Reviews

Vol. 2 (2025): Trends in Pharmacy

Therapeutic Potential of Cannabis Plant in Diabetes

Main Article Content

Zeynep Mine Coşkun Yazıcı
Işıl Sezekler

Abstract

Abstract: Diabetes mellitus (DM) is a metabolic disorder of the endocrine system that poses a serious threat to human health. Although many chemical substances are available for the prevention and treatment of DM and its complications, an optimal treatment for diabetes is not yet available. As an alternative to these synthetic substances, plants are widely used in various traditional medicine systems for the prevention of diabetes. Cannabis sativa L., a member of the Cannabaceae family, is one of the plants with very ancient medicinal use. More than 100 phytocannabinoids have been identified in C. sativa, most notably Δ9-tetrahydrocannabinol and cannabidiol. In addition to cannabinoids, cannabis also contains terpenoids and flavonoids. Various studies have shown that these compounds have many therapeutic effects such as antioxidant, analgesic, immunomodulatory, and anticonvulsant. This review provides an overview of the therapeutic effects of the cannabis plant and its constituents on diabetes and its complications.

Cite this article as: Yazıcı Coşkun ZM & Sezekler I. Therapeutic potential of cannabis
plant in diabetes. Trends in Pharmacy, 2025, 2, 0005, doi: 10.5152/ TrendsPharm.2025.25005.

Article Details

References

1. World Health Organization. Available at: https://www.who.int.

Accessed February 25, 2025.

2. International Diabetes Federation. Available at: https://diabetesatlas.org. Accessed February 25, 2025.

3. Młynarska E, Czarnik W, Dzieża N, et al. Type 2 diabetes mellitus: new pathogenetic mechanisms, treatment and the most

important complications. Int J Mol Sci. 2025;26(3):1094.

[CrossRef]

4. Farhadnejad H, Saber N, Neshatbini Tehrani A, et al. Herbal

products as complementary or alternative medicine for the management of hyperglycemia and dyslipidemia in patients

with type 2 diabetes: current evidence based on findings of

interventional studies. J Nutr Metab. 2024;2024:8300428.

[CrossRef]

5. Ștefănescu R, Ősz BE, Pintea A, et al. Fennel essential oil as

a complementary therapy in the management of diabetes.

Pharmaceutics. 2023;15(12):2657. [CrossRef]

6. Pain S. A potted history. Nature. 2015;525(7570):S10-S11.

[CrossRef]

7. Zuardi AW. History of cannabis as a medicine: a review. Braz

J Psychiatry. 2006;28(2):153-157. [CrossRef]

8. Azizoddin DR, Cohn AM, Ulahannan SV, et al. Cannabis use

among adults undergoing cancer treatment. Cancer.

2023;129(21):3498-3508. [CrossRef]

9. Yazici ZMC, Bilge B, Bolkent S. Anti-inflammatory potential

of delta-9-tetrahydrocannabinol in hyperinsulinemia: an

experimental study. Mol Biol Rep. 2022;49(12):11891-11899.

[CrossRef]

10. Potter DJ. The Propagation, Characterisation and Optimisation of Cannabis sativa L. as a Phytopharmaceutical. King’s

College, London; 2009.

11. Gloss D. An overview of products and bias in research. Neurotherapeutics. 2015;12(4):731-734. [CrossRef]

12. United Nations Office on Drugs and Crime. Available at:

https://www.unodc.org. Accessed March 15, 2025.

13. Erkelens JL, Hazenkamp A. That which we call Indica, by any

other name would smell as sweet. Cannabinoids. 2014;9:9-15.

14. Andre CM, Hausman JF, Guerriero G. Cannabis sativa: the

plant of the thousand and one molecules. Front Plant Sci.

2016;7:19. [CrossRef]

15. Taura F, Sirikantaramas S, Shoyama Y, Yoshikai K, Shoyama Y,

Morimoto S. Cannabidiolic-acid synthase, the chemotypedetermining enzyme in the fiber-type Cannabis sativa. FEBS

Lett. 2007;581(16):2929-2934. [CrossRef]

16. Brenneisen R. Chemistry and analysis of phytocannabinoids

and other cannabis constituents. In: ElSohly MA, ed. Marijuana and the Cannabinoids. New York: Humana Press;

2007:17-49. [CrossRef]

17. Lin YF. The endocannabinoids and potassium channels-An

updated narrative. In: Patel VB, Preedy VR, Martin CR, eds.

Neurobiology and Physiology of the Endocannabinoid System. Academis Press; 2023:107-121. [CrossRef]

18. Ross JA, Riccardelli W, Levy S. The confusing terminology of

"Medical cannabis" and cannabinoid products. J Addict Med.

