Cannabinolic acids derivatives as a new anticancer drugs
Main Article Content
Abstract
Intensive research of the main products of the cannabis plant - tetrahydrocannabinolic (THCA) and cannabidiolic (CBDA) acids in recent years provided supportive evidence for their anti-inflammatory and anticancer activity, as well as the absence of any psychoactive properties. The presence of a carboxyl group in the cannabinoid acid molecules opens up a truly "Klondike" opportunity to obtain different derivatives and study their biological activity. This article is dedicated to description of some nitrogen containing THCA and CBDA derivatives and in vitro and in vivo anticancer activity of these compounds toward various cancer cell lines. A study of the cannabinoid influence on the hormesis effect in a HT-29 colon cancer cell line showed its direct dependence on the structure of both the cannabinoid moiety and the side chain substituents
Keywords:
THCA, CBDA, in vitro, in vivo, anticancer drugs
Article Details
How to Cite
AIZIKOVICH, Alexander.
Cannabinolic acids derivatives as a new anticancer drugs.
Medical Research Archives, [S.l.], v. 13, n. 6, june 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6575>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i6.6575.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Sievers RE, Rebits L. US2016228385.
3. Dibble CJ, Cole IB. US2017008870.
4. Flockhart I, Wheatley G, Drink S, Archer L. US20150203434.
5. Aizikovich A. US11472785B2.
6. Bruni N, Della Pepa C, Oliaro-Bosso S, et al. Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules. 2018;23:2478.
7. Jean-Gilles L, Gran B, Constantinescu CS. Interaction between cytokines, cannabinoids and the nervous system. Immunobiology. 2010; 215: 606–610.
8. Ghezzi P, Cerami A, Tumor necrosis factor as a pharmacological target. Molecular Biotechnology. 2005; 31: 239– 244..
9. Moreno-Sanz G. Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of D-Tetrahydrocannabinolic Acid A. Cannabis and Cannabinoid Research. 2016;1:124-130.
10. Formato M, Crescente G, Scognamiglio M, et al. (‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research. Molecules 2020; 25:2638.
11. Ruhaak LR. J Felth J, Karlsson PC et al. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol. Pharm. Bull. 2011;34:774—778.
12. Pellesi L, Licata M, Verri P et al. Pharmacokinetics and tolerability of oral cannabis preparations in patients with medication overuse headache (MOH) - a pilot study. Eur J of Clinical Pharm. 2018;74(11): 1427-1436
13. Zagzoog A, Mohamed KA, Kim HJJ et al. In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa. Nature research. 2020;10:20405.|
14. Sledzinski P, Nowak-Terpiłowska A, Zeyland J. Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases Int. J. Mol. Sci. 2021;22:263.
15. Cherkasova V, Wang B, Gerasymchuk M, Fiselier A, Kovalchuk O, Kovalchuk I. Use of Cannabis and Cannabinoids for Treatment of Cancer. Cancers 2022;14:5142.
16. Nigro E, M Formato M, Crescente G, Daniele A. Cancer Initiation, Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds? Molecules 2021;26:2668..
17. Aizikovich A. Cannabinoids and Cancer-What’s Next? Am J Biomed Sci & Res. 2021;14(3):234-236.
18. Formato M, Crescente G, Scognamiglio M, et al. (-)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research. Molecules 2020;25:2638.
19. Takeda S, Okazaki H, Ikeda E, et al. Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. J Toxicol Sci. 2014;39(5):711-6.
20. Ligresti A, Moriello AS, Starowicz K, et al. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 2006; 318(3):1375–1387.
21. Aizikovich A. US patent 2021008759.
22. Aizikovich A. In vitro Activity of Novel Cannabinoids Derived from Tetrahydrocan-nabinolic Acid on Various Human Tumor Cell Lines. J Oncology Res. 2021;2; 55-59.
23. Calabrese EJ. Cancer Biology and Hormesis: Human Tumor Cell Lines Commonly Display Hormetic (Biphasic) Dose Responses. Toxicology, 2005;35:463–582.
24. Yoshimasu T, Ohashi T, Oura S, et al. A Theoretical Model for the Hormetic Dose-response Curve for Anticancer Agents. Anticancer Res. 2015;35:5851-5856.
25 Burkhard H, Robert R. Cannabinoids as anticancer drugs: current status of preclinical Research. British Journal of Cancer 2022;127:1 – 13.
26. Lee H-S, Tamia G, Song H-J, Amarakoon D, et al. Cannabidiol exerts anti-proliferative activity via a cannabinoid receptor 2-dependent mechanism in human colorectal cancer cells. Int Immunopharmacol. 2022;108:108865.
27. Fowler CJ. Δ9-Tetrahydrocannabinol and cannabidiol as potential curative agents for cancer. A critical examination of the preclinical literature. Clinical Pharmacology & Therapeutics. 2015;97(6): 587–596.
28. Lorente M, Torres S, Salazar M, et al. Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action. Cell Death Differ. 2011;18(6):959–973.
29. Aizikovich A. Hormetic effects of in vitro anticancer activity of cannabinoid acid derivatives in the HT- colon cancer cell line. Int J Appl Sci & Res. 2023;6:27-30.
30. Aizikovich A. Anticancer Effect of New Cannabinoids Derived from Tetrahydrocannabinolic Acid on PANC-1 and AsPC-1 Human Pancreas Tumor Cells. J. Pancreatic Cancer. 2020;6:40-44.
31. Brauswetter D, Gurbi B, Varga A. Molecular subtype specific efficacy of MEK inhibitors in pancreatic cancers. PLOS ONE 2017; 28, 2017:1-13.