The Role of Cannabidiol (CBD) in Chronic Pain Management: An Assessment of Current Evidence

Purpose of Review

Given the growing challenges in chronic pain management coupled with the ongoing consequences of the opioid epidemic, pain management practitioners are looking into more effective, innovative, and safer alternatives to treat pain. Cannabis-based medicine had been described for hundreds of years but only recently have we seen the more scientific, evidence-based approach to its use, and ongoing investigations continue to explore its potential medical benefits. While historically more attention has been paid to the psychoactive component of the cannabis plant Δ9-tetrahydrocannabinol (THC), there have been fewer scientific studies on the medical use of the cannabidiol (CBD) – a non-psychoactive component of the cannabis plant.

Recent Findings

By examining recent literature, we investigated the use of CBD and its potential role in pain management. Since there are currently no approved pharmaceutical products that contain CBD alone for the management of pain, this review focused on nabiximols (which is a combined product of THC/CBD in a 1:1 ratio) as the only pharmaceutical product available that contains CBD and is being used for the management of pain. It is difficult to definitely attribute the therapeutic properties to CBD alone since it is always administered with THC. Based on the available literature, it is difficult to make a recommendation for the use of CBD in chronic pain management. It is also important to note that there are many CBD products currently available as supplements, but these products are non-pharmaceuticals and lack the appropriate clinical studies to support their efficacy claims.

This is a preview of subscription content, log in to check access.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.

    •• Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180–8 (excellent review on Cannabinoids focused on pharmacology).

    PubMed PubMed Central Google Scholar 

  2. 2.

    •• Vučković S, Srebro D, Vujović KS, Vučetić Č, Prostran M. Cannabinoids and Pain: New Insights From Old Molecules. Front Pharmacol. 2018;9:1259 (excellent review on Cannabinoids and Pain).

    Article Google Scholar 

  3. 3.

    Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245–59.

    CAS Article Google Scholar 

  4. 4.

    Costa B, Trovato AE, 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(1–3):75–83.

    CAS Article Google Scholar 

  5. 5.

    Kumar RN, Chambers WA, Pertwee RG. Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anaesthesia. 2001;56(11):1059–68.

    CAS Article Google Scholar 

  6. 6.

    Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58(3):389–462.

    CAS Article Google Scholar 

  7. 7.

    Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018;19(3):833 Published 2018 Mar 13.

    Article Google Scholar 

  8. 8.

    Anand P, Whiteside G, Fowler CJ, Hohmann AG. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev. 2009;60(1):255–66.

    CAS Article Google Scholar 

  9. 9.

    Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015;172(20):4790–805.

    CAS Article Google Scholar 

  10. 10.

    Hammell DC, Zhang LP, Ma F, , Abshire SM, McIlwrath S, Stinchcomb AL, Westlund KNet al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936–948.

    CAS Article Google Scholar 

  11. 11.

    Philpott HT, OʼBrien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017;158(12):2442–51.

    CAS Article Google Scholar 

  12. 12.

    Malfait AM, Gallily R, Sumariwalla PF, , Malik AS, Andreakos E, Mechoulam R, Feldmann Met al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 2000;97(17):9561–9566.

    CAS Article Google Scholar 

  13. 13.

    Babalonis S, Haney M, Malcolm RJ, , Lofwall MR, Votaw VR, Sparenborg S, Walsh SLet al. Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers. Drug Alcohol Depend. 2017;172:9–13.

    CAS Article Google Scholar 

  14. 14.

    Sekar K, Pack A. Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. F1000Res. 2019;8:F1000 Faculty Rev-234.

    Article Google Scholar 

  15. 15.

    Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses. 2006;66(2):234–46.

    CAS Article Google Scholar 

  16. 16.

    Vermersch P, Trojano M. Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice. Eur Neurol. 2016;76(5–6):216–26. https://doi.org/10.1159/000449413.

    CAS Article PubMed Google Scholar 

  17. 17.

    Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, et al. The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews. Curr Neurol Neurosci Rep. 2018;18(2):8.

    Article Google Scholar 

  18. 18.

    Ferrè L, Nuara A, Pavan G, Radaelli M, Moiola L, Rodegher M, et al. Efficacy and safety of nabiximols (Sativex(®)) on multiple sclerosis spasticity in a real-life Italian monocentric study. Neurol Sci. 2016;37(2):235–42.

    Article Google Scholar 

  19. 19.

    Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage. 2013;46(2):207–18.

    Article Google Scholar 

  20. 20.

    Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13(5):438–49.

    CAS Article Google Scholar 

  21. 21.

    •• Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, et al. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain. J Pain Symptom Manage. 2018;55(2):179–188.e1 (excellent study on Cannabinoids and Cancer Pain).

    Article Google Scholar 

  22. 22.

    Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133(1–3):210–20.

    CAS Article Google Scholar 

  23. 23.

    Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006;45(1):50–2.

    CAS Article Google Scholar 

  24. 24.

    Cannabinoid Buccal Spray for Chronic Non-Cancer or Neuropathic Pain: A Review of Clinical Effectiveness, Safety, and Guidelines. 2016 Sep 21;. Review.

  25. 25.

    Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res. Manag. 19:328–35.

    Article Google Scholar 

  26. 26.

    Darkovska-Serafimovska M, Serafimovska T, Arsova-Sarafinovska Z, Stefanoski S, Keskovski Z, Balkanov T. Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases. J Pain Res. 2018;11:837–42.

    Article Google Scholar 

  27. 27.

    The FDA Warning Letters and Test Results for Cannabidiol-Related Products. https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products.

Download references

Author information

Affiliations

Corresponding author

Correspondence to Richard D. Urman.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Other Pain

 

 


Older Post