Table Info

Table 3.

Mean difference and 95% CI Bonferroni-adjusted for multiple comparisons from pairwise comparisons for all outcomes measures

Pairwise comparisons (mean differences, CI)^a	Pain mechanism						Baseline cannabinoid profile			Visit
Pairwise comparisons (mean differences, CI)^a	Neuropathic vs. nociceptive	Neuropathic vs. mixed^b	Neuropathic vs. undefined^b	Nociceptive vs. mixed^b	*Nociceptive vs.* undefined^b**	*Mixed vs.* undefined^b**	*CBD-dominant vs.* THC:CBD**	*CBD-dominant vs.* THC-dominant^c**	*THC:CBD vs.* THC-dominant^c**	*Baseline vs.* FUP3M**
BPI-SF pain severity	0.49 (0.15; 0.82)^*	–0.06 (–0.57; 0.44)	0.24 (–0.6; 1.08)	–0.55 (–1.06; –0.04)	–0.25 (–1.09; 0.59)	0.30 (–0.62; 1.23)	–0.33 (–0.61; –0.05)	–0.24 (–2.44; 1.97)	0.09 (–2.11; 2.30)	0.79 (0.56; 1.02)^*
BPI-SF pain-related interference	0.44 (0.04; 0.84)	0.05 (–0.55; 0.65)	0.07 (–0.93; 1.07)	–0.39 (–1.00; 0.21)	–0.37 (–1.37; 0.63)	0.03 (–1.07; 1.12)	0.42 (–0.75; –0.09)^*	–0.55 (–3.17; 2.07)	–0.13 (–2.75; 2.49)	1.46 (1.19; 1.73)^*
ESAS-r pain	0.43 (0.06; 0.81)^*	–0.23 (–0.80; 0.33)	0.15 (–0.79; 1.10)	–0.67 (–1.24; –0.10)^*	–0.28 (–1.22; 0.67)	0.39 (–0.65; 1.43)	–0.29 (–0.61; 0.02)	–0.27 (–2.75; 2.20)	0.02 (–2.45; 2.49)	1.02 (0.76; 1.27)^*
ESAS-r anxiety	0.30 (–0.25; 0.86)	0.31 (–0.54; 1.15)	–0.30 (–1.70; 1.09)	0.00 (–0.85; 0.85)	–0.61 (–2.01; 0.79)	–0.61 (–2.15; 0.93)	–0.49 (–0.96; –0.03)	0.99 (–2.67; 4.66)	1.48 (–2.18; 5.15)	0.70 (0.32; 1.08)^*
ESAS-r depression	0.27 (–0.25; 0.79)	0.05 (–0.55; 0.65)	0.36 (–0.96; 1.69)	–0.21 (–1.01; 0.58)	0.1 (–1.23; 1.43)	0.31 (–1.14; 1.76)	–0.56 (–1.00; –0.12)^*	0.02 (–3.41; 3.45)	0.58 (–2.85; 4.01)	0.62 (0.26; 0.98)^*
ESAS-r fatigue	0.79 (0.33; 1.25)^*	0.01 (–0.68; 0.70)	0.07 (–1.08; 1.22)	–0.78 (–1.48; –0.08)^*	–0.72 (–1.87; 0.43)	0.06 (–1.2; 1.33)	–0.17 (–0.56; 0.21)	2.38 (–0.64; 5.40)	2.55 (–0.46; 5.57)	0.93 (0.61; 1.24)^*
ESAS-r drowsiness	0.77 (0.22; 1.31)^*	0.66 (–0.16; 1.49)	0.10 (–1.19; 1.57)	–0.10 (–0.93; 0.72)	–0.57 (–1.96; 0.81)	–0.47 (–1.98; 1.04)	–0.21 (–0.67; 0.24)	2.29 (–1.28; 5.86)	2.50 (–1.07; 6.073)	0.69 (0.32; 1.06)^*
ESAS-r sleep	1.71 (–1.01; 4.43)	0.40 (–1.67; 2.46)	–0.74 (–3.1; 1.61)	–1.32 (–3.38; 0.75)	–2.46 (–4.81; –0.10)	–1.14 (–2.69; 0.41)	–0.45 (–1.20; 0.30)	1.71 (–1.99; 5.42)	2.16 (–1.55; 5.87)	1.60 (1.22; 1.98)^*
ESAS-r nausea	0.31 (–0.09; 0.71)	0.10 (–0.5; 0.71)	0.20 (–0.80; 1.20)	–0.20 (–0.81; 0.40)	–0.11 (–1.11; 0.90)	0.10 (–1.01; 1.20)	–0.26 (–0.59; 0.08)	0.51 (–2.12; 3.15)	0.77 (–1.86; 3.40)	0.11 (–0.16; 0.39)
ESAS-r shortness of breath	0.16 (–0.38; 0.70)	–0.21 (–1.02; 0.60)	–0.40 (–1.74; 0.95)	–0.36 (–1.18; 0.45)	–0.55 (–1.90; 0.79)	–0.19 (–1.67; 1.29)	0.10 (–0.35; 0.55)	0.07 (–3.46; 3.60)	–0.03 (–3.56; 3.49)	0.38 (0.02; 0.75)
ESAS-r lack of appetite	0.28 (–0.22; 0.79)	0.47 (–0.30; 1.24)	–0.41 (–1.69; 0.87)	0.18 (–0.59; 0.96)	–0.69 (–1.98; 0.59)	–0.88 (–2.28; 0.53)	–0.65 (–1.07; –0.22)^*	1.21 (–2.14; 4.57)	1.86 (–1.49; 5.21)	0.16 (–0.18; 0.51)
ESAS-r wellbeing	0.45 (–0.01; 0.91)	–0.17 (–0.87; 0.52)	0.01 (–1.15; 1.16)	–0.62 (–1.32; 0.08)	–0.44 (–1.60; 0.71)	0.18 (–1.09; 1.44)	–0.04 (–0.42; 0.35)	0.4 (–2.62; 3.43)	0.44 (–2.58; 3.46)	0.84 (0.53; 1.16)^*
SF-36 physical HRQoL	–4.77 (–8.09; –1.44)^*	2.90 (–2.13; 7.94)	3.39 (–4.97; 11.74)	7.67 (2.6; 12.74)^*	8.16 (–0.22; 16.53)	0.48 (–8.7; 9.67)	1.53 (–1.25; 4.31)	–3.05 (–24.98; 18.88)	–4.58 (–26.51; 17.35)	–6.75 (–9.02; –4.48)^*
SF-36 mental HRQoL	–3.79 (–7.70; 0.12)	–2.34 (–8.26; 3.57)	1.33 (–8.49; 11.15)	1.45 (–4.51; 7.41)	5.26 (–4.72; 14.97)	3.68 (–7.12; 14.48)	3.08 (–0.18; 6.36)	–19.05 (–44.83; 3.64)	–22.13 (–47.91; 3.64)	–7.92 (–10.59;–5.25)^*