2025. [CrossRef]

19. Maglaviceanu A, Peer M, Rockel J, et al. The state of synthetic

cannabinoid medications for the treatment of pain. CNS

Drugs. 2024;38(8):597-612. [CrossRef]

20. Rock EM, Parker LA. Constituents of Cannabis sativa. Adv

Exp Med Biol. 2021;1264:1-13. [CrossRef]

21. Filipiuc LE, Ababei DC, Alexa-Stratulat T, et al. Major phytocannabinoids and their related compounds: should we only

search for drugs that act on cannabinoid receptors? Pharmaceutics. 2021;13(11):1823. [CrossRef]

22. Yadav SPS, Kafle M, Ghimire NP, Shah NK, Dahal P, Pokhrel S.

An overview of phytochemical constituents and pharmacological implications of Cannabis sativa L. J Herb Med.

2023;42:100798. [CrossRef]

23. Millán-Guerrero RO, Isais-Millán S. Cannabis and the exocannabinoid and endocannabinoid systems. Their use and controversies. Gac Med Mex. 2019;155(5):471-474. [CrossRef]

24. Aloisio Caruso E, De Nunzio V, Tutino V, Notarnicola M. The

endocannabinoid system: implications in gastrointestinal

physiology and pathology. Int J Mol Sci. 2025;26(3):1306.

[CrossRef]

25. Aoki J, Isokawa M. Understanding cellular, molecular, and

functional specificity, heterogeneity, and diversity of the

endocannabinoid system. Cells. 2024;13(12):1049. [CrossRef]

26. Fonseca BM, Teixeira NA, Almada M, Taylor AH, Konje JC,

Correia-da-Silva G. Modulation of the novel cannabinoid

receptor - GPR55 - during rat fetoplacental development.

Placenta. 2011;32(6):462-469. [CrossRef]

27. Devane WA, Hanus L, Breuer A, et al. Isolation and structure

of a brain constituent that binds to the cannabinoid receptor.

Science. 1992;258(5090):1946-1949. [CrossRef]

28. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of

an endogenous 2-monoglyceride, present in canine gut, that

binds to cannabinoid receptors. Biochem Pharmacol.

1995;50(1):83-90. [CrossRef]

29. Lu Y, Anderson HD. Cannabinoid signaling in health and disease. Can J Physiol Pharmacol. 2017;95(4):311-327. [CrossRef]

30. Pertwee RG. Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications. Proc

Nutr Soc. 2014;73(1):96-105. [CrossRef]

31. Basavarajappa BS. Critical enzymes involved in endocannabinoid metabolism. Protein Pept Lett. 2007;14(3):237-246.

[CrossRef]

32. Brunetti L, Carrieri A, Piemontese L, Tortorella P, Loiodice F,

Laghezza A. Beyond the canonical endocannabinoid system.

A screening of PPAR ligands as FAAH inhibitors. Int J Mol

Sci. 2020;21(19):7026. [CrossRef]

33. Tsuboi K, Uyama T, Okamoto Y, Ueda N. N-acylethanolamines:

biological activities and metabolismEndocannabinoids and

related . Inflamm Regen. 2018;38:28. [CrossRef]

34. Kim Y, Kim W, Kim SH, et al. Cannabis sativa) root extracts

against insulin-deficient diabetes mellitus in miceProtective

effects of hemp (. Molecules. 2023;28(9):3814. [CrossRef]

35. Zhang J, Lin C, Jin S, et al. The pharmacology and therapeutic

role of cannabidiol in diabetes. Exploration (Beijing).

2023;3(5):20230047. [CrossRef]

36. Smeriglio A, Giofrè SV, Galati EM, et al. Inhibition of aldose

reductase activity by Cannabis sativa chemotypes extracts

with high content of cannabidiol or cannabigerol. Fitoterapia.

2018;127:101-108. [CrossRef]

37. Gaddy A, Elrggal M, Madariaga H, Kelly A, Lerma E, Colbert GB. Diabetic kidney disease. Dis Mon. 2025;71(4):101848.

[CrossRef]

38. Jenkin KA, McAinch AJ, Zhang Y, Kelly DJ, Hryciw DH. Elevated cannabinoid receptor 1 and G protein-coupled receptor

55 expression in proximal tubule cells and whole kidney

exposed to diabetic conditions. Clin Exp Pharmacol Physiol.

2015;42(3):256-262. [CrossRef]

39. Hryciw DH, McAinch AJ. Cannabinoid receptors in the kidney. Curr Opin Nephrol Hypertens. 2016;25(5):459-464.

[CrossRef]

40. Barutta F, Mastrocola R, Bellini S, Bruno G, Gruden G. Cannabinoid receptors in diabetic kidney disease. Curr Diab Rep.

2018;18(2):9. [CrossRef]

41. Bylan D, Khalil A, Shebaby W, et al. Lebanese cannabis oil

extract protected against folic acid-induced kidney fibrosis

in rats. PLoS One. 2024;19(12):e0311790. [CrossRef]

42. Yanar K, Coskun ZM, Beydogan AB, Aydin S, Bolkent S. The

effects of delta-9-tetrahydrocannabinol on Krüppel-like factor-4 expression, redox homeostasis, and inflammation in the

kidney of diabetic rat. J Cell Biochem. 2019;120(9):16219-

16228. [CrossRef]43. Carmona-Hidalgo B, García-Martín A, Muñoz E, GonzálezMariscal I. Detrimental effect of cannabidiol on the early

onset of diabetic nephropathy in male mice. Pharmaceuticals

(Basel). 2021;14(9):863. [CrossRef]

44. Seo H, Park SJ, Song M. Diabetic retinopathy (DR): mechanisms, current therapies, and emerging strategies. Cells.

2025;14(5):376. [CrossRef]

45. Singh R, Walia A, Kaur J, Kumar P, Verma I, Rani N. Diabetic

retinopathy - pathophysiology to treatment: a review. Curr

Diabetes Rev. 2025;21(3):58-67. [CrossRef]

46. El-Remessy AB, Al-Shabrawey M, Khalifa Y, Tsai NT, Caldwell RB, Liou GI. Neuroprotective and blood-retinal barrierpreserving effects of cannabidiol in experimental diabetes.

