The Endocannabinoid System (ECS): Comparison
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Enric I. Canela.

The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance of tissue and cellular homeostasis by functional fine-tuning of essential metabolic pathways is one of the key characteristics of the ECS. It is implicated in a variety of physiological and pathological states and an attractive pharmacological target yet to reach its full potential. 

  • endocannabinoid system
  • cancer
  • cannabinoid receptor
Please wait, diff process is still running!

References

  1. Tsuboi, K.; Uyama, T.; Okamoto, Y.; Ueda, N. Endocannabinoids and related N-acylethanolamines: Biological activities and metabolism. Inflamm. Regen. 2018, 38, 28.
  2. Stasiulewicz, A.; Znajdek, K.; Grudzień, M.; Pawiński, T.; Sulkowska, J.I. A guide to targeting the endocannabinoid system in drug design. Int. J. Mol. Sci. 2020, 21, 2778.
  3. Moreno, E.; Cavic, M.; Krivokuca, A.; Casadó, V.; Canela, E. The Endocannabinoid System as a Target in Cancer Diseases: Are We There Yet? Front. Pharmacol. 2019, 10, 339.
  4. Contino, M.; McCormick, P.J. Editorial: The Canonical and Non-Canonical Endocannabinoid System as a Target in Cancer and Acute and Chronic Pain. Front. Pharmacol. 2020, 11, 312.
  5. Alexander, S.P.H.; Kendall, D.A. The complications of promiscuity: Endocannabinoid action and metabolism. Br. J. Pharmacol. 2007, 152, 602–623.
  6. Watson, J.E.; Kim, J.S.; Das, A. Emerging class of omega-3 fatty acid endocannabinoids & their derivatives. Prostaglandins Other Lipid Mediat. 2019, 143, 106337.
  7. Veilleux, A.; Di Marzo, V.; Silvestri, C. The Expanded Endocannabinoid System/Endocannabinoidome as a Potential Target for Treating Diabetes Mellitus. Curr. Diab. Rep. 2019, 19, 117.
  8. HUGO(a), G.N.C. CNR1. Available online: (accessed on 15 July 2020).
  9. HUGO(b), G.N.C. CNR2. Available online: (accessed on 15 July 2020).
  10. The Human Protein Atlas Database V.20.0. Available online: (accessed on 3 March 2021).
  11. Uhlen, M.; Zhang, C.; Lee, S.; Sjöstedt, E.; Fagerberg, L.; Bidkhori, G.; Benfeitas, R.; Arif, M.; Liu, Z.; Edfors, F.; et al. A pathology atlas of the human cancer transcriptome. Science 2017, 357, 2507.
  12. Moreno, E.; Cavic, M.; Krivokuca, A.; Canela, E.I. The Interplay between Cancer Biology and the Endocannabinoid System-Significance for Cancer Risk, Prognosis and Response to Treatment. Cancers 2020, 12, 3275.
  13. Moreno, E.; Andradas, C.; Medrano, M.; Caffarel, M.M.; Pérez-Gómez, E.; Blasco-Benito, S.; Gómez-Cañas, M.; Pazos, M.R.; Irving, A.J.; Lluís, C.; et al. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. J. Biol. Chem. 2014, 289, 21960–21972.
  14. Blasco-Benito, S.; Moreno, E.; Seijo-Vila, M.; Tundidor, I.; Andradas, C.; Caffarel, M.M.; Caro-Villalobos, M.; Urigüen, L.; Diez-Alarcia, R.; Moreno-Bueno, G.; et al. Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer. Proc. Natl. Acad. Sci. USA 2019, 116, 3863–3872.
  15. Čavić, M.; Lluís, C.; Moreno, E.; Bakešová, J.; Canela, E.I.; Navarro, G. Production of functional recombinant G-protein coupled receptors for heteromerization studies. J. Neurosci. Methods 2011, 199, 258–264.
  16. Talevi, A.; Bellera, C.L. Challenges and opportunities with drug repurposing: Finding strategies to find alternative uses of therapeutics. Expert Opin. Drug Discov. 2020, 15, 397–401.
  17. Grahovac, J.; Srdić-Rajić, T.; Francisco Santibañez, J.; Pavlović, M.; Čavić, M.; Radulović, S. Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics. Cancer Biol. Med. 2019, 16, 247–263.
  18. Sultana, J.; Crisafulli, S.; Gabbay, F.; Lynn, E.; Shakir, S.; Trifirò, G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front. Pharmacol. 2020, 11, 1657.
  19. Cavic, M.; Krivokuca, A.; Boljevic, I.; Spasic, J.; Mihajlovic, M.; Pavlovic, M.; Damjanovic, A.; Radosavljevic, D.; Jankovic, R. Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals. Expert Rev. Mol. Diagn. 2021, 21, 101–107.
  20. Martínez, V.; Iriondo De-Hond, A.; Borrelli, F.; Capasso, R.; Del Castillo, M.D.; Abalo, R. Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals? Int. J. Mol. Sci. 2020, 21, 3067.
  21. Pagano, E.; Montanaro, V.; di Girolamo, A.; Pistone, A.; Altieri, V.; Zjawiony, J.K.; Izzo, A.A.; Capasso, R. Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol. Nat. Prod. Commun. 2015, 10.
  22. Cota, D.; Marsicano, G.; Tschöp, M.; Grübler, Y.; Flachskamm, C.; Schubert, M.; Auer, D.; Yassouridis, A.; Thöne-Reineke, C.; Ortmann, S.; et al. The endogenous cennabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J. Clin. Investig. 2003, 112, 423–431.
  23. Matias, I.; Gonthier, M.P.; Orlando, P.; Martiadis, V.; De Petrocellis, L.; Cervino, C.; Petrosino, S.; Hoareau, L.; Festy, F.; Pasquali, R.; et al. Regulation, function, and dysregulation of endocannabinoids in models of adipose and β-pancreatic cells and in obesity and hyperglycemia. J. Clin. Endocrinol. Metab. 2006, 91, 3171–3180.