^a A narrow CI indicates a more precise estimate of the mean difference whereas a wider interval points to a less precise estimation. CI that crosses through zero, with a negative lower bound value and a positive upper bound value suggests there is not enough evidence to conclude on a difference between the means; ^b an estimate of the modified population marginal mean for mixed and undefined categories; ^c An estimate of the modified population marginal mean for THC-dominant category; ^* significance set at P < 0.01

Declarations

Acknowledgments

The authors thank the participants in this study and the medical professionals and clinic staff for collection of data. The authors also thank Youri Drozd and Charlotte Bastin for technical support.

Author contributions

LR, MFA, and EP: Conceptualization. LR: Data curation, Formal analysis, Writing—original draft. MFA: Resources. EP: Supervision. MFA, EP, CS, AW, and DD: Writing—review and editing.

Conflicts of interest

All authors have a relationship with Santé Cannabis, a medical cannabis clinic and research centre based in Montreal, Québec, Canada. Santé Cannabis operates within the public healthcare system, patients do not pay fees to receive care at the clinic. Santé Cannabis does not sell, or receive financial benefit from the sale of medical cannabis.

Ethical approval

The registry, from which the submitted data is extracted, was approved by the McGill University Faculty of Medicine and Health Sciences Ethics Committee (ID A07-E47-20B/20-07-004). The study was conducted in accordance with the Declaration of Helsinki.

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The datasets for this manuscript are not publicly available because they are not part of a public repository. Requests for accessing the datasets should be directed to Lucile Rapin, lrapin@santecannabis.ca.

Funding

Not applicable.

Copyright

References

Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011;11:770. [DOI] [PubMed] [PMC]

Kosek E, Cohen M, Baron R, Gebhart GF, Mico JA, Rice ASC, et al. Do we need a third mechanistic descriptor for chronic pain states? Pain. 2016;157:1382–6. [DOI] [PubMed]

MacCallum CA, Eadie L, Barr AM, Boivin M, Lu S. Practical strategies using medical cannabis to reduce harms associated with long term opioid use in chronic pain. Front Pharmacol. 2021;12:633168. [DOI] [PubMed] [PMC]

Marel C, Sunderland M, Mills KL, Slade T, Teesson M, Chapman C. Conditional probabilities of substance use disorders and associated risk factors: progression from first use to use disorder on alcohol, cannabis, stimulants, sedatives and opioids. Drug Alcohol Depend. 2019;194:136–42. [DOI] [PubMed]

