Article by Justin L Scharton, Independent Researcher
Article written on March 5, 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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Cannabinoids & Terpenes in Prostate Cancer:
From TRPM8 Antagonists to COX-2 Inhibitors
Receptors and Signaling Pathways in Prostate Cancer
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TRPM8 Overexpression
TRPM8 is upregulated in prostate cancer cells, and inhibition of TRPM8 reduces prostate cancer cell growth. (63F)
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CB1 and CB2 Receptors
Both CB1 and CB2 can be overexpressed in prostate cancer. Cannabinoid receptor stimulation (or inhibition) may influence tumor viability, apoptosis, and androgen signaling. (64F)
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PI3K/PTEN/Akt/mTOR and Raf/MEK/ERK
These pathways are frequently activated in prostate cancer. Interrupting these pathways can limit cell growth, survival, and metastatic spread. (65F)
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COX-2
Selectively inhibiting COX-2 in prostate cancer cell lines triggers apoptosis in vitro and in vivo. (65F)
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Cannabinoids and Terpenes Affecting TRPM8
Cannabinoids that are antagonists of TRPM8: CBC, CBG, CBD, CBN, THC, THCA, THCV, CBDV, CBDA, THCVA, CBGV. (3A 19A 54A)
TRPM8 antagonism may help suppress prostate cancer cell growth. (67F)
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Eucalyptol (Agonist)
Eucalyptol is a TRPM8 agonist,(33D) which might increase ion flow and worsen certain prostate cancers overexpressing TRPM8. Eucalyptol also shows cytotoxic effects in prostate cancer overexpressing ANXA7, downregulating MDM4, NF-κB, and VEGF. (68F) It could still exhibit anti-cancer properties in ANXA7-positive cells.
There are other terpenes that would be a better choice until research can prove that eucalyptol has anti-cancer effects for the prostate.
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Specific Terpenes and Their Targets for Prostate Cancer
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Limonene
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Reduces p-Akt (Ser473 and Thr308) and p-GSK-3β (Ser9). (97B)
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Activates caspase-3, caspase-9, and PARP while increasing BAX and cytochrome C. (97B)
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Decreases Bcl-2, collectively promoting apoptosis. (97B)
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Carvacrol
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Impacts PI3K/AKT/mTOR, MAPK, STAT3, and Notch signaling. (21E)
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Inhibits migration, invasion, and angiogenesis in tumor cells. (18E)
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Also acts as a COX-2 inhibitor. (18E)
Other Terpenes Interacting with COX-2
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(-)-α-Bisabolol: COX-2 modulator. (62D)
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Geraniol: COX-2 inhibitor. (77D)
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Eugenol: COX-2 modulator or expression inhibitor. (68E)
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Using Raw Cannabis and THCA to Antagonize TRPM8
Raw cannabis is full of THCA, which is a TRPM8 antagonist. Raw Cannabis and THCA THCA is non-psychoactive yet still exerts physiological effects, often aided by terpenes in the plant. Raw cannabis can be consumed by placing it in a capsule or brewing it into a hot-water tea using dried buds.
Soaking the bud in hot water for about 10 minutes will soften it, allowing it to be chewed and swallowed for maximum dose. They are gummy and takes a while to chew Even a small amount (¼–½â€¯gram) may be sufficient, and can be taken several times per day which is more tolerable than large doses.
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Cannabis Leaves for THCA
Leaves have THCA and other cannabinoids. Soaking a leaf in hot water is another option. Large leaves can be overpowering. Taking a few pieces of a large leaf, or using a few small leaves and be more tolerable. Chew the soaked leaf after softening in hot water, repeating this process several times per day if needed. Adding lemon juice to the water speeds leaf breakdown, making it easier to chew. Eating the leaves can help stretch your supply if you run low on cannabis while waiting for new plants to grow.
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Combining THCA with CBD and Other Terpenes
For prostate cancer, synergizing THCA with CBD, plus specific herbs or terpenes, may interrupt multiple cell signals (such as TRPM8 antagonism) and potentially enhance the anti-cancer effect.
See Breast Cancer section for dosing information.
Sources
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3A. Muller C, Morales P, Reggio PH. Cannabinoid Ligands Targeting TRP Channels. Front Mol Neurosci. 2019 Jan 15;11:487. doi: 10.3389/fnmol.2018.00487. PMID: 30697147; PMCID: PMC6340993.