  24. Pagano, C.; Pilon, C.; Calcagno, A.; Urbanet, R.; Rossato, M.; Milan, G.; Bianchi, K.; Rizzuto, R.; Bernante, P.; Federspil, G.; et al. The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J. Clin. Endocrinol. Metab. 2007, 92, 4810–4819.
  25. Vettor, R.; Pagano, C. The role of the endocannabinoid system in lipogenesis and fatty acid metabolism. Best Pract. Res. Clin. Endocrinol. Metab. 2009, 23, 51–63.
  26. Bouaboula, M.; Hilairet, S.; Marchand, J.; Fajas, L.; Le Fur, G.; Casellas, P. Anandamide induced PPARγ transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur. J. Pharmacol. 2005, 517, 174–181.
  27. Karaliota, S.; Siafaka-Kapadai, A.; Gontinou, C.; Psarra, K.; Mavri-Vavayanni, M. Anandamide increases the differentiation of rat adipocytes and causes PPARλ and cB1 receptor upregulation. Obesity 2009, 17, 1830–1838.
  28. Bielawiec, P.; Harasim-Symbor, E.; Chabowski, A. Phytocannabinoids: Useful Drugs for the Treatment of Obesity? Special Focus on Cannabidiol. Front. Endocrinol. 2020, 11, 114.
  29. Gallant, M.; Odei-Addo, F.; Frost, C.L.; Levendal, R.A. Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes. Phytomedicine 2009, 16, 942–949.
  30. Simon, V.; Cota, D. Mechanisms in endocrinology: Endocannabinoids and metabolism: Past, present and future. Eur. J. Endocrinol. 2017, 176, R309–R324.
  31. Malenczyk, K.; Keimpema, E.; Piscitelli, F.; Calvigioni, D.; Björklund, P.; Mackie, K.; Di Marzo, V.; Hökfelt, T.G.M.; Dobrzyn, A.; Harkany, T. Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture. Proc. Natl. Acad. Sci. USA 2015, 112, E6185–E6194.
  32. Osei-Hyiaman, D.; DePetrillo, M.; Pacher, P.; Liu, J.; Radaeva, S.; Bátkai, S.; Harvey-White, J.; Mackie, K.; Offertáler, L.; Wang, L.; et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J. Clin. Investig. 2005, 115, 1298–1305.
  33. Tam, J.; Cinar, R.; Liu, J.; Godlewski, G.; Wesley, D.; Jourdan, T.; Szanda, G.; Mukhopadhyay, B.; Chedester, L.; Liow, J.S.; et al. Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab. 2012, 16, 167–179.
  34. Cluny, N.L.; Vemuri, V.K.; Chambers, A.P.; Limebeer, C.L.; Bedard, H.; Wood, J.T.; Lutz, B.; Zimmer, A.; Parker, L.A.; Makriyannis, A.; et al. A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents. Br. J. Pharmacol. 2010, 161, 629–642.
  35. Tam, J.; Vemuri, V.K.; Liu, J.; Bátkai, S.; Mukhopadhyay, B.; Godlewski, G.; Osei-Hyiaman, D.; Ohnuma, S.; Ambudkar, S.V.; Pickel, J.; et al. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J. Clin. Investig. 2010, 120, 2953–2966.
  36. Perello, M.; Sakata, I.; Birnbaum, S.; Chuang, J.C.; Osborne-Lawrence, S.; Rovinsky, S.A.; Woloszyn, J.; Yanagisawa, M.; Lutter, M.; Zigman, J.M. Ghrelin Increases the Rewarding Value of High-Fat Diet in an Orexin-Dependent Manner. Biol. Psychiatry 2010, 67, 880–886.
  37. Gatta-Cherifi, B.; Matias, I.; Vallée, M.; Tabarin, A.; Marsicano, G.; Piazza, P.V.; Cota, D. Simultaneous postprandial deregulation of the orexigenic endocannabinoid anandamide and the anorexigenic peptide YY in obesity. Int. J. Obes. 2012, 36, 880–885.
  38. Monteleone, P.; Piscitelli, F.; Scognamiglio, P.; Monteleone, A.M.; Canestrelli, B.; Di Marzo, V.; Maj, M. Hedonic eating is associated with increased peripheral levels of ghrelin and the endocannabinoid 2-arachidonoyl-glycerol in healthy humans: A pilot study. J. Clin. Endocrinol. Metab. 2012, 97.
  39. Monteleone, A.M.; Di Marzo, V.; Monteleone, P.; Dalle Grave, R.; Aveta, T.; El Ghoch, M.; Piscitelli, F.; Volpe, U.; Calugi, S.; Maj, M. Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity. Eur. J. Nutr. 2016, 55, 1799–1805.
  40. Bellocchio, L.; Lafentre, P.; Cannich, A.; Cota, D.; Puente, N.; Grandes, P.; Chaouloff, F.; Piazza, P.V.; Marsicano, G. Bimodal control of stimulated food intake by the endocannabinoid system. Nat. Neurosci. 2010, 13, 281–283.
  41. Berge, K.; Piscitelli, F.; Hoem, N.; Silvestri, C.; Meyer, I.; Banni, S.; Di Marzo, V. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men. Lipids Health Dis. 2013, 12.
  42. Pintus, S.; Murru, E.; Carta, G.; Cordeddu, L.; Batetta, B.; Accossu, S.; Pistis, D.; Uda, S.; Ghiani, M.E.; Mele, M.; et al. Sheep cheese naturally enriched in α-linolenic, conjugated linoleic and vaccenic acids improves the lipid profile and reduces anandamide in the plasma of hypercholesterolaemic subjects. Br. J. Nutr. 2013, 109, 1453–1462.
  43. Almogi-Hazan, O.; Or, R. Cannabis, the endocannabinoid system and immunity—The journey from the bedside to the bench and back. Int. J. Mol. Sci. 2020, 21, 4448.
  44. Pereira, J.P.; An, J.; Xu, Y.; Huang, Y.; Cyster, J.G. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nat. Immunol. 2009, 10, 403–411.
