Article by Justin L Scharton, Independent Researcher
Article written on March 10, 2025
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Disclaimer: This information is provided for informational purposes only and is not intended to diagnose, treat, or cure any condition. Always consult a licensed medical professional before making changes to your healthcare regimen.
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Pancreatic Cancer - Targeting TRPM8 and GPR55 with CBD, THC, and Eucalyptol
Cannabinoids for pancreatic cancer: CBD + THC
Terpenes for pancreatic cancer: eucalyptol (1,8 cineole)
Target receptors: TRPM8 and GPR55 (93F,94F)
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TRPM8 receptors are upregulated in human pancreatic adenocarcinoma cell lines and tissues. Pancreatic cancer cells that are deficient in TRPM8 have a reduced ability to proliferate. (93F) Pancreatic ductal adenocarcinoma have their motility inhibited by the activation of TRPM8. (95F)
Those studies basically mean that TRPM8 receptors are upregulated in human pancreatic adenocarcinoma cell lines. In cancer types that have low amounts of TRPM8, they are less able to proliferate.
GPR55 is overexpressed in pancreatic cancer. Mice with that cancer were treated with CBD and gemcitabine lived three times longer compared to mice treated with the vehicle (placebo) or gemcitabine alone. Inhibiting GPR55 reduced anchorage dependent and independent growth, cell cycle progression, activated mitogen-activated protein kinase (MAPK) signaling and protein levels of ribonucleotide reductases. (94F)
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CBD for pancreatic cancer
Most pancreatic cancers overexpress TRPM8 and GPR55 receptors. (93F,94F) TRPM8 inhibitors are bad for this cancer, while GPR55 antagonists are beneficial. CBD is an antagonist of TRPM8 and GPR55, and was already studied to be a benefit to pancreatic cancer. (94F) Even though CBD is an antagonist of TRPM8, they affect many other receptors which could modulate its effect on the cancer cells directly or through enhancing the immune cells with activating those receptors. The study using a TRPM8 inhibitor used N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride salt which will act differently than CBD.
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Eucalyptol for pancreatic cancer
Eucalyptol (1.8 cineole) is a TRPM8 agonist, (33D) which would be the most beneficial terpene based on the pharmacological targets available that is treatable with cannabinoids and terpenes. This terpene can have side effects including lowering blood sugar, (35D) which should be used cautiously. Small frequent doses would be better tolerated than large doses.
Warning: TRPM8 activation (such as with eucalyptol) can create a cold sensation and influence blood pressure. People with certain heart conditions or disorders like Raynaud’s Disease, where cold worsens or trigger symptoms should use caution if they decide to try it, ask for medical advice, or not use it at all.
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Low blood sugar warning with CBD, THC, and eucalyptol
CBD and Delta 9 THC activate PPARy (PPAR-gamma).10B Activation of PPARy is known for causing insulin sensitization and enhances glucose metabolism. (11B) CBD can make the low blood sugar worse from activating PPARy, especially when combined with eucalyptol.
Low blood sugar symptoms include feeling shaky or jittery, hungry, tired, dizzy, lightheaded, confused, irritable, headache, heart beating too fast or not steadily, or having a hard time speaking clearly. (39D)
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Will THC help with pancreatic cancer
THC has not been researched for pancreatic cancer. THC will interact with the immune cells, increasing their own anti-cancer function.
THC will activate TRPV2 receptors on granulocytes, macrophages, monocytes, CD4+ and CD8+ T-lymphocytes, CD19+ B-lymphocytes, and CD56+ Natural Killer cells. (35A) Pancreatic cancer patients are often deficient in properly functioning CD4, CD8 T cells, and dendritic cells. (96F)
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Cannabinoids that activate T cells, and dendritic cells
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T-cells: CB1, CB2, TRPA1, TRPV2, TRPM8 (35A,77A,80A,94E,95E)
Dendritic Cells: CB1, CB2, TRPA1, TRPV1, TRPV2 (35A,77A,78A,80A,92E)
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THC activates GPR55
Delta 9 THC activates GPR55, while CBD inhibits GPR55. (86A) THC could be helpful with pancreatic cancer since it is an agonist of GPR55. This needs to be researched, but a combination of CBD, THC, and eucalyptol could be the best combination for pancreatic cancer.
See breast cancer section for cannabinoid dosing.