19A. De Petrocellis L., Ligresti A., Moriello A. S., Allarà M., Bisogno T., Petrosino S., et al.. (2011b). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163, 1479–1494. 10.1111/j.1476-5381.2010.01166.x
54A. De Petrocellis L., Starowicz K., Moriello A. S., Vivese M., Orlando P., Di Marzo V. (2007). Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB1 receptors and endovanilloids. Exp. Cell Res. 313, 1911–1920. 10.1016/j.yexcr.2007.01.008
97B. Jia SS, Xi GP, Zhang M, Chen YB, Lei B, Dong XS, Yang YM. Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells. Oncol Rep. 2013 Jan;29(1):349-54. doi: 10.3892/or.2012.2093. Epub 2012 Oct 19. PMID: 23117412.
62D. Javed H, Meeran MFN, Azimullah S, Bader Eddin L, Dwivedi VD, Jha NK, Ojha S. α-Bisabolol, a Dietary Bioactive Phytochemical Attenuates Dopaminergic Neurodegeneration through Modulation of Oxidative Stress, Neuroinflammation and Apoptosis in Rotenone-Induced Rat Model of Parkinson's disease. Biomolecules. 2020 Oct 8;10(10):1421. doi: 10.3390/biom10101421. PMID: 33049992; PMCID: PMC7599960.
77D. Katsukawa M, Nakata R, Koeji S, Hori K, Takahashi S, Inoue H. Citronellol and geraniol, components of rose oil, activate peroxisome proliferator-activated receptor α and γ and suppress cyclooxygenase-2 expression. Biosci Biotechnol Biochem. 2011;75(5):1010-2. doi: 10.1271/bbb.110039. Epub 2011 May 20. PMID: 21597168.
18E. Yousef EH, Abo El-Magd NF, El Gayar AM. Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7. Life Sci. 2023 Jul 1;324:121735. doi: 10.1016/j.lfs.2023.121735. Epub 2023 May 2. PMID: 37142088.
21E. Singh J, Luqman S, Meena A. Carvacrol as a Prospective Regulator of Cancer Targets/Signalling Pathways. Curr Mol Pharmacol. 2023 Mar 27;16(5):542-558. doi: 10.2174/1874467215666220705142954. PMID: 35792130.
68E. Fathy M, Fawzy MA, Hintzsche H, Nikaido T, Dandekar T, Othman EM. Eugenol Exerts Apoptotic Effect and Modulates the Sensitivity of HeLa Cells to Cisplatin and Radiation. Molecules. 2019 Nov 3;24(21):3979. doi: 10.3390/molecules24213979. PMID: 31684176; PMCID: PMC6865178.
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63F. Valero ML, Mello de Queiroz F, Stühmer W, Viana F, Pardo LA. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. PLoS One. 2012;7(12):e51825. doi: 10.1371/journal.pone.0051825. Epub 2012 Dec 14. PMID: 23251635; PMCID: PMC3522609.
64F. Sarfaraz S, Afaq F, Adhami VM, Mukhtar H. Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res. 2005 Mar 1;65(5):1635-41. doi: 10.1158/0008-5472.CAN-04-3410. PMID: 15753356.
65F. Lee JT, Lehmann BD, Terrian DM, Chappell WH, Stivala F, Libra M, Martelli AM, Steelman LS, McCubrey JA. Targeting prostate cancer based on signal transduction and cell cycle pathways. Cell Cycle. 2008 Jun 15;7(12):1745-62. doi: 10.4161/cc.7.12.6166. Epub 2008 Jun 16. PMID: 18594202; PMCID: PMC2593475.
66F. Kirschenbaum A, Liu X, Yao S, Levine AC. The role of cyclooxygenase-2 in prostate cancer. Urology. 2001 Aug;58(2 Suppl 1):127-31. doi: 10.1016/s0090-4295(01)01255-9. PMID: 11502467.
67F. Di Donato M, Ostacolo C, Giovannelli P, Di Sarno V, Monterrey IMG, Campiglia P, Migliaccio A, Bertamino A, Castoria G. Therapeutic potential of TRPM8 antagonists in prostate cancer. Sci Rep. 2021 Dec 1;11(1):23232. doi: 10.1038/s41598-021-02675-4. PMID: 34853378; PMCID: PMC8636514.
68F. Leighton X, Bera A, Eidelman O, Eklund M, Puthillathu N, Pollard HB, Srivastava M. High ANXA7 Potentiates Eucalyptol Toxicity in Hormone-refractory Prostate Cancer. Anticancer Res. 2018 Jul;38(7):3831-3842. doi: 10.21873/anticanres.12667. PMID: 29970503.