  45. Hoggatt, J.; Pelus, L.M. Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking. Leukemia 2010, 24, 1993–2002.
  46. Maestroni, G.J.M. The endogenous cannabinoid 2-arachidonoyl glycerol as in vivo chemoattractant for dendritic cells and adjuvant for Th1 response to a soluble protein. FASEB J. 2004, 18, 1914–1916.
  47. Khuja, I.; Yekhtin, Z.; Or, R.; Almogi-Hazan, O. Cannabinoids reduce inflammation but inhibit lymphocyte recovery in murine models of bone marrow transplantation. Int. J. Mol. Sci. 2019, 20, 668.
  48. Robinson, R.H.; Meissler, J.J.; Breslow-Deckman, J.M.; Gaughan, J.; Adler, M.W.; Eisenstein, T.K. Cannabinoids inhibit T-cells via cannabinoid receptor 2 in an in vitro assay for graft rejection, the mixed lymphocyte reaction. J. Neuroimmune Pharmacol. 2013, 8, 1239–1250.
  49. Börner, C.; Höllt, V.; Kraus, J. Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription. Neuroimmunomodulation 2007, 14, 281–286.
  50. Chiurchiù, V.; Battistini, L.; Maccarrone, M. Endocannabinoid signalling in innate and adaptive immunity. Immunology 2015, 144, 352–364.
  51. Klein, T.W. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol. 2005, 5, 400–411.
  52. Leuti, A.; Fazio, D.; Fava, M.; Piccoli, A.; Oddi, S.; Maccarrone, M. Bioactive lipids, inflammation and chronic diseases. Adv. Drug Deliv. Rev. 2020, 159, 133–169.
  53. Murumalla, R.; Bencharif, K.; Gence, L.; Bhattacharya, A.; Tallet, F.; Gonthier, M.P.; Petrosino, S.; Di Marzo, V.; Cesari, M.; Hoareau, L.; et al. Effect of the Cannabinoid Receptor-1 antagonist SR141716A on human adipocyte inflammatory profile and differentiation. J. Inflamm. 2011, 8.
  54. Nissen, S.E.; Nicholls, S.J.; Wolski, K.; Rodés-Cabau, J.; Cannon, C.P.; Deanfield, J.E.; Després, J.P.; Kastelein, J.J.P.; Steinhubl, S.R.; Kapadia, S.; et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: The STRADIVARIUS randomized controlled trial. JAMA J. Am. Med. Assoc. 2008, 299, 1547–1560.
  55. Després, J.P.; Ross, R.; Boka, G.; Alméras, N.; Lemieux, I. Effect of rimonabant on the high-triglyceride/low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat the ADAGIO-lipids trial. Arterioscler. Thromb. Vasc. Biol. 2009, 29, 416–423.
  56. Deveaux, V.; Cadoudal, T.; Ichigotani, Y.; Teixeira-Clerc, F.; Louvet, A.; Manin, S.; Van Nhieu, J.T.; Belot, M.P.; Zimmer, A.; Even, P.; et al. Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS ONE 2009, 4.
  57. Agudo, J.; Martin, M.; Roca, C.; Molas, M.; Bura, A.S.; Zimmer, A.; Bosch, F.; Maldonado, R. Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. Diabetologia 2010, 53, 2629–2640.
  58. Chiurchiù, V.; van der Stelt, M.; Centonze, D.; Maccarrone, M. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases. Prog. Neurobiol. 2018, 160, 82–100.
  59. Hosking, R.D.; Zajicek, J.P. Therapeutic potential of cannabis in pain medicine. Br. J. Anaesth. 2008, 101, 59–68.
  60. Ligresti, A.; De Petrocellis, L.; Di Marzo, V. From phytocannabinoids to cannabinoid receptors and endocannabinoids: Pleiotropic physiological and pathological roles through complex pharmacology. Physiol. Rev. 2016, 96, 1593–1659.
  61. Costa, B.; Trovato, A.E.; Comelli, F.; Giagnoni, G.; Colleoni, M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur. J. Pharmacol. 2007, 556, 75–83.
  62. Shang, V.C.M.; O’Sullivan, S.E.; Kendall, D.A.; Roberts, R.E. The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite. Pharmacol. Res. 2016, 105, 152–163.
  63. Turcotte, C.; Blanchet, M.-R.; Laviolette, M.; Flamand, N. Impact of Cannabis, Cannabinoids, and Endocannabinoids in the Lungs. Front. Pharmacol. 2016, 7, 317.
  64. Turcotte, C.; Chouinard, F.; Lefebvre, J.S.; Flamand, N. Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites. J. Leukoc. Biol. 2015, 97, 1049–1070.
  65. Parlar, A.; Arslan, S.O.; Doğan, M.F.; Çam, S.A.; Yalçin, A.; Elibol, E.; Özer, M.K.; Üçkardeş, F.; Kara, H. The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress. Exp. Ther. Med. 2018, 16, 4900–4908.
  66. van Niekerk, G.; Mabin, T.; Engelbrecht, A.-M. Anti-inflammatory mechanisms of cannabinoids: An immunometabolic perspective. Inflammopharmacology 2019, 27, 39–46.
  67. Bozkurt, T.E. Endocannabinoid System in the Airways. Molecules 2019, 24, 4626.
  68. Melck, D.; De Petrocellis, L.; Orlando, P.; Bisogno, T.; Laezza, C.; Bifulco, M.; Marzo, V.D.I. Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology 2000, 141, 118–126.
  69. Fraguas-Sánchez, A.I.; Fernández-Carballido, A.; Torres-Suárez, A.I. Phyto-, endo- and synthetic cannabinoids: Promising chemotherapeutic agents in the treatment of breast and prostate carcinomas. Expert Opin. Investig. Drugs 2016, 25, 1311–1323.
  70. De Petrocellis, L.; Melck, D.; Palmisano, A.; Bisogno, T.; Laezza, C.; Bifulco, M.; Di Marzo, V. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc. Natl. Acad. Sci. USA 1998, 95, 8375–8380.
  71. Blázquez, C.; González-Feria, L.; Álvarez, L.; Haro, A.; Casanova, M.L.; Guzmán, M. Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas. Cancer Res. 2004, 64, 5617–5623.
