The Research

Research Partnership

Research Base

In-House Case Studies

Spread the Word

Research Partnership

Over an 18 month period (via NIH research, an over-the-counter pilot program and ongoing case studies) Pebble developed a hypothesis and proprietary multi-cannabinoid & terpene formulation (well beyond CBD alone) focused specifically on severe neurological disorders and Cancer.
Pebble began a collaboration in Spring of ’20 with Dr. Anil Sood of the MD Anderson Cancer Center to test Pebble’s formulation for direct anti-tumor activity and to gather the data necessary for a State of Texas “CPRIT” grant to complete FDA Drug Development as a prescription adjuvant for cancer patients.
The proof of concept pre-clinical studies went well. In Nov. ’20, results of in vitro studies have been obtained in a screening study of 10 different ovarian cancer cell lines, with several showing equal or significantly more potency than with CBD alone.
The next step began January ’21 and it includes in vitro combination studies with standard of care chemotherapeutics in drug sensitive and resistant ovarian cancer cell lines. Proof of principle will then be confirmed in mouse models to assess anti-tumor efficacy and safety. Those results are expected in May/June of ’21, pandemic or other delays notwithstanding, and will form the basis of the CPRIT grant funding for human trials.

Pebble Research Base

CBD in various cancer types and mechanism:

Figure 3. In vitro-in vivoanticancer mechanism of CBD in different types of cancer and the related effects on proliferation/apoptosis/gene expression/oxidative stress/tumor growth [76-199]

Kis, B., Ifrim, F. C., Buda, V., Avram, S., Pavel, I. Z., Antal, D., Paunescu, V., Dehelean, C. A., Ardelean, F., Diaconeasa, Z., Soica, C., & Danciu, C. (2019). Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer. International journal of molecular sciences, 20(23), 5905. https://doi.org/10.3390/ijms20235905

CBD anti-tumor effects single agent

  1. Roberto D, Klotz LH, Venkateswaran V.  Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner. Prostate. 2019 Feb;79(2):151-159. doi: 10.1002/pros.23720. Epub 2018 Sep 21.
  2. Khan MI, Sobocińska AA, Brodaczewska KK, Zielniok K, Gajewska M, Kieda C, Czarnecka AM, Szczylik C. 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. BMC Cancer. 2018 May 23;18(1):583. doi: 10.1186/s12885-018-4496-1.
  3. Fonseca BM, Correia-da-Silva G, Teixeira NA. Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis. J Physiol Biochem. 2018 May;74(2):261-272. doi: 10.1007/s13105-018-0611-7. Epub 2018 Feb 13.
  4. Sreevalsan S, Joseph S, Jutooru I, Chadalapaka G, Safe SH. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent. Anticancer Res. 2011 Nov;31(11):3799-807
  5. Leelawat S, Leelawat K, Narong S, Matangkasombut O. The dual effects of delta(9)-tetrahydrocannabinol on cholangiocarcinoma cells: anti-invasion activity at low concentration and apoptosis induction at high concentration. Cancer Invest. 2010 May;28(4):357-63.
  6. Elbaz M, Nasser MW, Ravi J, Wani NA, Ahirwar DK, Zhao H, Oghumu S, Satoskar AR, Shilo K, Carson WE 3rd, Ganju RK (2015) Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: novel anti-tumor mechanism
  7. Cioni C, Tassi M, Marotta G, Mugnaini C, Corelli F, Annunziata P. A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in vitro Growth and TGF-beta Release of Human Glial Cell Tumors. Cent Nerv Syst Agents Med Chem. 2019;19(3):206-214. doi: 10.2174/1871524919666190923154351. high TGF beta levels prevent checkpoint inhibitor action anti-PDL1
  8. Dhital S, Stokes JV, Park N, Seo KS, Kaplan BL. Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation. Cell Immunol. 2017 Feb;312:25-34. doi: 10.1016/j.cellimm.2016.11.006. Epub 2016 Nov 9.

CBD in combination with chemotherapeutics

  1. Fraguas-Sánchez AI, Fernández-Carballido A, Simancas-Herbada R, Martin-Sabroso C, Torres-Suárez AI. CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer. Int J Pharm. 2020 Jan 25;574:118916. doi: 10.1016/j.ijpharm.2019.118916. Epub 2019 Dec 4.
  2. Ferro R, Adamska A, Lattanzio R, Mavrommati I, Edling CE, Arifin SA, Fyffe CA, Sala G, Sacchetto L, Chiorino G, De Laurenzi V, Piantelli M, Sansom OJ, Maffucci T, Falasca M. GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine. Oncogene. 2018 Dec;37(49):6368-6382. doi: 10.1038/s41388-018-0390-1. Epub 2018 Jul 30.
  3. Donadelli M, Dando I, Zaniboni T, Costanzo C, Dalla Pozza E, Scupoli MT, Scarpa A, Zappavigna S, Marra M, Abbruzzese A, Bifulco M, Caraglia M, Palmieri M. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis. 2011 Apr 28;2:e152. doi: 10.1038/cddis.2011.36.

