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Abstract

Objectives

To examine the tolerability and effectiveness of medicinal cannabis prescribed to patients for chronic, refractory pain, with a subset analysis on arthritis.

Methods

This was an interim analysis of the CA Clinics Observational Study investigating self-reported adverse events (AEs) and changes in health-related quality of life (HRQoL) outcomes over time after commencing medicinal cannabis. Patients were prescribed medicinal cannabis by a medical practitioner, containing various ratios of Δ⁹-tetrahydrocannabinol (THC) and/or cannabidiol (CBD).

Results

The overall chronic pain cohort, and specifically the balanced CBD:THC products, were associated with significantly reduced pain intensity scores (p = 0.003, p = 0.025), with 22% of patients reporting a clinically meaningful reduction in pain intensity. Patients in the arthritis subset (n = 199) reported significantly reduced pain intensity scores (p = 0.005) overall, and specifically for those taking CBD-only (p = 0.018) and balanced products (p = 0.005). Other HRQoL outcomes, including pain interference and pain impact scores were significantly improved depending on the CBD:THC ratio. Products that contained a balanced ratio of CBD:THC were associated with improvements in the most number of PROMIS-29 domains. Approximately half (n = 364; 51%) of the chronic pain cohort experienced at least one AE, the most common being dry mouth (24%), somnolence (19%) or fatigue (12%). These findings were similar in the arthritis subset.

Discussion

Medicinal cannabis was observed to improve pain intensity scores and HRQoL outcomes in patients with chronic, refractory pain, providing real-world insights into medicinal cannabis’ therapeutic potential.

Keywords

Medicinal cannabis cannabidiol chronic pain arthritis observational study

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References

Treede

R-D

Rief

Barke

, et al. A classification of chronic pain for ICD-11. Pain 2015; 156: 1003–1007. DOI: 10.1097/j.pain.0000000000000160.

Katz

Arant

Loeser

. Diagnosis and treatment of hip and knee osteoarthritis: A review. JAMA 2021; 325: 568–578. DOI: 10.1001/jama.2020.22171.

Hogg

Kavanagh

Farrell

, et al. Waiting in pain II: an updated review of the provision of persistent pain services in Australia. Pain Med 2020; 22: 1367–1375. DOI: 10.1093/pm/pnaa374.

Blyth

March

Brnabic

, et al. Chronic pain in Australia: a prevalence study. Pain 2001; 89: 127–134. DOI: 10.1016/s0304-3959(00)00355-9.

Phillips

. The cost and burden of chronic pain. Rev Pain 2009; 3: 2–5. DOI: 10.1177/204946370900300102.

Hylands-White

Duarte

Raphael

. An overview of treatment approaches for chronic pain management. Rheumatol Int 2017; 37: 29–42. DOI: 10.1007/s00296-016-3481-8.

Krebs

Gravely

Nugent

, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the space randomized clinical trial. JAMA 2018; 319: 872–882. DOI: 10.1001/jama.2018.0899.

Dowell

Haegerich

Chou

. CDC guideline for prescribing ppioids for chronic pain - United States, 2016. Morb Mortal Wkly Rep 2016; 65: 1–49. DOI: 10.15585/mmwr.rr6501e1.

Johal

Devji

Chang

, et al. Cannabinoids in chronic non-cancer Pain: a systematic review and meta-analysis. Clin Med Insights Arthritis Musculoskelet Disord 2020; 13: 117954412090646. DOI: 10.1177/1179544120906461.

10.

Aviram

Pud

Gershoni

, et al. Medical cannabis treatment for chronic pain: outcomes and prediction of response. Eur J Pain 2020: 25: 1532–2149. DOI: 10.1002/ejp.1675.

11.

Costa

. Pain. In: Pertwee

(ed) Handbook of Cannabis. Oxford: Oxford University Press, 2014.

12.

Di Marzo

Melck

Bisogno

, et al. Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 1998; 21: 521–528. DOI: 10.1016/S0166-2236(98)01283-1.

13.

Howlett

Barth

Bonner

, et al. International union of pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002; 54: 161–202. DOI: 10.1124/pr.54.2.161.

14.

Cabral

Staab

. Effects on the immune system. Handbook Exp Pharmacol 2005; 168: 385–423. DOI: 10.1007/3-540-26573-2_13.

15.

Pertwee

. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997; 74: 129–180. DOI: 10.1016/s0163-7258(97)82001-3.

16.

DeLong

Wolf

Poklis

, et al. Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol. Drug and Alcohol Dependence 2010; 112: 126–133. DOI: 10.1016/j.drugalcdep.2010.05.019.

17.

Izzo

Borrelli

Capasso

, et al. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009; 30: 515–527. DOI: 10.1016/j.tips.2009.07.006.

18.

Mechoulam

Peters

Murillo-Rodriguez

, et al. Cannabidiol – recent advances. Chem Biodivers 2007; 4: 1678–1692. DOI: 10.1002/cbdv.200790147.

