The endocannabinod system is expressed in the gastrointestinal tract including CB1, CB2, PPAR-α, TRPV1, GPR119 and GPR55 receptors. endocannabinoids AEA, PEA and OEA are biosynthesized in the gastrointestinal tract where they modulate several processes of it through the interaction with the endocannabinoid receptors (Borrelli & Izzo, 2009; Izzo, Muccioli, Ruggieri, & Schicho, 2015; Taschler, Hasenoehrl, Storr, & Schicho, 2016)

Plant cannabinoids also modulate transit and motility of the gastrointestinal tract in rats (Shook & Burks, 1989)

GPR12 has been related to the modulation of metastasis process in cancer cells and CBD acts as inverse agonist of it (Brown, Laun, & Song, 2017)

THC has been reported to ameliorate nausea and vomiting symptoms related to gastric cancer (Gonzalez-Rosales & Walsh, 1997)

Low doses of AEA induce cell growth in gastric cancer cells while high doses of AEA have the opposite effect. However, when the anticancer drug Paclitaxel is coadministered with AEA, only high doses of AEA have an effect on cell growth, reducing gastric cancer cell viability (Miyato et al., 2009)

Synthetic CB1 agonist WIN 55,212-2 showed antineoplastic and antiproliferative effects in both animal models and in vitro assays of gastric cancer and has been proposed as an alternative to 5-Fluorouracil resistant gastric cancer cells (Oh et al., 2013; Park et al., 2011; X. Xian et al., 2016; X.-S. Xian et al., 2010; X.-S. Xian, Park, Choi, & Park, 2013)

Synthetic and endogenous cannabinoid agonists AEA, METH-AEA CP showed similar effects in reducing cell viability of gastric cancer cells in vitro (Ortega et al., 2016)

Literature:

Borrelli, F., & Izzo, A. A. (2009). Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance. Best Practice & Research Clinical Endocrinology & Metabolism, 23(1), 33-49. https://doi.org/10.1016/j.beem.2008.10.003

Brown, K. J., Laun, A. S., & Song, Z.-H. (2017). Cannabidiol, a novel inverse agonist for GPR12. Biochemical and Biophysical Research Communications, 493(1), 451-454. https://doi.org/10.1016/j.bbrc.2017.09.001

Gonzalez-Rosales, F., & Walsh, D. (1997). Intractable nausea and vomiting due to gastrointestinal mucosal metastases relieved by tetrahydrocannabinol (dronabinol). Journal of pain and Symptom Management, 14(5), 311-314. https://doi.org/10.1016/S0885-3924(97)00229-7

Izzo, A. A., Muccioli, G. G., Ruggieri, M. R., & Schicho, R. (2015). endocannabinoids and the Digestive Tract and Bladder in Health and Disease. En R. G. Pertwee (Ed.), endocannabinoids (pp. 423-447). Springer International Publishing. https://doi.org/10.1007/978-3-319-20825-1_15

Miyato, H., Kitayama, J., Yamashita, H., Souma, D., Asakage, M., Yamada, J., & Nagawa, H. (2009). Pharmacological Synergism Between cannabinoids and Paclitaxel in Gastric cancer Cell Lines. Journal of Surgical Research, 155(1), 40-47. https://doi.org/10.1016/j.jss.2008.06.045

Oh, J. H., Lee, J. Y., Baeg, M. K., Han, K.-H., Choi, M.-G., & Park, J. M. (2013). Antineoplastic Effect of WIN 55,212-2, a cannabinoid Agonist, in a Murine Xenograft Model of Gastric cancer. Chemotherapy, 59(3), 200-206. https://doi.org/10.1159/000355666

Ortega, A., García-Hernández, V. M., Ruiz-García, E., Meneses-García, A., Herrera-Gómez, A., Aguilar-Ponce, J. L., … Del Angel, S. A. (2016). Comparing the effects of endogenous and synthetic cannabinoid receptor agonists on survival of gastric cancer cells. Life Sciences, 165(Supplement C), 56-62. https://doi.org/10.1016/j.lfs.2016.09.010

Park, J. M., Xian, X.-S., Choi, M.-G., Park, H., Cho, Y. K., Lee, I. S., … Chung, I.-S. (2011). Antiproliferative mechanism of a cannabinoid agonist by cell cycle arrest in human gastric cancer cells. Journal of Cellular Biochemistry, 112(4), 1192-1205. https://doi.org/10.1002/jcb.23041

Shook, J. E., & Burks, T. F. (1989). Psychoactive cannabinoids reduce gastrointestinal propulsion and motility in rodents. The Journal of Pharmacology and Experimental Therapeutics, 249(2), 444-449.

Taschler, U., Hasenoehrl, C., Storr, M., & Schicho, R. (2016). cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance. En Gastrointestinal Pharmacology (pp. 343-362). Springer, Cham. https://doi.org/10.1007/164_2016_105

Xian, X., Huang, L., Zhang, B., Wu, C., Cui, J., & Wang, Z. (2016). WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric cancer Cells via COX-2 Signals. Cellular Physiology and Biochemistry, 39(6), 2149-2157. https://doi.org/10.1159/000447910

Xian, X.-S., Park, H., Cho, Y. K., Lee, I. S., Kim, S. W., Choi, M.-G., … Park, J. M. (2010). Effect of a synthetic cannabinoid agonist on the proliferation and invasion of gastric cancer cells. Journal of Cellular Biochemistry, 110(2), 321-332. https://doi.org/10.1002/jcb.22540

Xian, X.-S., Park, H., Choi, M.-G., & Park, J. M. (2013). cannabinoid receptor agonist as an alternative drug in 5-fluorouracil-resistant gastric cancer cells. Anticancer Research, 33(6), 2541-2547.