CANNABINOIDS IN CHRONIC PAIN MANAGEMENT: EFFICACY, SAFETY, AND THE CONTROVERSIES SURROUNDING MEDICAL MARIJUANA – A REVIEW OF CURRENT EVIDENCE

Keywords: Cannabidiol, Chronic Pain Management, Tetrahydrocannabinol, Cannabis

Abstract

Chronic pain is a highly complex phenomenon in terms of both etiology and clinical presentation. Due to its prolonged duration, it significantly impairs the functioning of many patients. In the era of modern analgesic therapy, increasing hope is placed on the use of cannabis-based preparations. Cannabinoids, primarily THC and CBD, acting on the endocannabinoid system, exhibit analgesic, anti-inflammatory, and even neuroprotective effects. They have a relatively favorable safety profile for patients, and their adverse effects typically do not interfere with patients' daily functioning. However, due to the variable efficacy reported in previous studies, the potential placebo effect, and short-term observations, a larger number of well-designed, double-blind randomized controlled trials are required to precisely determine the role of cannabinoids in chronic pain management.

References

Kang Y, Trewern L, Jackman J, McCartney D, Soni A. Chronic pain: definitions and diagnosis. BMJ. 2023;381:e076036. Published 2023 Jun 27. doi:10.1136/bmj-2023-076036

Dahlhamer JM, Connor EM, Bose J, Lucas JL, Zelaya CE. Prescription Opioid Use Among Adults With Chronic Pain: United States, 2019. Natl Health Stat Report. 2021;(162):1-9.

Charitos IA, Gagliano-Candela R, Santacroce L, Bottalico L. The Cannabis Spread throughout the Continents and its Therapeutic Use in History. Endocr Metab Immune Disord Drug Targets. 2021;21(3):407-417. doi:10.2174/1871530320666200520095900

Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-847. doi:10.18433/j3vw2f

Juurlink, David N., and Irfan A. Dhalla. "Dependence and addiction during chronic opioid therapy." Journal of Medical Toxicology 8 (2012): 393-399.

Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol. 2011;106(5):835-843. doi:10.1038/ajg.2011.30

Hill R, Santhakumar R, Dewey W, Kelly E, Henderson G. Fentanyl depression of respiration: Comparison with heroin and morphine. Br J Pharmacol. 2020;177(2):254-266. doi:10.1111/bph.14860

Peyravian, Nadia, et al. "The anti-inflammatory effects of cannabidiol (CBD) on acne." Journal of inflammation research (2022): 2795-2801.

Atalay, Sinemyiz, Iwona Jarocka-Karpowicz, and Elzbieta Skrzydlewska. "Antioxidative and anti-inflammatory properties of cannabidiol." Antioxidants 9.1 (2019): 21.

Głodowska, Martyna, and Malgorzata Łyszcz. "11. Cannabis sativa L. and its antimicrobial properties–A review." (2017).

Borgonetti, Vittoria, et al. "Investigation on the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract in an in vitro model of excitotoxicity." Fitoterapia 163 (2022): 105315.

Kim, Yujeong, et al. "Protective effects of hemp (Cannabis sativa) root extracts against insulin-deficient diabetes mellitus in mice." Molecules 28.9 (2023): 3814.

Longo R, Oudshoorn A, Befus D. Cannabis for Chronic Pain: A Rapid Systematic Review of Randomized Control Trials. Pain Manag Nurs. 2021;22(2):141-149. doi:10.1016/j.pmn.2020.11.006

McDonagh MS, Morasco BJ, Wagner J, et al. Cannabis-Based Products for Chronic Pain : A Systematic Review. Ann Intern Med. 2022;175(8):1143-1153. doi:10.7326/M21-4520

Hua T, Li X, Wu L, et al. Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures. Cell. 2020;180(4):655-665.e18. doi:10.1016/j.cell.2020.01.008

Oyagawa CRM, Grimsey NL. Cannabinoid receptor CB1 and CB2 interacting proteins: Techniques, progress and perspectives. Methods Cell Biol. 2021;166:83-132. doi:10.1016/bs.mcb.2021.06.011

Callén L, Moreno E, Barroso-Chinea P, et al. Cannabinoid receptors CB1 and CB2 form functional heteromers in brain. J Biol Chem. 2012;287(25):20851-20865. doi:10.1074/jbc.M111.335273

Mackie, Ken. "Cannabinoid receptors: where they are and what they do." Journal of neuroendocrinology 20 (2008): 10-14.

Aizpurua-Olaizola, Oier, et al. "Targeting the endocannabinoid system: future therapeutic strategies." Drug discovery today 22.1 (2017): 105-110.

Russo EB, Marcu J. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Adv Pharmacol. 2017;80:67-134. doi:10.1016/bs.apha.2017.03.004

Pintori N, Caria F, De Luca MA, Miliano C. THC and CBD: Villain versus Hero? Insights into Adolescent Exposure. Int J Mol Sci. 2023;24(6):5251. Published 2023 Mar 9. doi:10.3390/ijms24065251

Chayasirisobhon S. Mechanisms of Action and Pharmacokinetics of Cannabis. Perm J. 2020;25:1-3. doi:10.7812/TPP/19.200

Oliver D, Englund A, Chesney E, et al. Cannabidiol does not attenuate acute delta-9-tetrahydrocannabinol-induced attentional bias in healthy volunteers: A randomised, double-blind, cross-over study. Addiction. 2024;119(2):322-333. doi:10.1111/add.16353

Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology (Berl). 2021;238(1):9-28. doi:10.1007/s00213-020-05712-8

Kolli AR, Hoeng J. Cannabidiol Bioavailability Is Nonmonotonic with a Long Terminal Elimination Half-Life: A Pharmacokinetic Modeling-Based Analysis. Cannabis Cannabinoid Res. 2025;10(1):81-91. doi:10.1089/can.2023.0214

Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020. doi:10.1056/NEJMoa1611618

Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011;72(5):735-744. doi:10.1111/j.1365-2125.2011.03970.x

Aviram J, Samuelly-Leichtag G. Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Physician. 2017;20(6):E755-E796.