CBD prevents side effects from chemotherapy (neuropathy, nephrotoxicity, cardiotoxicity)

  1. Deng L, Guindon J, Cornett BL, Makriyannis A, Mackie K, Hohmann AG. Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal. Biol Psychiatry. 2015 Mar 1;77(5):475-87. doi: 10.1016/j.biopsych.2014.04.009. Epub 2014 Apr 25.
  2. Pan H, Mukhopadhyay P, Rajesh M, Patel V, Mukhopadhyay B, Gao B, Haskó G, Pacher P. Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. J Pharmacol Exp Ther. 2009 Mar;328(3):708-14. doi: 10.1124/jpet.108.147181. Epub 2008 Dec 12.
  3. Hao E, Mukhopadhyay P, Cao Z, Erdélyi K, Holovac E, Liaudet L, Lee WS, Haskó G, Mechoulam R, Pacher P. Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis. Mol Med. 2015 Jan 6;21:38-45. doi: 10.2119/molmed.2014.00261.

CBD Case Studies

  1. Likar R1, Koestenberger M1, Stultschnig M2, Nahler G Concomitant Treatment of Malignant Brain Tumours With CBD – A Case Series and Review of the Literature. Anticancer Res. 2019 Oct;39(10):5797-5801. doi: 10.21873/anticanres.13783.
  2. Barrie, Allison M et al. “Dramatic response to Laetrile and cannabidiol (CBD) oil in a patient with metastatic low grade serous ovarian carcinoma.” Gynecologic oncology reports vol. 29 10-12. 17 May. 2019, doi:10.1016/j.gore.2019.05.004

In-House Case Studies

Pebble People have completed in-house case studies ranging from three to six months. Use the buttons below to view samples of the weekly reporting. Summaries and complete data sets are available upon request.

Please Spread the Word

Pebble’s growth depends on word of mouth from successful Pebble People. We need to gather as much data as possible.

Please refer anyone who is battling any of these these neurological disorders. Please also refer folks dealing with these cancers, taking these chemotherapy drugs, or experiencing any of these chemo side effects.

To show our gratitude, we’ll repeat your most recent order for free, no matter how big it was. Pebble will also automatically setup the person you refer (as an already diagnosed medical patient) with a permanent 40% off personal discount code.

Neurological

  • CDKL5

  • Autism Spectrum Disorder

  • Epilepsy

  • Multiple Sclerosis

  • Parkinson’s Disease

  • Essential Tremors

  • Inflammatory Pain

  • Bipolar Disorder

  • Post-Traumatic Stress Disorder

  • Anxiety

  • Depression

  • Other Neurological Conditions

Cancer

  • Brain

  • Breast

  • Cholangiocarcinoma (bile duct)

  • Colon

  • Colorectal

  • Endometrial

  • Gliomal/Glioblastoma (malignant tumor affecting the brain or spine)

  • Leukemia

  • Lung

  • Ovarian

  • Prostate

  • Renal

  • Uterine

Chemotherapy Drugs

  • Carboplatin (ovarian)

  • Cisplatin (treats multiple Cancers)

  • Cytarabine (leukemia)

  • Doxorubicin (treats bladder, breast, lung, stomach, ovarian, Hodgkin’s & non-Hodgkins lymphoma and certain types of leukemia)

  • Gemcitabine (pancreatic)

  • Paclitaxel (breast)

  • Vincristine (leukemia)

Chemo Side Effects

  • Inflammatory Pain

  • Neuropathy

  • Nephrotoxicity

  • Cardiotoxicity

At this time, Pebble does not claim to treat cancer or neurological disorders. The information provided on this site is for self-sufficient adult patients and caregivers. We have provided what the current valid research says about specific cannabinoid isolates and their potential with targeted indications. We have shared Pebble’s proprietary formula that combines those individually-researched cannabinoids with other proven plant-based anti-inflammatories in specific ratios, using guidelines on dosing and dose scheduling, in a focused effort to create a synergistic effect greater than the most beneficiary isolates. Please review in detail and make your own decision.