  72. Sánchez, C.; de Ceballos, M.L.; Gomez del Pulgar, T.; Rueda, D.; Corbacho, C.; Velasco, G.; Galve-Roperh, I.; Huffman, J.W.; Ramón y Cajal, S.; Guzmán, M. Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor. Cancer Res. 2001, 61, 5784–5798.
  73. Ma, C.; Wu, T.T.; Jiang, P.C.; Li, Z.Q.; Chen, X.J.; Fu, K.; Wang, W.; Gong, R. Anti-carcinogenic activity of anandamide on human glioma in vitro and in vivo. Mol. Med. Rep. 2016, 13, 1558–1562.
  74. Fowler, C.J.; Jonsson, K.O.; Andersson, A.; Juntunen, J.; Järvinen, T.; Vandevoorde, S.; Lambert, D.M.; Jerman, J.C.; Smart, D. Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: Variability in response and involvement of arachidonic acid. Biochem. Pharmacol. 2003, 66, 757–767.
  75. Hinz, B.; Ramer, R.; Eichele, K.; Weinzierl, U.; Brune, K. Up-regulation of cyclooxygenase-2 expression is involved in R(+)-methanandamide-induced apoptotic death of human neuroglioma cells. Mol. Pharmacol. 2004, 66, 1643–1651.
  76. Hasenoehrl, C.; Feuersinger, D.; Sturm, E.M.; Bärnthaler, T.; Heitzer, E.; Graf, R.; Grill, M.; Pichler, M.; Beck, S.; Butcher, L.; et al. G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1. Int. J. Cancer 2018, 142, 121–132.
  77. Tutino, V.; Caruso, M.G.; De Nunzio, V.; Lorusso, D.; Veronese, N.; Gigante, I.; Notarnicola, M.; Giannelli, G. Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer. Cancers 2019, 11, 708.
  78. Raup-Konsavage, W.M.; Johnson, M.; Legare, C.A.; Yochum, G.S.; Morgan, D.J.; Vrana, K.E. Synthetic Cannabinoid Activity Against Colorectal Cancer Cells. Cannabis Cannabinoid Res. 2018, 3, 272–281.
  79. Martínez-Martínez, E.; Martín-Ruiz, A.; Martín, P.; Calvo, V.; Provencio, M.; García, J.M. CB2 cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway. Oncotarget 2016, 7, 68781–68791.
  80. Orellana-Serradell, O.; Poblete, C.E.; Sanchez, C.; Castellón, E.A.; Gallegos, I.; Huidobro, C.; Llanos, M.N.; Contreras, H.R. Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncol. Rep. 2015, 33, 1599–1608.
  81. Olea-Herrero, N.; Vara, D.; Malagarie-Cazenave, S.; Díaz-Laviada, I. Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R()-Methanandamide and JWH-015: Involvement of CB 2. Br. J. Cancer 2009, 101, 940–950.
  82. Coke, C.J.; Scarlett, K.A.; Chetram, M.A.; Jones, K.J.; Sandifer, B.J.; Davis, A.S.; Marcus, A.I.; Hinton, C.V. Simultaneous activation of induced heterodimerization between CXCR4 chemokine receptor and cannabinoid receptor 2 (CB2) reveals a mechanism for regulation of tumor progression. J. Biol. Chem. 2016, 291, 9991–10005.
  83. Ravi, J.; Elbaz, M.; Wani, N.A.; Nasser, M.W.; Ganju, R.K. Cannabinoid receptor-2 agonist inhibits macrophage induced EMT in non-small cell lung cancer by downregulation of EGFR pathway. Mol. Carcinog. 2016, 55, 2063–2076.
  84. Milian, L.; Mata, M.; Alcacer, J.; Oliver, M.; Sancho-Tello, M.; Martín de Llano, J.J.; Camps, C.; Galbis, J.; Carretero, J.; Carda, C. Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. PLoS ONE 2020, 15, e0228909.
  85. Preet, A.; Qamri, Z.; Nasser, M.W.; Prasad, A.; Shilo, K.; Zou, X.; Groopman, J.E.; Ganju, R.K. Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. Cancer Prev. Res. 2011, 4, 65–75.
  86. Engeli, S.; Böhnke, J.; Feldpausch, M.; Gorzelniak, K.; Janke, J.; Bátkai, S.; Pacher, P.; Harvey-White, J.; Luft, F.C.; Sharma, A.M.; et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes 2005, 54, 2838–2843.
  87. Blüher, M.; Engeli, S.; Klöting, N.; Berndt, J.; Fasshauer, M.; Bátkai, S.; Pacher, P.; Schön, M.R.; Jordan, J.; Stumvoll, M. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 2006, 55, 3053–3060.
  88. Côté, M.; Matias, I.; Lemieux, I.; Petrosino, S.; Alméras, N.; Després, J.P.; Di Marzo, V. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int. J. Obes. 2007, 31, 692–699.
  89. Di Marzo, V.; Verrijken, A.; Hakkarainen, A.; Petrosino, S.; Mertens, I.; Lundbom, N.; Piscitelli, F.; Westerbacka, J.; Soro-Paavonen, A.; Matias, I.; et al. Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects. Eur. J. Endocrinol. 2009, 161, 715–722.
  90. Abdulnour, J.; Yasari, S.; Rabasa-Lhoret, R.; Faraj, M.; Petrosino, S.; Piscitelli, F.; Prud’Homme, D.; Di Marzo, V. Circulating endocannabinoids in insulin sensitive vs. Insulin resistant obese postmenopausal women. A MONET group study. Obesity 2014, 22, 211–216.
  91. Hruby, A.; Hu, F.B. The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics 2015, 33, 673–689.
  92. Silvestri, C.; Di Marzo, V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab. 2013, 17, 475–490.
  93. Howlett, A.C. Pharmacology of cannabinoid receptors. Annu. Rev. Pharmacol. Toxicol. 1995, 35, 607–634.
  94. Pertwee, R.G.; Ross, R.A. Cannabinoid receptors and their ligands. Prostaglandins Leukot. Essent. Fat. Acids 2002, 66, 101–121.
