A. Ladin, Eman Soliman, LaToya Griffin and Rukiyah Van Dross
Front. Pharmacol., 07 October 2016.

4. The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.

Carracedo A, Lorente M, Egia A, Blázquez C, García S, Giroux V, Malicet C, Villuendas R, Gironella M, González-Feria L, Piris MA, Iovanna JL, Guzmán M, Velasco G.Cancer Cell. 2006 Apr;9(4):301-12.

5. The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway.

Herrera B1, Carracedo A, Diez-Zaera M, Gómez del Pulgar T, Guzmán M, Velasco G. Exp Cell Res. 2006 Jul 1;312(11):2121-31. Epub 2006 Apr 19.

6. Involvement of cannabinoids in cellular proliferation.

López-Rodríguez ML, Viso A, Ortega-Gutiérrez S, Díaz-Laviada I.
Mini Rev Med Chem. 2005 Jan;5(1):97-106.

7. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor.

Hart S, Fischer OM, Ullrich A. Cancer Res. 2004 Mar 15;64(6):1943-50.

8. Cannabinoid receptor systems: therapeutic targets for tumor intervention.
Jones S, Howl J. Expert Opin The Targets. 2003 Dec;7(6):749-58.

9. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation.

Galve-Roperh I, Sánchez C, Cortés ML, Gómez del Pulgar T, Izquierdo M, Guzmán M.Nat Med. 2000 Mar;6(3):313-9.

Uterine, testicular, and pancreatic cancers

10. Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212-2 in renal cell carcinoma.

Mohammed I. Khan Anna A. Sobocińska, Klaudia K. Brodaczewska , Katarzyna Zielniok , Malgorzata Gajewska , Claudine Kieda , Anna M. Czarnecka and Cezary Szczylik. BMC Cancer (2018) 18:583.

11. GPR55 signaling promotes proliferation of pancreatic cancer cells and tumor growth in mice, and its inhibition increases effects of gemcitabine. Oncogen.2018.

R. Ferro, A. Adamska, R. Lattanzio, I. Mavrommati, C. E. Edling, S. A. Arifin, C. A. Fyffe, G. Sala, L. Sacchetto, G. Chiorino, V. De Laurenzi, M. Piantelli, O. J. Sansom, T. Maffucci, M. Falasca. Oncogene, 2018; DOI: 10.1038/s41388-018-0390-1.

12. Cannabis-derived substances in cancer therapy–an emerging anti-inflammatory role for the cannabinoids.

Liu WM1, Fowler DW, Dalgleish AG.Curr Clin Pharmacol. 2010 Nov;5(4):281-7.

13. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes.

Carracedo A1, Gironella M, Lorente M, Garcia S, Guzmán M, Velasco G, Iovanna JL.Cancer Res. 2006 Jul 1;66(13):6748-55.

Brain cancer.

14. The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas.

Eiron Cudaback , William Marrs, Thomas Moeller , Nephi Stella.Plos one January 14, 2010.

15. Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas.

De Jesús ML1, Hostalot C, Garibi JM, Sallés J, Meana JJ, Callado LF. Neurochem Int. 2010 May-Jun;56(6-7):829-33. doi: 10.1016/j.neuint.2010.03.007. Epub 2010 Mar 20.

16. Predominant CB2 receptor expression in endothelial cells of glioblastoma in humans
Schley M, Ständer S, Kerner J, Vajkoczy P, Schüpfer G, Dusch M, Schmelz M, Konrad C.Brain Res Bull. 2009 Jun 30;79(5):333-7. doi: 10.1016/j.brainresbull.2009.01.011. Epub 2009 Feb 6.

17. Cannabis use and cancer of the head and neck: Case-control study

Sarah Aldington,a Matire Harwood,a Brian Cox,b Mark Weatherall,c Lutz Beckert,a Anna Hansell,d Alison Pritchard,aGeoffrey Robinson, Richard Beasley,a,e,⁎ and Cannabis and Respiratory Disease Research Group. Otolaryngol Head Neck Surg. 2008 Mar; 138(3): 374–380.

18. Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells.

Galanti G1, Fisher T, Kventsel I, Shoham J, Gallily R, Mechoulam R, Lavie G, Amariglio N, Rechavi G, Toren A. Acta Oncol. 2008;47(6):1062-70

19. Cannabinoids and gliomas.

Velasco G, Carracedo A, Blázquez C, Lorente M, Aguado T, Haro A, Sánchez C, Galve-Roperh I, Guzmán M.Mol Neurobiol. 2007 Aug;36(1):60-7. Epub 2007 Jun 28.

20. Cannabinoid receptors in human astroglial tumors.

Held-Feindt J1, Dörner L, Sahan G, Mehdorn HM, Mentlein R.J Neurochem. 2006 Aug;98(3):886-93.

21. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism.
Vaccani A, Massi P, Colombo A, Rubino T, Parolaro D. British Journal of Pharmacology. 2005;144(8):1032-1036.

22. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor‐independent mechanism

Angelo Vaccani, Paola Massi, Arianna Colombo, Tiziana Rubino, Daniela Parolaro.British Journal of Pharmacology (2005) 144, 1032–1036.

23. Hypothesis: cannabinoid therapy for the treatment of gliomas?

Velasco G, Galve-Roperh I, Sánchez C, Blázquez C, Neuropharmacology. 2004 Sep;47(3):315-23.

Breast cancer

24. Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer.