Urits I, Gress K, Charipova K, Habib K, Lee D, Lee C, et al. Use of cannabidiol (CBD) for the treatment of chronic pain. Best Pract Res Clin Anaesthesiol. 2020;34:463–77. [DOI] [PubMed]

Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162:276–86. [DOI] [PubMed]

National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington (DC): National Academies Press (US); 2017. [DOI] [PubMed]

Aviram J, Pud D, Gershoni T, Schiff-Keren B, Ogintz M, Vulfsons S, et al. Medical cannabis treatment for chronic pain: outcomes and prediction of response. Eur J Pain. 2021;25:359–74. [DOI] [PubMed]

Urits I, Borchart M, Hasegawa M, Kochanski J, Orhurhu V, Viswanath O. An update of current cannabis-based pharmaceuticals in pain medicine. Pain Ther. 2019;8:41–51. [DOI] [PubMed] [PMC]

10.

Vulfsons S, Minerbi A, Sahar T. Cannabis and pain treatment—a review of the clinical utility and a practical approach in light of uncertainty. Rambam Maimonides Med J. 2020;11:e0002. [DOI] [PubMed] [PMC]

11.

Ueberall MA, Essner U, Vila Silván C, Mueller-Schwefe GHH. Comparison of the effectiveness and tolerability of nabiximols (THC:CBD) oromucosal spray versus oral dronabinol (THC) as add-on treatment for severe neuropathic pain in real-world clinical practice: retrospective analysis of the German Pain e-Registry. J Pain Res. 2022;15:267–86. [DOI] [PubMed] [PMC]

12.

Lötsch J, Weyer-Menkhoff I, Tegeder I. Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings. Eur J Pain. 2018;22:471–84. [DOI] [PubMed]

13.

Vučković S, Srebro D, Vujović KS, Vučetić Č, Prostran M. Cannabinoids and pain: new insights from old molecules. Front Pharmacol. 2018;9:1259. [DOI] [PubMed] [PMC]

14.

Meng H, Page MG, Ajrawat P, Deshpande A, Samman B, Dominicis M, et al. Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in chronic pain patients. Can J Anaesth. 2021;68:633–44. [DOI] [PubMed]

15.

Sexton M, Cuttler C, Finnell JS, Mischley LK. A cross-sectional survey of medical cannabis users: patterns of use and perceived efficacy. Cannabis Cannabinoid Res. 2016;1:131–8. [DOI] [PubMed] [PMC]

16.

Ueberall MA, Essner U, Mueller-Schwefe GH. 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;12:1577–604. [DOI] [PubMed] [PMC]

17.

Lucas P, Baron EP, Jikomes N. Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients. Harm Reduct J. 2019;16:9. [DOI] [PubMed] [PMC]

18.

Campbell G, Hall WD, Peacock A, Lintzeris N, Bruno R, Larance B, et al. Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study. Lancet Public Health. 2018;3:e341–50. [DOI] [PubMed] [PMC]

19.

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. [DOI] [PubMed] [PMC]

20.

Nutt DJ, Phillips LD, Barnes MP, Brander B, Curran HV, Fayaz A, et al. A Multicriteria decision analysis comparing pharmacotherapy for chronic neuropathic pain, including cannabinoids and cannabis-based medical products. Cannabis Cannabinoid Res. 2022;7:482–500. [DOI] [PubMed] [PMC]

21.

Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018;159:1932–54. [DOI] [PubMed]

22.

Wong SSC, Chan WS, Cheung CW. Analgesic effects of cannabinoids for chronic non-cancer pain: a systematic review and meta-analysis with meta-regression. J Neuroimmune Pharmacol. 2020;15:801–29. [DOI] [PubMed]

23.

Meng H, Johnston B, Englesakis M, Moulin DE, Bhatia A. Selective cannabinoids for chronic neuropathic pain: a systematic review and meta-analysis. Anesth Analg. 2017;125:1638–52. [DOI] [PubMed]

24.

Petzke F, Tölle T, Fitzcharles MA, Häuser W. Cannabis-based medicines and medical cannabis for chronic neuropathic pain. CNS Drugs. 2022;36:31–44. [DOI] [PubMed] [PMC]

25.

Campbell G, Stockings E, Nielsen S. Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. Eur Arch Psychiatry Clin Neurosci. 2019;269:135–44. [DOI] [PubMed]

26.

Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010;182:E694–701. [DOI] [PubMed] [PMC]

27.

Crescioli G, Lombardi N, Bettiol A, Menniti-Ippolito F, Da Cas R, Parrilli M, et al. Adverse events following cannabis for medical use in Tuscany: an analysis of the Italian Phytovigilance database. Br J Clin Pharmacol. 2020;86:106–20. [DOI] [PubMed] [PMC]

28.

Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study team. Cannabis for the management of pain: assessment of safety study (COMPASS). J Pain. 2015;16:1233–42. [DOI] [PubMed]

29.

Cannabis for medical purposes under the Cannabis Act: information and improvements [Internet]. Health Canada; [cited 2021 Sep 22]. Available from: https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/medical-use-cannabis.html

30.

Bhaskar A, Bell A, Boivin M, Briques W, Brown M, Clarke H, et al. Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process. J Cannabis Res. 2021;3:22. [DOI] [PubMed] [PMC]

31.

Prosk E, Arboleda MF, Rapin L, El Hage C, Dworkind M. The model of care at a leading medical cannabis clinic in Canada. Complement Ther Med. 2021;60:102740. [DOI] [PubMed]

32.

Hui D, Bruera E. The Edmonton symptom assessment system 25 years later: past, present, and future developments. J Pain Symptom Manage. 2017;53:630–43. [DOI] [PubMed] [PMC]

33.

Cleeland CS. Brief pain inventory short form [Internet]. [cited 2022 Sep 12]. Available from: https://psycnet.apa.org/doiLanding?doi=10.1037%2Ft04175-000

34.

Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 health survey manual and interpretation guide. Boston: Nimrod Press; 1993.

35.

IBM SPSS Statistics 24. Version 24.0 [software]. 2016 [cited 2021 Aug 1]. Available from: https://www.ibm.com/support/pages/downloading-ibm-spss-statistics-24

36.

Hayes C, Martin JH. Lack of efficacy of cannabidiol for relieving back pain: time to re-set expectations? Med J Aust. 2021;214:360–1. [DOI] [PubMed]

37.

Häuser W, Finn DP, Kalso E, Krcevski-Skvarc N, Kress HG, Morlion B, et al. European Pain Federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. Eur J Pain. 2018;22:1547–64. [DOI] [PubMed]

38.

Wolf J, Urits I, Orhurhu V, Peck J, Orhurhu MS, Giacomazzi S, et al. The role of the cannabinoid system in pain control: basic and clinical implications. Curr Pain Headache Rep. 2020;24:35. [DOI] [PubMed]

39.

Kalaba M, MacNair L, Peters EN, Eglit GML, Rapin L, Hage CE, et al. Authorization patterns, safety, and effectiveness of medical cannabis in Quebec. Cannabis Cannabinoid Res. 2021;6:564–72. [DOI] [PubMed] [PMC]

40.

Lintzeris N, Mills L, Suraev A, Bravo M, Arkell T, Arnold JC, et al. Medical cannabis use in the Australian community following introduction of legal access: the 2018–2019 Online Cross-Sectional Cannabis as Medicine Survey (CAMS-18). Harm Reduct J. 2020;17:37. [DOI] [PubMed] [PMC]

41.

Sihota A, Smith BK, Ahmed SA, Bell A, Blain A, Clarke H, et al. Consensus-based recommendations for titrating cannabinoids and tapering opioids for chronic pain control. Int J Clin Pract. 2021;75:e13871. [DOI] [PubMed] [PMC]

42.

MacCallum CA, Lo LA, Boivin M. “Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations. Eur J Intern Med. 2021;89:10–8. [DOI] [PubMed]

43.

Brunetti P, Pichini S, Pacifici R, Busardò FP, Del Rio A. Herbal preparations of medical cannabis: a vademecum for prescribing doctors. Medicina (Kaunas). 2020;56:237. [DOI] [PubMed] [PMC]

44.

Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163:1344–64. [DOI] [PubMed] [PMC]

45.

Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ. 2008;178:1669–78. [DOI] [PubMed] [PMC]

46.

Drug Interactions Flockhart Table ™ [Internet]. Bloomington: The Trustees of Indiana University; c2023 [cited 2022 Aug 30]. Available from: https://drug-interactions.medicine.iu.edu/MainTable.aspx

47.

Alkabbani W, Marrie RA, Bugden S, Alessi-Severini S, Bolton JM, Daeninck P, et al. Persistence of use of prescribed cannabinoid medicines in Manitoba, Canada: a population-based cohort study. Addiction. 2019;114:1791–9. [DOI] [PubMed]

48.

First L, Douglas W, Habibi B, Singh JR, Sein MT. Cannabis use and low-back pain: a systematic review. Cannabis Cannabinoid Res. 2020;5:283–9. [DOI] [PubMed] [PMC]

49.

Brenneisen R. Chemistry and analysis of phytocannabinoids and other cannabis constituents. In: ElSohly MA, editor. Marijuana and the cannabinoids. Totowa: Humana Press; 2007. pp. 17–49. [DOI]