1Giusy Messina, 2Franco Rovelli, 3Paolo Lissoni
1,2,3International Institute of Pnei, Milan, Italy
ABSTRACT:
The endocannabinoid system plays a physiological natural anti-infiammatory anticancer role and the pharmacological effects of cannabinoids from Cannabis plant simply reflect the action of the endogenous ones. Therefore, from a therapeutic point of view Cannabis plant cannot be understood without taking into consideration the physio-pathological role of the endocannabinoid system. Despite the great number of potentially therapeutic molecules with the Cannabis plant, they may be synthetized within four archetypic molecules, which consist of tetra-hydro-cannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and cannabidiol (CBD). All molecules play a similar anticancer activity, whereas their psychological effects are different. THC is the only psychotropic psychedelic cannabinoid, whereas the other three cannabinoids have no psychotropic effect, but exert an important anxiolytic activity. Moreover, only THC acts as a direct enzyme responsible for cannabinoid degradation, by enhancing the endogenous cannabinoid content. Unfortunately, despite the great number of experimental studies, the clinical use of cannabinoids in the treatment of systemic human diseases is still at the beginning.
KEYWORDS:
Cannabidiol, Cannabigerol, Cannabinol, Cannabis plant, Cannabis therapy, Tetrahydrocannabinol
REFERENCES
1. Grotenhermen F. Pharmacology of cannabinoids. Neuroendocrinol Lett 25: 14-23, 2004.
2. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Magarkatti M. Cannabinoids as novel anti-inflammatry drugs. Front Med
Chem 1: 1333-1349, 2009.
3. Bogdanovic V, Mrdjanovic J, Borisev I. A review of the therapeutic antitumor potential of cannabinoids. J Altern
Complement Med 23: 831-836, 2017.
4. Hinz B, Ramer R. Anti-tumour actions of cannabinoids. Br J Pharmacol 176: 1384-1394, 2019.
5. Seltzer ES, Watters AK, MacKenzie D, Granat LM, Zhang D. Cannabidiol (CBD) as a promising anti-cancer drugs.
Cancers 12: 3203-3207, 2020.
6. Tomko AM, Whynot E, Ellis LD, Duprè DJ. Anticancer potential of cannabinoids, terpenes and flavonoids present in
Cannabis. Cancers 12: 1985-1991, 2020.
7. Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE. Effects of delt 9-tetrahydrocannabinol and cannabinol in
man. Pharmacology 13: 502-512, 1975.
8. Valenti M, Viganò D, Casico MG, Rubino T, steardo l, Parolaro D, Di Marzo V. Differential diurnal variation of
anandamide and 2-archidonyl-glycerol levels in rat brain. Cell mol life Sci 61: 945-950, 2004.
A Review of on the Psychobiological Differences Among Tetrahydrocannabinol, Cannabinol, Cannabidiol and
Cannabigerol
IJHMR, Volume 1 Issue 1 April 2022 www.ijhmr.com Page 39
9. Di Marzo V, Melck D, Orlando P, Bisogno T, Zagoory O, Bifulco M, Vogel Z, De Petrocellis L. Palmitoyl-ethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in
human breast cancer cells. Biochem J 358: 249-255, 2001.
10. Busquets-Garcia A, Puighermanal E, Pstor A, Della Torre R, Maldonado R, Ozaita A. Differential role of anandamide
and 2-arachidonylglycerol in memory and anxiety-like response. Biol psychiatry 70: 479-486, 2011.
11. Nachnani R, Raup-Konsavage WM, Vrana KE. The pharmacological case of cannabigerol. J Pharmacol Exp Ther 376:
204-212, 2021.
12. Bartsch C, Bartsch H. Melatonin in cancer patients and in tumor-bearing animals. Adv Exp Med Biol 467: 247-264, 1999.
13. Lissoni P, Resentini M, Mauri R, Esposti D, Esposti G, Rossi D, Legname G, Fraschini F. Effects of
tetrahydrocannabinol on melatonin secretion in man. Horm Metab Res 18: 77-78, 1986.
14. Sailler S, Schmitz K, Jager E, Ferreiros N, Wicker S, Zschiebsch K, picjert G, Geisslinger G, Walter C, Tageder I, Lotsch
J. Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans. Oncoscience
1: 272-282, 2014.
15. Zhang J, Zhang S, Liu Y, Su M, Ling X, Liu F, Ge Y, Bai M. Combined CD2 receptor agonist and photodynamic therapy
synergistically inhibit tumor growth in triple negative breast cancer. Photodiagnosis Photodyn Ther 24: 185-191, 2018.
16. Farrimond JA, Whalley BJ, Williams CM. Cannabinol and cannabidiol exert opposite effects on rat feeding patterns.
Psychopharmacology 223: 117-129, 2012.
17. Lah TT, Novak M, Pena Almidon MA, Marinelli O, Baskovic BZ, Majc B, Mlinar M, Bosnjak R, Breznik B, Zomer R,
Nabissi M. Cannabigerol is a potential therapeutic agent in a novel combined therapy for glioblastoma. Cells 10: 340-345,
2021.
18. Guindon J, Hohomann AG. The endocannabinoid system and cancer: therapeutic implication. Br J Pharmacol 163: 1447-
1463, 2011.