  95. Lindborg, K.A.; Teachey, M.K.; Jacob, S.; Henriksen, E.J. Effects of in vitro antagonism of endocannabinoid-1 receptors on the glucose transport system in normal and insulin-resistant rat skeletal muscle. Diabetes Obes. Metab. 2010, 12, 722–730.
  96. Sam, A.H.; Salem, V.; Ghatei, M.A. Rimonabant: From RIO to Ban. J. Obes. 2011, 2011.
  97. Silvestri, C.; Di Marzo, V. Second generation CB1 receptor blockers and other inhibitors of peripheral endocannabinoid overactivity and the rationale of their use against metabolic disorders. Expert Opin. Investig. Drugs 2012, 21, 1309–1322.
  98. Matias, I.; Bisogno, T.; Di Marzo, V. Endogenous cannabinoids in the brain and peripheral tissues: Regulation of their levels and control of food intake. Int. J. Obes. 2006, 30, S7–S12.
  99. Tedesco, L.; Valerio, A.; Dossena, M.; Cardile, A.; Ragni, M.; Pagano, C.; Pagotto, U.; Carruba, M.O.; Vettor, R.; Nisoli, E. Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: The role of eNOS, p38 MAPK, and AMPK pathways. Diabetes 2010, 59, 2826–2836.
  100. Perwitz, N.; Wenzel, J.; Wagner, I.; Büning, J.; Drenckhan, M.; Zarse, K.; Ristow, M.; Lilienthal, W.; Lehnert, H.; Klein, J. Cannabinoid type 1 receptor blockade induces transdifferentiation towards a brown fat phenotype in white adipocytes. Diabetes Obes. Metab. 2010, 12, 158–166.
  101. Cinar, R.; Godlewski, G.; Liu, J.; Tam, J.; Jourdan, T.; Mukhopadhyay, B.; Harvey-White, J.; Kunos, G. Hepatic cannabinoid-1 receptors mediate diet-induced insulin resistance by increasing de novo synthesis of long-chain ceramides. Hepatology 2014, 59, 143–153.
  102. Chen, G.; Pang, Z. Endocannabinoids and Obesity. In Vitamins and Hormones; Academic Press Inc.: Cambridge, MA, USA, 2013; Volume 91, pp. 325–368.
  103. Jourdan, T.; Godlewski, G.; Cinar, R.; Bertola, A.; Szanda, G.; Liu, J.; Tam, J.; Han, T.; Mukhopadhyay, B.; Skarulis, M.C.; et al. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nat. Med. 2013, 19, 1132–1140.
  104. Gruden, G.; Barutta, F.; Kunos, G.; Pacher, P. Role of the endocannabinoid system in diabetes and diabetic complications. Br. J. Pharmacol. 2016, 173, 1116–1127.
  105. An, D.; Peigneur, S.; Hendrickx, L.A.; Tytgat, J. Targeting cannabinoid receptors: Current status and prospects of natural products. Int. J. Mol. Sci. 2020, 21, 5064.
  106. Yadav, M.R.; Murumkar, P.R. Advances in patented CB1 receptor antagonists for obesity. Pharm. Pat. Anal. 2018, 7, 169–173.
  107. Murphy, T.; Le Foll, B. Targeting the endocannabinoid CB1 receptor to treat body weight disorders: A preclinical and clinical review of the therapeutic potential of past and present CB1 drugs. Biomolecules 2020, 10, 855.
  108. Bauer, M.; Chicca, A.; Tamborrini, M.; Eisen, D.; Lerner, R.; Lutz, B.; Poetz, O.; Pluschke, G.; Gertsch, J. Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB 1 receptors. J. Biol. Chem. 2012, 287, 36944–36967.
  109. Vallée, M.; Vitiello, S.; Bellocchio, L.; Hebért-Chatelain, E.; Monlezun, S.; Martin-Garcia, E.; Kasanetz, F.; Baillie, G.L.; Panin, F.; Cathala, A.; et al. Pregnenolone can protect the brain from cannabis intoxication. Science 2014, 343, 94–98.
  110. Heimann, A.S.; Gomes, I.; Dale, C.S.; Pagano, R.L.; Gupta, A.; De Souza, L.L.; Luchessi, A.D.; Castro, L.M.; Giorgi, R.; Rioli, V.; et al. Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Proc. Natl. Acad. Sci. USA 2007, 104, 20588–20593.
  111. Dodd, G.T.; Mancini, G.; Lutz, B.; Luckman, S.M. The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice. J. Neurosci. 2010, 30, 7369–7376.
  112. Dodd, G.T.; Worth, A.A.; Hodkinson, D.J.; Srivastava, R.K.; Lutz, B.; Williams, S.R.; Luckman, S.M. Central functional response to the novel peptide cannabinoid, hemopressin. Neuropharmacology 2013, 71, 27–36.
  113. Macedonio, G.; Stefanucci, A.; Maccallini, C.; Mirzaie, S.; Novellino, E.; Mollica, A. Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools. Protein Pept. Lett. 2016, 23, 1045–1051.
  114. Mennella, I.; Ferracane, R.; Zucco, F.; Fogliano, V.; Vitaglione, P. Food liking enhances the plasma response of 2-arachidonoylglycerol and of pancreatic polypeptide upon modified sham feeding in humans. J. Nutr. 2015, 145, 2169–2175.
  115. Yoshida, R.; Ohkuri, T.; Jyotaki, M.; Yasuo, T.; Horio, N.; Yasumatsu, K.; Sanematsu, K.; Shigemura, N.; Yamamoto, T.; Margolskee, R.F.; et al. Endocannabinoids selectively enhance sweet taste. Proc. Natl. Acad. Sci. USA 2010, 107, 935–939.
  116. Soria-Gómez, E.; Bellocchio, L.; Reguero, L.; Lepousez, G.; Martin, C.; Bendahmane, M.; Ruehle, S.; Remmers, F.; Desprez, T.; Matias, I.; et al. The endocannabinoid system controls food intake via olfactory processes. Nat. Neurosci. 2014, 17, 407–415.