Hauser W, Fitzcharles MA. The Perils of Overestimating the Efficacy of Cannabis-Based Medicines for Chronic Pain Management. Pain Physician. 2018;21(1):E79-E80.

Barakji J, Korang SK, Feinberg J, et al. Cannabinoids versus placebo for pain: A systematic review with meta-analysis and Trial Sequential Analysis. PLoS One. 2023;18(1):e0267420. Published 2023 Jan 30. doi:10.1371/journal.pone.0267420

Horsted T, Hesthaven KL, Leutscher PDC. Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study. Eur J Pain. 2023;27(2):234-247. doi:10.1002/ejp.2054

Johal H, Devji T, Chang Y, Simone J, Vannabouathong C, Bhandari M. Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis. Clin Med Insights Arthritis Musculoskelet Disord. 2020;13:1179544120906461. Published 2020 Feb 19. doi:10.1177/1179544120906461

Chandy M, Nishiga M, Wei TT, Hamburg NM, Nadeau K, Wu JC. Adverse Impact of Cannabis on Human Health. Annu Rev Med. 2024;75:353-367. doi:10.1146/annurev-med-052422-020627

Velayudhan L, Pisani S, Dugonjic M, McGoohan K, Bhattacharyya S. Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference. Age Ageing. 2024;53(11):afae261. doi:10.1093/ageing/afae261

Kawka M, Erridge S, Holvey C, et al. Clinical Outcome Data of First Cohort of Chronic Pain Patients Treated With Cannabis-Based Sublingual Oils in the United Kingdom: Analysis From the UK Medical Cannabis Registry. J Clin Pharmacol. 2021;61(12):1545-1554. doi:10.1002/jcph.1961

Chesney E, Oliver D, Green A, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology. 2020;45(11):1799-1806. doi:10.1038/s41386-020-0667-2

Schoedel KA, Szeto I, Setnik B, et al. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial. Epilepsy Behav. 2018;88:162-171. doi:10.1016/j.yebeh.2018.07.027

Pertwee RG. Cannabinoids and the gastrointestinal tract. Gut. 2001;48(6):859-867. doi:10.1136/gut.48.6.859

Morgan CJ, Freeman TP, Schafer GL, Curran HV. Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology. 2010;35(9):1879-1885. doi:10.1038/npp.2010.58

Curioni C, André C. Rimonabant for overweight or obesity. Cochrane Database Syst Rev. 2006;2006(4):CD006162. Published 2006 Oct 18. doi:10.1002/14651858.CD006162.pub2

Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019;124(1):28-31. doi:10.1111/bcpt.13152

Smythe MA, Wu W, Garwood CL. Anticoagulant drug-drug interactions with cannabinoids: A systematic review. Pharmacotherapy. 2023;43(12):1327-1338. doi:10.1002/phar.2881

Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. Published 2023 Feb 8. doi:10.1159/000528465

Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58(9):1586-1592. doi:10.1111/epi.13852

Ho JJY, Goh C, Leong CSA, Ng KY, Bakhtiar A. Evaluation of potential drug-drug interactions with medical cannabis. Clin Transl Sci. 2024;17(5):e13812. doi:10.1111/cts.13812

Critchley, David, et al. "Drug-drug interaction studies with coadministration of cannabidiol (CBD) and clobazam, valproate, stiripentol or midazolam in healthy volunteers and adults with epilepsy." Epilepsy & Behavior 101 (2019).

Benowitz NL, Jones RT. Effects of delta-9-tetrahydrocannabinol on drug distribution and metabolism. Antipyrine, pentobarbital, and ethanol. Clin Pharmacol Ther. 1977;22(3):259-268. doi:10.1002/cpt1977223259

Vierke C, Marxen B, Boettcher M, Hiemke C, Havemann-Reinecke U. Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy. Eur Arch Psychiatry Clin Neurosci. 2021;271(5):847-856. doi:10.1007/s00406-019-01091-0

Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90(6):844-851. doi:10.1038/clpt.2011.188

Manini AF, Yiannoulos G, Bergamaschi MM, et al. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. J Addict Med. 2015;9(3):204-210. doi:10.1097/ADM.0000000000000118

Schulze Westhoff M, Massarou C, Bleich S, et al. Drug interactions in a sample of inpatients diagnosed with cannabis use disorder. J Neural Transm (Vienna). 2025;132(5):723-730. doi:10.1007/s00702-025-02884-5

Christo PJ, Vortsman E, Gharibo C, LeQuang JAK, Pergolizzi JV. Considering Long-Acting Synthetic Cannabidiol for Chronic Pain: A Narrative Review. Cureus. 2025;17(4):e81577. Published 2025 Apr 1. doi:10.7759/cureus.81577

Published
2025-12-30
Citations
How to Cite
Szymon Szabelski, Adam Solarz, Joanna Kryślak, Maciej Sokołowski, & Karolina Oskroba. (2025). CANNABINOIDS IN CHRONIC PAIN MANAGEMENT: EFFICACY, SAFETY, AND THE CONTROVERSIES SURROUNDING MEDICAL MARIJUANA – A REVIEW OF CURRENT EVIDENCE. International Journal of Innovative Technologies in Social Science, 3(4(48). https://doi.org/10.31435/ijitss.4(48).2025.4212

Most read articles by the same author(s)