Enhancing Cannabinoid Bioavailability in Pain Management: The Role of Cyclodextrins

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2024 Nov 27

PMID 39598730

Authors

Adriana Ribeiro

Rui Loureiro

Helena Cabral-Marques

Affiliations

Soon will be listed here.

Abstract

Chronic pain (CP), including pain related to cancer, affects approximately 2 billion people worldwide, significantly diminishing quality of life and imposing socio-economic burdens. Current treatments often provide limited relief and may cause adverse effects, demanding more effective alternatives. Natural compounds from L., particularly cannabinoids like THC and CBD, exhibit analgesic and anti-inflammatory properties, but their therapeutic use is restricted by poor solubility and low bioavailability. Cyclodextrins (CDs) and cyclic oligosaccharides may encapsulate hydrophobic drugs in order to enhance their solubility and stability, offering a promising solution to these challenges. This study explores the formation of CD inclusion complexes with cannabinoids and specific terpenes, such as D-limonene (LIM), beta-caryophyllene (BCP), and gamma-terpinene (γ-TPN), aiming to improve pharmacokinetic profiles and therapeutic efficacy. We discuss analytical techniques for characterizing these complexes and their mechanisms of action, highlighting the potential of CDs to optimize drug formulations. The integration of CDs in cannabinoid therapies may enhance patient compliance and treatment outcomes in CP management. Future research should focus on innovative formulations and delivery systems to maximize the clinical applications of those compounds.

Citing Articles

Curcumin in Ophthalmology: Mechanisms, Challenges, and Emerging Opportunities.

Ribeiro A, Oliveira D, Cabral-Marques H Molecules. 2025; 30(3).

PMID: 39942561 PMC: 11820683. DOI: 10.3390/molecules30030457.

References

Hamilton D, Ernst C, Kramer W, Madden D, Lang E, Liao E . Pharmacokinetics of Diclofenac and Hydroxypropyl-β-Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD-Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment. Clin Pharmacol Drug Dev. 2017; 7(2):110-122. PMC: 5814843. DOI: 10.1002/cpdd.417. View

Cid-Samamed A, Rakmai J, Mejuto J, Simal-Gandara J, Astray G . Cyclodextrins inclusion complex: Preparation methods, analytical techniques and food industry applications. Food Chem. 2022; 384:132467. DOI: 10.1016/j.foodchem.2022.132467. View

Quintans-Junior L, Araujo A, Brito R, Santos P, S S Quintans J, Menezes P . β-caryophyllene, a dietary cannabinoid, complexed with β-cyclodextrin produced anti-hyperalgesic effect involving the inhibition of Fos expression in superficial dorsal horn. Life Sci. 2016; 149:34-41. DOI: 10.1016/j.lfs.2016.02.049. View

Mannila J, Jarvinen T, Jarvinen K, Tarvainen M, Jarho P . Effects of RM-beta-CD on sublingual bioavailability of Delta9-tetrahydrocannabinol in rabbits. Eur J Pharm Sci. 2005; 26(1):71-7. DOI: 10.1016/j.ejps.2005.04.020. View

Waleczek K, Cabral Marques H, Hempel B, Schmidt P . Phase solubility studies of pure (-)-alpha-bisabolol and camomile essential oil with beta-cyclodextrin. Eur J Pharm Biopharm. 2003; 55(2):247-51. DOI: 10.1016/s0939-6411(02)00166-2. View

Saokham P, Muankaew C, Jansook P, Loftsson T . Solubility of Cyclodextrins and Drug/Cyclodextrin Complexes. Molecules. 2018; 23(5). PMC: 6099580. DOI: 10.3390/molecules23051161. View

Antunes F, Pereira R, Afonso V, Tinoco R . Prevalence and Characteristics of Chronic Pain Among Patients in Portuguese Primary Care Units. Pain Ther. 2021; 10(2):1427-1437. PMC: 8586319. DOI: 10.1007/s40122-021-00308-2. View

Pina L, Rabelo T, Borges L, S S Goncalves V, Silva A, Oliveira M . Antihyperalgesic effect of γ-terpinene complexed in β-cyclodextrin on neuropathic pain model induced by tumor cells. Int J Pharm. 2024; 662:124538. DOI: 10.1016/j.ijpharm.2024.124538. View

Shinde U, Joshi P, Jain D, Singh K . Preparation and Evaluation of N-Trimethyl Chitosan Nanoparticles of Flurbiprofen for Ocular Delivery. Curr Eye Res. 2019; 44(5):575-582. DOI: 10.1080/02713683.2019.1567793. View

10.

Benet L, Hosey C, Ursu O, Oprea T . BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev. 2016; 101:89-98. PMC: 4910824. DOI: 10.1016/j.addr.2016.05.007. View

11.

Hossain K, Alghalayini A, Valenzuela S . Current Challenges and Opportunities for Improved Cannabidiol Solubility. Int J Mol Sci. 2023; 24(19). PMC: 10572536. DOI: 10.3390/ijms241914514. View

12.

Shahbazi F, Grandi V, Banerjee A, Trant J . Cannabinoids and Cannabinoid Receptors: The Story so Far. iScience. 2020; 23(7):101301. PMC: 7339067. DOI: 10.1016/j.isci.2020.101301. View

13.

Wupper S, Luersen K, Rimbach G . Cyclodextrins, Natural Compounds, and Plant Bioactives-A Nutritional Perspective. Biomolecules. 2021; 11(3). PMC: 7998733. DOI: 10.3390/biom11030401. View

14.

Santos P, Oliveira T, R Junior L, Figueiras A, Nunes L . β-caryophyllene Delivery Systems: Enhancing the Oral Pharmacokinetic and Stability. Curr Pharm Des. 2018; 24(29):3440-3453. DOI: 10.2174/1381612824666180912151412. View

15.

Davis M, Brewster M . Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004; 3(12):1023-35. DOI: 10.1038/nrd1576. View

16.

Elikkottil J, Elikottil J, Gupta P, Gupta K . The analgesic potential of cannabinoids. J Opioid Manag. 2010; 5(6):341-57. PMC: 3728280. View

17.

De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini P, Orlando P . Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther. 2008; 325(3):1007-15. DOI: 10.1124/jpet.107.134809. View

18.

Park J, Roh J, Pan J, Kim Y, Park C, Jo Y . Role of Resolvins in Inflammatory and Neuropathic Pain. Pharmaceuticals (Basel). 2023; 16(10). PMC: 10610411. DOI: 10.3390/ph16101366. View

19.

Loftsson T, Duchene D . Cyclodextrins and their pharmaceutical applications. Int J Pharm. 2006; 329(1-2):1-11. DOI: 10.1016/j.ijpharm.2006.10.044. View

20.

Crini G . Review: a history of cyclodextrins. Chem Rev. 2014; 114(21):10940-75. DOI: 10.1021/cr500081p. View