  117. Guida, M.; Ligresti, A.; De Filippis, D.; D’Amico, A.; Petrosino, S.; Cipriano, M.; Bifulco, G.; Simonetti, S.; Orlando, P.; Insabato, L.; et al. The Levels of the Endocannabinoid Receptor CB 2 and Its Ligand 2-Arachidonoylglycerol Are Elevated in Endometrial Carcinoma. Endocrinology 2010, 151, 921–928.
  118. Bermudez-Silva, F.J.; Viveros, M.P.; McPartland, J.M.; Rodriguez de Fonseca, F. The endocannabinoid system, eating behavior and energy homeostasis: The end or a new beginning? Pharmacol. Biochem. Behav. 2010, 95, 375–382.
  119. Buettner, C.; Muse, E.D.; Cheng, A.; Chen, L.; Scherer, T.; Pocai, A.; Su, K.; Cheng, B.; Li, X.; Harvey-White, J.; et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 2008, 14, 667–675.
  120. Sládek, M.; Liška, K.; Houdek, P.; Sumová, A. Modulation of single cell circadian response to NMDA by diacylglycerol lipase inhibition reveals a role of endocannabinoids in light entrainment of the suprachiasmatic nucleus. Neuropharmacology 2021, 185.
  121. Jumpertz, R.; Guijarro, A.; Pratley, R.E.; Piomelli, D.; Krakoff, J. Central and peripheral endocannabinoids and cognate acylethanolamides in humans: Association with race, adiposity, and energy expenditure. J. Clin. Endocrinol. Metab. 2011, 96, 787–791.
  122. Cedernaes, J.; Fanelli, F.; Fazzini, A.; Pagotto, U.; Broman, J.E.; Vogel, H.; Dickson, S.L.; Schiöth, H.B.; Benedict, C. Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans. Psychoneuroendocrinology 2016, 74, 258–268.
  123. Broussard, J.L.; Cauter, E. Van Disturbances of sleep and circadian rhythms: Novel risk factors for obesity. Curr. Opin. Endocrinol. Diabetes Obes. 2016, 23, 353–359.
  124. Wang, X.; Yu, Q.; Yue, H.; Zhang, J.; Zeng, S.; Cui, F. Circulating endocannabinoids and insulin resistance in patients with obstructive sleep apnea. Biomed Res. Int. 2016, 2016.
  125. Domingo-Rodriguez, L.; Ruiz de Azua, I.; Dominguez, E.; Senabre, E.; Serra, I.; Kummer, S.; Navandar, M.; Baddenhausen, S.; Hofmann, C.; Andero, R.; et al. A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction. Nat. Commun. 2020, 11.
  126. Di Marzo, V.; Silvestri, C. Lifestyle and metabolic syndrome: Contribution of the endocannabinoidome. Nutrients 2019, 11, 1956.
  127. Köse, S.; Aerts-Kaya, F.; Köprü, Ç.Z.; Nemutlu, E.; Kuşkonmaz, B.; Karaosmanoğlu, B.; Taşkıran, E.Z.; Altun, B.; Uçkan Çetinkaya, D.; Korkusuz, P. Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate in vitro hematopoietic stem cell migration effectively comparable to beta-adrenergic stimulation. Exp. Hematol. 2018, 57, 30–41.e1.
  128. Szabady, R.L.; Louissaint, C.; Lubben, A.; Xie, B.; Reeksting, S.; Tuohy, C.; Demma, Z.; Foley, S.E.; Faherty, C.S.; Llanos-Chea, A.; et al. Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis. J. Clin. Investig. 2018, 128, 4044–4056.
  129. Kapellos, T.S.; Taylor, L.; Feuerborn, A.; Valaris, S.; Hussain, M.T.; Rainger, G.E.; Greaves, D.R.; Iqbal, A.J. Cannabinoid receptor 2 deficiency exacerbates inflammation and neutrophil recruitment. FASEB J. 2019, 33, 6154–6167.
  130. 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, 232, 54–61.
  131. Lee, S.F.; Newton, C.; Widen, R.; Friedman, H.; Klein, T.W. Differential expression of cannabinoid CB2 receptor mRNA in mouse immune cell subpopulations and following B cell stimulation. Eur. J. Pharmacol. 2001, 423, 235–241.
  132. Sugamura, K.; Sugiyama, S.; Nozaki, T.; Matsuzawa, Y.; Izumiya, Y.; Miyata, K.; Nakayama, M.; Kaikita, K.; Obata, T.; Takeya, M.; et al. Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation 2009, 119, 28–36.
  133. Chiurchiù, V.; Lanuti, M.; Catanzaro, G.; Fezza, F.; Rapino, C.; Maccarrone, M. Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor. Atherosclerosis 2014, 233, 55–63.
  134. Staiano, R.I.; Loffredo, S.; Borriello, F.; Iannotti, F.A.; Piscitelli, F.; Orlando, P.; Secondo, A.; Granata, F.; Lepore, M.T.; Fiorelli, A.; et al. Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors. J. Leukoc. Biol. 2016, 99, 531–540.
  135. Miranda, K.; Mehrpouya-Bahrami, P.; Nagarkatti, P.S.; Nagarkatti, M. Cannabinoid receptor 1 blockade attenuates obesity and adipose tissue type 1 inflammation through miR-30e-5p regulation of delta-like-4 in macrophages and consequently downregulation of Th1 cells. Front. Immunol. 2019, 10.
  136. Xiang, W.; Shi, R.; Kang, X.; Zhang, X.; Chen, P.; Zhang, L.; Hou, A.; Wang, R.; Zhao, Y.; Zhao, K.; et al. Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression. Nat. Commun. 2018, 9.
  137. Espinosa-Riquer, Z.P.; Ibarra-Sánchez, A.; Vibhushan, S.; Bratti, M.; Charles, N.; Blank, U.; Rodríguez-Manzo, G.; González-Espinosa, C. TLR4 Receptor Induces 2-AG-Dependent Tolerance to Lipopolysaccharide and Trafficking of CB2 Receptor in Mast Cells. J. Immunol. 2019, 202, 2360–2371.