19.

Nichols

Kaplan

BLF

. Immune responses regulated by cannabidiol. Cannabis Cannabinoid Res 2020; 5: 12–31. DOI: 10.1089/can.2018.0073.

20.

Freckelton

. Medicinal cannabis law reform in Australia. J L Med 2016; 23: 497–515

21.

(TGA) TGA . Access to medicinal cannabis products, 2020, https://www.tga.gov.au/node/769199 (accessed 10 08 2020).

22.

Brown

Wood

. The medical dictionary for regulatory activities (MedDRA). Drug Safety 1999; 20: 109–117. DOI: 10.2165/00002018-199920020-00002.

23.

Hays

Spritzer

Schalet

, et al. PROMIS®-29 v2. 0 profile physical and mental health summary scores. Qual Life Res 2018; 27: 1885–1891.

24.

Rose

Bayliss

Huang

, et al. Evaluating the PROMIS-29 v2.0 for use among older adults with multiple chronic conditions. Qual Life Res Int J Qual Life Aspects Treat Care Rehabil 2018; 27: 2935–2944. DOI: 10.1007/s11136-018-1958-5.

25.

Deyo

Ramsey

Buckley

, et al. Performance of a patient reported outcomes measurement information system (PROMIS) short form in older adults with chronic musculoskeletal pain. Pain Med 2016; 17: 314–324.

26.

Hays

Spritzer

Fries

, et al. Responsiveness and minimally important difference for the patient-reported outcomes measurement information system (PROMIS) 20-item physical functioning short form in a prospective observational study of rheumatoid arthritis. Ann Rheum Dis 2015; 74: 104–107. DOI: 10.1136/annrheumdis-2013-204053.

27.

Kroenke

, et al. Operating characteristics of PROMIS four-item depression and anxiety scales in primary care patients with chronic pain. Pain Med 2014; 15: 1892–1901. DOI: 10.1111/pme.12537.

28.

Yost

Eton

Garcia

, et al. Minimally important differences were estimated for six patient-reported outcomes measurement information system-cancer scales in advanced-stage cancer patients. J Clin Epidemiol 2011; 64: 507–516. DOI: 10.1016/j.jclinepi.2010.11.018.

29.

Whiting

Wolff

Deshpande

, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015; 313: 2456–2473. DOI: 10.1001/jama.2015.6358.

30.

Kalso

Edwards

Moore

, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004; 112: 372–380. DOI: 10.1016/j.pain.2004.09.019.

31.

Malfait

Gallily

Sumariwalla

, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 2000; 97: 9561–9566. DOI: 10.1073/pnas.160105897.

32.

Hobbs

Vazquez

Remijan

, et al. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res 2020; 34: 1696–1703. DOI: 10.1002/ptr.6651.

33.

Capano

Weaver

Burkman

. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgrad Med J 2020; 132: 56–61. DOI: 10.1080/00325481.2019.1685298.

34.

Arnold

. A primer on medicinal cannabis safety and potential adverse effects. Aust J Gen Pract 2021; 50: 345–350. DOI: 10.31128/AJGP-02-21-5845.

35.

Überall

. A review of scientific evidence for THC:CBD oromucosal spray (Nabiximols) in the management of chronic pain. J Pain Res 2020; 13: 399–410. DOI: 10.2147/jpr.S240011.

36.

Fisher

Moore

Fogarty

, et al. Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Pain 2021; 162: S45–s66. DOI: 10.1097/j.pain.0000000000001929.

37.

Henderson

Kotsirilos

Cairns

, et al. Medicinal cannabis in the treatment of chronic pain. Aust J Gen Pract 2021; 50: 724–732.

38.

Ueberall

Essner

Mueller-Schwefe

. Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-registry. J Pain Res 2019; 12: 1577–1604. DOI: 10.2147/JPR.S192174.

39.

Johnson

Burnell-Nugent

Lossignol

, et al. Multicenter, double blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage 2010; 39: 167–179. DOI: 10.1016/j.jpainsymman.2009.06.008.

40.

van de Donk

Niesters

Kowal

, et al. An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain 2019; 160: 860–869. DOI: 10.1097/j.pain.0000000000001464.

41.

Berman

Symonds

Birch

. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain 2004; 112: 299–306. DOI: 10.1016/j.pain.2004.09.013.

42.

Sokolove

Lepus

. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis 2013; 5: 77–94. DOI: 10.1177/1759720X12467868.

43.

Pisetsky

Ward

. Advances in the treatment of inflammatory arthritis. Best Pract Res Clin Rheumatol 2012; 26: 251–261. DOI: 10.1016/j.berh.2012.03.001.

44.

Sherman

Anderson

Dal Pan

, et al.

Real-world evidence - what is it and what can it tell us?

N Engl J Med 2016; 375: 2293–2297. DOI: 10.1056/NEJMsb1609216.

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Medicinal cannabis for Australian patients with chronic refractory pain including arthritis