Sources
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35A. Santoni G, Farfariello V, Liberati S, Morelli MB, Nabissi M, Santoni M, Amantini C. The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses. Front Immunol. 2013 Feb 14;4:34. doi: 10.3389/fimmu.2013.00034. PMID: 23420671; PMCID: PMC3572502.
77A. Kaplan BL. The role of CB1 in immune modulation by cannabinoids. Pharmacol Ther. 2013 Mar;137(3):365-74. doi: 10.1016/j.pharmthera.2012.12.004. Epub 2012 Dec 20. PMID: 23261520.
78A. Aristizábal B, González Á. Innate immune system. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors. Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press; 2013 Jul 18. Chapter 2. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459455/
80A. Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 1995 Aug 15;232(1):54-61. doi: 10.1111/j.1432-1033.1995.tb20780.x. PMID: 7556170.
86A. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008 Jan;153(2):199-215. doi: 10.1038/sj.bjp.0707442. Epub 2007 Sep 10. PMID: 17828291; PMCID: PMC2219532.
10B. O'Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol. 2009 Jun 10;612(1-3):61-8. doi: 10.1016/j.ejphar.2009.03.010. Epub 2009 Mar 11. PMID: 19285060.
11B. Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011 Oct;2(4):236-40. doi: 10.4103/2231-4040.90879. PMID: 22247890; PMCID: PMC3255347.
33D. Takaishi M, Fujita F, Uchida K, Yamamoto S, Sawada Shimizu M, Hatai Uotsu C, Shimizu M, Tominaga M. 1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1. Mol Pain. 2012 Nov 29;8:86. doi: 10.1186/1744-8069-8-86. PMID: 23192000; PMCID: PMC3567430.
35D. Mahdavifard S, Nakhjavani M. 1,8 cineole protects type 2 diabetic rats against diabetic nephropathy via inducing the activity of glyoxalase-I and lowering the level of transforming growth factor-1β. J Diabetes Metab Disord. 2022 Mar 9;21(1):567-572. doi: 10.1007/s40200-022-01014-2. PMID: 35673442; PMCID: PMC9167362.
39D. National Institute of Diabetes and Digestive and Kidney Diseases. (n.d.). Low Blood Glucose (Hypoglycemia). National Institutes of Health. Retrieved June 14, 2024, from https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/low-blood-glucose-hypoglycemia
92E. Omari SA, Adams MJ, Geraghty DP. TRPV1 Channels in Immune Cells and Hematological Malignancies. Adv Pharmacol. 2017;79:173-198. doi: 10.1016/bs.apha.2017.01.002. Epub 2017 Mar 21. PMID: 28528668.
94E. Bertin S, Aoki-Nonaka Y, Lee J, de Jong PR, Kim P, Han T, Yu T, To K, Takahashi N, Boland BS, Chang JT, Ho SB, Herdman S, Corr M, Franco A, Sharma S, Dong H, Akopian AN, Raz E. The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1. Gut. 2017 Sep;66(9):1584-1596. doi: 10.1136/gutjnl-2015-310710. Epub 2016 Jun 20. PMID: 27325418; PMCID: PMC5173457.
95E. Acharya TK, Tiwari A, Majhi RK, Goswami C. TRPM8 channel augments T-cell activation and proliferation. Cell Biol Int. 2021 Jan;45(1):198-210. doi: 10.1002/cbin.11483. Epub 2020 Oct 30. PMID: 33090595.
93F. Yee NS, Zhou W, Lee M. Transient receptor potential channel TRPM8 is over-expressed and required for cellular proliferation in pancreatic adenocarcinoma. Cancer Lett. 2010 Nov 1;297(1):49-55. doi: 10.1016/j.canlet.2010.04.023. Epub 2010 Jun 1. PMID: 20605675; PMCID: PMC2933954.
94F. 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. PMID: 30061636.
95F. Cucu D, Chiritoiu G, Petrescu S, Babes A, Stanica L, Duda DG, Horii A, Dima SO, Popescu I. Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells. Pancreas. 2014 Jul;43(5):795-800. doi: 10.1097/MPA.0000000000000106. PMID: 24658318.
96F. Muller M, Haghnejad V, Schaefer M, Gauchotte G, Caron B, Peyrin-Biroulet L, Bronowicki JP, Neuzillet C, Lopez A. The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges. Cancers (Basel). 2022 Feb 16;14(4):995. doi: 10.3390/cancers14040995. PMID: 35205742; PMCID: PMC8870260.