  138. Börner, C.; Smida, M.; Höllt, V.; Schraven, B.; Kraus, J. Cannabinoid receptor type 1- and 2-mediated increase in cyclic AMP inhibits T cell receptor-triggered signaling. J. Biol. Chem. 2009, 284, 35450–35460.
  139. Eisenstein, T.K.; Meissler, J.J.; Wilson, Q.; Gaughan, J.P.; Adler, M.W. Anandamide and Δ9-tetrahydrocannabinol directly inhibit cells of the immune system via CB2 receptors. J. Neuroimmunol. 2007, 189, 17–22.
  140. Janiak, P.; Poirier, B.; Bidouard, J.P.; Cadrouvele, C.; Pierre, F.; Gouraud, L.; Barbosa, I.; Dedio, J.; Maffrand, J.P.; Le Fur, G.; et al. Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats. Kidney Int. 2007, 72, 1345–1357.
  141. Aso, E.; Palomer, E.; Juvés, S.; Maldonado, R.; Muoz, F.J.; Ferrer, I. CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice. J. Alzheimers Dis. 2012, 30, 439–459.
  142. Croxford, J.L.; Pryce, G.; Jackson, S.J.; Ledent, C.; Giovannoni, G.; Pertwee, R.G.; Yamamura, T.; Baker, D. Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J. Neuroimmunol. 2008, 193, 120–129.
  143. Panikashvili, D.; Shein, N.A.; Mechoulam, R.; Trembovler, V.; Kohen, R.; Alexandrovich, A.; Shohami, E. The endocannabinoid 2-AG protects the blood-brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol. Dis. 2006, 22, 257–264.
  144. Buisseret, B.; Alhouayek, M.; Guillemot-Legris, O.; Muccioli, G.G. Endocannabinoid and Prostanoid Crosstalk in Pain. Trends Mol. Med. 2019, 25, 882–896.
  145. Fantauzzi, M.F.; Aguiar, J.A.; Tremblay, B.J.-M.; Mansfield, M.J.; Yanagihara, T.; Chandiramohan, A.; Revill, S.; Ryu, M.H.; Carlsten, C.; Ask, K.; et al. Expression of endocannabinoid system components in human airway epithelial cells: Impact of sex and chronic respiratory disease status. ERJ Open Res. 2020, 6, 128–2020.
  146. Tahamtan, A.; Samieipoor, Y.; Nayeri, F.S.; Rahbarimanesh, A.A.; Izadi, A.; Rashidi-Nezhad, A.; Tavakoli-Yaraki, M.; Farahmand, M.; Bont, L.; Shokri, F.; et al. Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice. Virulence 2018, 9, 217–230.
  147. Cinar, R.; Gochuico, B.R.; Iyer, M.R.; Jourdan, T.; Yokoyama, T.; Park, J.K.; Coffey, N.J.; Pri-Chen, H.; Szanda, G.; Liu, Z.; et al. Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of idiopathic pulmonary fibrosis. JCI Insight 2017, 2, e92281.
  148. Balenga, N.A.B.; Aflaki, E.; Kargl, J.; Platzer, W.; Schröder, R.; Blättermann, S.; Kostenis, E.; Brown, A.J.; Heinemann, A.; Waldhoer, M. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res. 2011, 21, 1452–1469.
  149. Chatkin, J.M.; Zani-Silva, L.; Ferreira, I.; Zamel, N. Cannabis-Associated Asthma and Allergies. Clin. Rev. Allergy Immunol. 2019, 56, 196–206.
  150. Vuolo, F.; Abreu, S.C.; Michels, M.; Xisto, D.G.; Blanco, N.G.; Hallak, J.E.; Zuardi, A.W.; Crippa, J.A.; Reis, C.; Bahl, M.; et al. Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur. J. Pharmacol. 2019, 843, 251–259.
  151. Wawryk-Gawda, E.; Chłapek, K.; Zarobkiewicz, M.K.; Lis-Sochocka, M.; Chylińska-Wrzos, P.; Boguszewska-Czubara, A.; Sławiński, M.A.; Franczak, A.; Jodłowska-Jędrych, B.; Biała, G. CB2R agonist prevents nicotine induced lung fibrosis. Exp. Lung Res. 2018, 44, 344–351.
  152. Byrareddy, S.N.; Mohan, M. SARS-CoV2 induced respiratory distress: Can cannabinoids be added to anti-viral therapies to reduce lung inflammation? Brain. Behav. Immun. 2020, 87, 120–121.
  153. Costiniuk, C.T.; Jenabian, M.-A. Acute inflammation and pathogenesis of SARS-CoV-2 infection: Cannabidiol as a potential anti-inflammatory treatment? Cytokine Growth Factor Rev. 2020, 53, 63–65.
  154. Onaivi, E.S.; Sharma, V. Cannabis for COVID-19: Can cannabinoids quell the cytokine storm? Future Sci. OA 2020, 6, FSO625.
  155. Caffarel, M.M.; Andradas, C.; Mira, E.; Pérez-Gómez, E.; Cerutti, C.; Moreno-Bueno, G.; Flores, J.M.; García-Real, I.; Palacios, J.; Mañes, S.; et al. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol. Cancer 2010, 9.
  156. Nasser, M.W.; Qamri, Z.; Deol, Y.S.; Smith, D.; Shilo, K.; Zou, X.; Ganju, R.K. Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS ONE 2011, 6.
  157. Faubert, B.; Solmonson, A.; DeBerardinis, R.J. Metabolic reprogramming and cancer progression. Science 2020, 368.
  158. Chen, X.; Yi, C.; Yang, M.-J.; Sun, X.; Liu, X.; Ma, H.; Li, Y.; Li, H.; Wang, C.; He, Y.; et al. Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions. J. Cancer 2021, 12, 1563–1574.
  159. Romero-Garcia, S.; Lopez-Gonzalez, J.S.; Báez-Viveros, J.L.; Aguilar-Cazares, D.; Prado-Garcia, H. Tumor cell metabolism: An integral view. Cancer Biol. Ther. 2011, 12, 939–948.