19. Ramer R, Hinz B. Cannabinoids as anticancer drugs. Adv Pharmacol 80: 397-436, 2017.
20. Ramer R, Schwarz R, Hinz B. Modulation of the endocannabinoid system as a potential anticancer strategy. Front
Pharmacol 10: 430-436, 2019.
21. Braile M, Marcella S, Maron G, Galdiero MR, Varricchi G, Loffredo S. The interplay between the immune and the
endocannabinoid systems in cancer. Cells 10: 1282-1287, 2021.
22. Lissoni P, Tintori A, Fumagalli L, Brivio F, Messina G, Parolini D, Biondi A, Balestra A, D’Amico G. The
endocannabinoid anandamide neither impairs in vitro T cell function or nduces regulatory T cell generation. Anticancer
Res 28: 3743-3748, 2008.
23. Hasseldam H, Johansen FF. Neuroprotection without immunomodulation is not sufficient to reduce first relapse severity
in experimental autoimmune encephalomyelitis. Neuroimmunomodulation 17: 252-264, 2010.
24. Cencioni MT, Chiurkiu V, Catanzaro G, Borsellino G, Bernardi G, Battistini L, Maccarrone M. Anandamide suppresses
proliferation and cytokine release from primary human T lymphocytes mainly via CB receptors. Plos One 5: e8688. doi:
10.1371/journal.pone.0008688, 2010.
25. Murugaiyan G, Saha B. Protumor vs antitumor functions of IL-17. J immunol 183: 4169-4175, 2009.
26. Tesar BM, Du W, Shirali AC, Walker WE, Shen H, Goldstein DR. Aging augments IL-17 T cell alloimmune responses.
Am J transplant 9: 54-63, 2008.
27. Sacerdote P, Martucci C, Vaccani A, Bariselli F, Panerai AE, Colombo A, Parolaro D, Massi P. the non-psychoactive
component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both
in vivo and in vitro. J Neuroimmunol 159: 97-105, 2005.
28. Mammana S, Cavalli E, gugliandolo A, Silvestro S, Pollastro F, Bramanti P, Mazzon E. Could the combination of two
non-psychotropic cannabinoids counteract neuroinflammation? Effectiveness of cannabidiol associated with
cannabigerol. Medicina 55: 747-751, 2019.
29. Lissoni P, Messina G, Pelizzoni F, Rovelli F, Brivio F, Monzon A, Crivelli N, Lissoni A, Tassoni S, Sassola A, Pensato S,
Di Fede G. the fascination of cytokine immunological science. J infectiology 3: 18-28, 2020.
30. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-actived killer cell phenomenon. J Exp Med 155:
1823-1841, 1982.
31. Banks RE, Patel PM, Selby PJ. Interleukin-12: a new clinical player in cytokine therapy. Br J Cancer 71: 655-659, 1995.
32. Chen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases (review). Mol Med Rep 23:
3391-3396, 2016.
33. Garcia-Arencibia M, Garcia C, Fernandez-Ruiz J. Cannabinoids and Parkin’s disease. CNS Neurol Disord Drug Targets
8: 432-439, 2009.
A Review of on the Psychobiological Differences Among Tetrahydrocannabinol, Cannabinol, Cannabidiol and
Cannabigerol
IJHMR, Volume 1 Issue 1 April 2022 www.ijhmr.com Page 40
34. Aso E, Ferrer I. Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Front Pharmacol 5: 37-41,
2014.
35. Cao C, Li Y, Liu H, Mayl J, Lin X, Sutherland K, Nabar N, Cai J. The potential therapeutic effects of THC on
Alzheimer’s disease. J Alzheimers Dis 42: 973-984, 2014.
36. Rieder CR. Cannabidiol in Parkinson’s disease. Braz J Psychiatry 42: 126-127, 2020.
37. Beurel E, Lowell JA. TH17 cells in depression. Brain Behav Immun 69: 28-34, 2017.
38. Vian J, Pereira C, Chavarria V, Kohler C, Stubbs B, Quevedo J, Klim SW, Carvalho AF, Berk M, Fernandes BS. The
renin-angiotensin system: a possible new target for depression. BMC Med 15: 144-150, 2017.
39. De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. Endocannabinoid signalling in the blood of
patients with schizofrenia. Lipids Health Dis 2: 5-9, 2003.
40. De Mello Schier AR, de Oliveira Riberio N, Coutinho DS, Machado S, Arias-Carrion O, Crippa JA, Zuardi AW, Nardi
AE, Silva AC. Antidepressant-like and anxiolytic-like effects of cannabidiol, a chimica compound from Cannabis sativa.
CNS Neurol Disord Drug Targets 13: 953-960, 2014.
41. Obermarnscheidt T, Miller NS. The impact of cannabidiol on psychiatric and medical conditions. J Clin Med Res 12;
303-403, 2020.
42. Berger AA, Keefe J, Winnick A, Gilbert E, Eskander JP, Yazdi C, Kaye AD, Viswanath O, Urits I. Cannabis and
cannabidiol (CBD) for the treatment of fibromyalgia. Best Pract Res Clin Anaesthes 34: 6617-631, 2020.