Am J Pathol. 2006;168(1):235-244. [CrossRef]

47. El-Remessy AB, Khalil IE, Matragoon S, et al. Neuroprotective

effect of(-)∆9-tetrahydrocannabinol and cannabidiol in

n-methyl-d-aspartate-ınduced retinal neurotoxicity:

ınvolvement of peroxynitrite. Am J Pathol. 2003;163(5):1997-

2008. [CrossRef]

48. Saraiva SM, Martín-Banderas L, Durán-Lobato M. Cannabinoid-based ocular therapies and formulations. Pharmaceutics. 2023;15(4):1077. [CrossRef]

49. Peng C, Zhang Y, Lang X, Zhang Y. Role of mitochondrial

metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis. J Transl

Med. 2023;21(1):66. [CrossRef]

50. Peng ML, Fu Y, Wu CW, Zhang Y, Ren H, Zhou SS. Signaling

pathways related to oxidative stress in diabetic cardiomyopathy. Front Endocrinol (Lausanne). 2022;13:907757.

[CrossRef]

51. Rajesh M, Mukhopadhyay P, Bátkai S, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and

inflammatory and cell death signaling pathways in diabetic

cardiomyopathy. J Am Coll Cardiol. 2010;56(25):2115-2125.

[CrossRef]

52. Vella RK, Jackson DJ, Fenning AS. 9-tetrahydrocannabinol

prevents cardiovascular dysfunction in STZ-diabetic WistarKyoto ratsΔ. BioMed Res Int. 2017;2017:7974149. [CrossRef]

53. Strand N, Anderson MA, Attanti S, et al. Diabetic neuropathy:

pathophysiology review. Curr Pain Headache Rep.

2024;28(6):481-487. [CrossRef]

54. Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):42. [CrossRef]

55. Hosseini A, Abdollahi M. Diabetic neuropathy and oxidative

stress: therapeutic perspectives. Oxid Med Cell Longev.

2013;2013:168039. [CrossRef]

56. Comelli F, Bettoni I, Colleoni M, Giagnoni G, Costa B. Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress. Phytother Res.

2009;23(12):1678-1684. [CrossRef]

57. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized

placebo-controlled double-blind clinical trial of cannabisbased medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes

Care. 2010;33(1):128-130. [CrossRef]

58. Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH.

Efficacy of inhaled cannabis on painful diabetic neuropathy.

J Pain. 2015;16(7):616-627. [CrossRef]

59. Seevathee K, Kessomboon P, Manimmanakorn N, et al. Efficacy and safety of transdermal medical cannabis

(THC:CBD:CBN formula) to treat painful diabetic peripheral

neuropathy of lower extremities. Med Cannabis Cannabinoids. 2025;8(1):1-14. [CrossRef]

60. Wallace MS, Marcotte TD, Atkinson JH, Padovano HT, BonnMiller M. A secondary analysis from a randomized trial on the

effect of plasma tetrahydrocannabinol levels on pain reduction in painful diabetic peripheral neuropathy. J Pain.

2020;21(11-12):1175-1186. [CrossRef]

61. Jesus CHA, Redivo DDB, Gasparin AT, et al. Cannabidiol

attenuates mechanical allodynia in streptozotocin-induced

diabetic rats via serotonergic system activation through

5-HT1A receptors. Brain Res. 2019;1715:156-164. [CrossRef]

62. Khan I, Kaur S, Rishi AK, Boire B, Aare M, Singh M. Cannabidiol

and beta-caryophyllene combination attenuates diabetic

neuropathy by ınhibiting NLRP3 inflammasome/NFκB

through the AMPK/sirT3/Nrf2 axis. Biomedicines.

2024;12(7):1442. [CrossRef]

63. Türkiye uyuşturucu raporu 2024. Available at: https://www.

narkotik.pol.tr/kurumlar/icisleri.gov.tr/duyurular(1)/2024_u

yus_raporu.pdf. Accessed May 12, 2025.

64. Kenevir Yetiştiriciliği Ve Kontrolü Hakkında Yönetmelik. Available at: https://resmigazete.gov.tr/eskiler/2016/09/20160

929-3.htm. Accessed May 12, 2025.

65. Uyuşturucu Maddelerin Murakabesi Hakkında Kanun. Available at: https://www.mevzuat.gov.tr/MevzuatMetin/1.3.2313

.pdf. Accessed May 12, 2025.