  160. Mijatović, S.; Savić-Radojević, A.; Plješa-Ercegovac, M.; Simić, T.; Nicoletti, F.; Maksimović-Ivanić, D. The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors. Antioxidants 2020, 9, 374.
  161. Kienzl, M.; Kargl, J.; Schicho, R. The Immune Endocannabinoid System of the Tumor Microenvironment. Int. J. Mol. Sci. 2020, 21, 8929.
  162. Koundouros, N.; Poulogiannis, G. Reprogramming of fatty acid metabolism in cancer. Br. J. Cancer 2020, 122, 4–22.
  163. Ghasemiesfe, M.; Barrow, B.; Leonard, S.; Keyhani, S.; Korenstein, D. Association between Marijuana Use and Risk of Cancer: A Systematic Review and Meta-analysis. JAMA Netw. Open 2019, 2, e1916318.
  164. Jankovic, R.; J Goncalves, H.; Cavic, M.; Clemente, C.; Lind, M.; Murillo Carrasco, A.; Nadifi, S.; Khyatti, M.; Adebambo, T.; Egamberdiev, D. LungCARD—Report on worldwide research and clinical practices related to lung cancer. J. BUON 2019, 24, 11–19.
  165. Caffarel, M.M.; Andradas, C.; Pérez-Gómez, E.; Guzmán, M.; Sánchez, C. Cannabinoids: A new hope for breast cancer therapy? Cancer Treat. Rev. 2012, 38, 911–918.
  166. Caffarel, M.M.; Sarrió, D.; Palacios, J.; Guzmán, M.; Sánchez, C. Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006, 66, 6615–6621.
  167. Qamri, Z.; Preet, A.; Nasser, M.W.; Bass, C.E.; Leone, G.; Barsky, S.H.; Ganju, R.K. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol. Cancer Ther. 2009, 8, 3117–3129.
  168. Malhotra, P.; Casari, I.; Falasca, M. Therapeutic potential of cannabinoids in combination cancer therapy. Adv. Biol. Regul. 2021, 100774.
  169. McAllister, S.D.; Murase, R.; Christian, R.T.; Lau, D.; Zielinski, A.J.; Allison, J.; Almanza, C.; Pakdel, A.; Lee, J.; Limbad, C.; et al. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res. Treat. 2011, 129, 37–47.
  170. Mohammadpour, F.; Ostad, S.N.; Aliebrahimi, S.; Daman, Z. Anti-invasion Effects of Cannabinoids Agonist and Antagonist on Human Breast Cancer Stem Cells. Iran. J. Pharm. Res. IJPR 2017, 16, 1479–1486.
  171. Marcu, J.P.; Christian, R.T.; Lau, D.; Zielinski, A.J.; Horowitz, M.P.; Lee, J.; Pakdel, A.; Allison, J.; Limbad, C.; Moore, D.H.; et al. Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol. Cancer Ther. 2010, 9, 180–189.
  172. Velasco, G.; Carracedo, A.; Blázquez, C.; Lorente, M.; Aguado, T.; Haro, A.; Sánchez, C.; Galve-Roperh, I.; Guzmán, M. Cannabinoids and gliomas. Mol. Neurobiol. 2007, 36, 60–67.
  173. Pagano, E.; Borrelli, F.; Orlando, P.; Romano, B.; Monti, M.; Morbidelli, L.; Aviello, G.; Imperatore, R.; Capasso, R.; Piscitelli, F.; et al. Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis. Pharmacol. Res. 2017, 119, 227–236.
  174. Scarlett, K.A.; White, E.S.Z.; Coke, C.J.; Carter, J.R.; Bryant, L.K.; Hinton, C.V. Agonist-induced CXCR4 and CB2 heterodimerization inhibits Ga13/ RhoA-mediated migration. Mol. Cancer Res. 2018, 16, 728–739.
  175. Fraguas-Sánchez, A.I.; Torres-Suárez, A.I. Medical Use of Cannabinoids. Drugs 2018, 78, 1665–1703.
  176. Cavic, M.; Spasic, J.; Krivokuca, A.; Boljevic, I.; Kuburovic, M.; Radosavljevic, D.; Jankovic, R. TP53 and DNA-repair gene polymorphisms genotyping as a low-cost lung adenocarcinoma screening tool. J. Clin. Pathol. 2019, 72, 75–80.
  177. Chen, R.; Manochakian, R.; James, L.; Azzouqa, A.-G.; Shi, H.; Zhang, Y.; Zhao, Y.; Zhou, K.; Lou, Y. Emerging therapeutic agents for advanced non-small cell lung cancer. J. Hematol. Oncol. 2020, 13, 58.
  178. Srdic-Rajic, T.; Santibañez, J.F.; Kanjer, K.; Tisma-Miletic, N.; Cavic, M.; Galun, D.; Jevric, M.; Kardum, N.; Konic-Ristic, A.; Zoranovic, T. Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells. Sci. Rep. 2017, 7, 3763.
  179. McAllister, S.D.; Soroceanu, L.; Desprez, P.-Y. The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids. J. Neuroimmune Pharmacol. 2015, 10, 255–267.
  180. Skorić, M.; Gligorijević, N.; Čavić, M.; Todorović, S.; Janković, R.; Ristić, M.; Mišić, D.; Radulović, S. Cytotoxic activity of Nepeta rtanjensis Diklić & Milojević essential oil and its mode of action. Ind. Crops Prod. 2017, 100, 163–170.
  181. Laezza, C.; Pagano, C.; Navarra, G.; Pastorino, O.; Proto, M.C.; Fiore, D.; Piscopo, C.; Gazzerro, P.; Bifulco, M. The Endocannabinoid System: A Target for Cancer Treatment. Int. J. Mol. Sci. 2020, 21, 747.
  182. Lah, T.T.; Novak, M.; Pena Almidon, M.A.; Marinelli, O.; Žvar Baškovič, B.; Majc, B.; Mlinar, M.; Bošnjak, R.; Breznik, B.; Zomer, R.; et al. Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma. Cells 2021, 10, 340.
More
ScholarVision Creations