Blasco-Benito S, Seijo-Vila M, Caro-Villalobos M, Tundidor I, Andradas C, García-Taboada E, Wade J, Smith S, Guzmán M, Pérez-Gómez E, Gordon M, Sánchez C. Send to Biochem Pharmacol. 2018 Jun 27.

25. Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.

Fraguas-Sánchez AI, Fernández-Carballido A, Torres-Suárez AI.
Expert Opin Investig Drugs. 2016 Nov;25(11):1311-1323. Epub 2016 Sep 28.

26. Cannabinoids may be therapeutic in breast cancer.

Behrend SW. Send to Oncol Nurs Forum. 2013 Mar;40(2):191-2.

27. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

McAllister, Rigel T. Christian, Maxx P. Horowitz, Amaia Garcia and Pierre-Yves Desprez. MCT-07-0371 Published November 2007

Lung cancer

28. Enhancing the Therapeutic Efficacy of Cancer Treatment with Cannabinoids.

Yasmin-Karim S, , Moreau M, Mueller R, Sinha N, Dabney R, Herman A, Ngwa W. Front Oncol. 2018 Apr 24;8:114.

29. Cannabinoid receptor-2 agonist inhibits macrophage induced EMT in non-small cell lung cancerby downregulation of EGFR pathway.

Ravi J, Elbaz M, Wani N Mol Carcinog. 2016 Dec;55(12):2063-2076.

30. Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

Haustein M, Ramer R, Linnebacher M, Manda K, Hinz B. Biochem Pharmacol. 2014 Nov 15;92(2):312-25.

31. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1.

Ramer R, Bublitz K, Freimuth N, Merkord J, Rohde H, Haustein M, Borchert P, Schmuhl E, Linnebacher M, Hinz B. FASEB J. 2012 Apr;26(4):1535-48.

32. Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis.

Preet A, Qamri Z, Nasser MW, Prasad A, Shilo K, Zou X, Groopman JE, Ganju RK. Cancer Prev Res (Phila). 2011 Jan;4(1):65-75.

Blood cancer

33. Anti-Proliferative Properties and Proapoptotic Function of New CB2 Selective Cannabinoid Receptor Agonist in Jurkat Leukemia Cells.

Capozzi A, Mattei V, Martellucci S, Manganelli V, Saccomanni G, Garofalo T, Sorice M, Manera C, Misasi R. Int J Mol Sci. 2018 Jul 4;19(7).

34. Anticancer effects of phytocannabinoids used with chemotherapy in leukemia cells can be improved by altering the sequence of their administration.2017. International Journal of Oncology.

Katherine A. Scott Angus G. Dalgleish Wai M. Liu. Journal of Oncology May 29, 2017.

35. Delta9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria.

Jia W, Hegde VL, Singh NP, Sisco D, Grant S, Nagarkatti M, Nagarkatti PS.Mol Cancer Res. 2006 Aug;4(8):549-62.

36. Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells.

Gallily R, Even-Chena T, Katzavian G, Lehmann D, Dagan A, Mechoulam R.
Leuk Lymphoma. 2003 Oct;44(10):1767-73.

37. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease.

McKallip RJ, Lombard C, Fisher M, Martin BR, Ryu S, Grant S, Nagarkatti PS, Nagarkatti M.Blood. 2002 Jul 15;100(2):627-34.

Skin cancer

38. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors.

Casanova ML, Blázquez C, Martínez-Palacio J, Villanueva C, Fernández-Aceñero MJ, Huffman JW, Jorcano JL, Guzmán M. J Clin Invest. 2003 Jan;111(1):43-50.

39. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities.

ró T, Tóth BI, Haskó G, Paus R, Pacher P. Trends Pharmacol Sci. 2009 Aug;30(8):411-20.

40. Anandamide-induced endoplasmic reticulum stress and apoptosis are mediated by oxidative stress in non-melanoma skin cancer: Receptor-independent endocannabinoid signaling.

Soliman E, Van Dross R. Mol Carcinog. 2016 Nov;55(11):1807-1821.

41. The role of cannabinoids in dermatology.

Mounessa JS, Siegel JA, Dunnick CA, Dellavalle RP. J Am Acad Dermatol. 2017 Jul;77(1):188-190.

42. Cannabinoid receptors as novel targets for the treatment of melanoma.
Blázquez C, Carracedo A, Barrado L, Real PJ, Fernández-Luna JL, Velasco G, Malumbres M, Guzmán M. FASEB J. 2006 Dec;20(14):2633-5. Epub 2006 Oct 25.

liver and colon cancer

43. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy.

Vara D, Salazar M, Olea-Herrero N, Guzmán M, Velasco G, Díaz-Laviada I. Cell Death Differ. 2011 Jul;18(7):1099-111.

44. Estrogenic induction of cannabinoid CB1 receptor in human colon cancer cell lines.

Notarnicola M, Messa C, Orlando A, Bifulco M, Laezza C, Gazzerro P, Caruso MG. Scand J Gastroenterol. 2008 Jan;43(1):66-72.

45. Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de novo synthesis in colon cancer cells.

Cianchi F, Papucci L, Schiavone N, Lulli M, Magnelli L, Vinci MC, Messerini L, Manera C, Ronconi E, Romagnani P, Donnini M, Perigli G, Trallori G, Tanganelli E, Capaccioli S, Masini E. Clin Cancer Res. 2008 Dec 1;14(23):7691-700.