Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.5935/2595-0118.20230089-en
Brazilian Journal of Pain
Review Article

Use of cannabis and its derivates in chronic pain management: systematic review

Uso de cannabis e seus derivados no manejo da dor crônica: revisão sistemática

Dorgival Nafs Pinto da Silva Lopes Júnior; Breno de Medeiros Bonfim; Ricardo Wagner Gomes da Silva Neto; Alexandre Magno da Nóbrega Marinho

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Abstract

BACKGROUND AND OBJECTIVES: Chronic pain is a clinical condition that affects an important part of the Brazilian and world population, significantly affecting their lives. The medicinal properties of Cannabis have been explored for millennia, but recently its use for the relief of chronic pain symptoms has increased.
CONTENTS: A systematic review was carried out with the objective of evaluating the use of cannabis and its derivatives in the management of chronic pain, analyzing its potential side effects and safety. For this, the following databases were used: Pubmed, Embase, Cochrane Library and BVS, searching for studies published in the last 5 years, in Portuguese, Spanish or English, using MeSH descriptors and relevant free terms. Randomized, double-blind clinical trials with at least 10 participants in each comparison arm and with at least 2 weeks of intervention were included. After screening the authors, a quantitative analysis of 4 clinical trials (586 patients) was performed, which were analyzed for the outcomes of: patients with 50% or 30% reduction in pain intensity compared to baseline, improvement in pain intensity average pain, discontinuation due to adverse effects, serious adverse effects, and any adverse effects.
CONCLUSION: The analysis did not yield high-quality evidence pertaining to the evaluation of efficacy, safety, or adverse effects associated with the use of cannabis-derived treatments in the management of chronic pain. Consequently, the formulation of recommendations or restrictions in these regards is not feasible, leaving the utilization of these therapeutic modalities subject to individual assessment.

Keywords

Cannabidiol, Cannabis, Chronic pain, Dronabinol, Systematic review

Resumo

JUSTIFICATIVA E OBJETIVOS: A dor crônica é uma condição clínica que atinge parte importante da população brasileira e mundial, afetando significativamente a vida dessas pessoas. As propriedades medicinais da Cannabis vêm sendo exploradas por milênios, mas recentemente seu uso para alívio dos sintomas da dor crônica tem aumentado. 
CONTEÚDO: Foi conduzida uma revisão sistemática com o objetivo de avaliar o uso de cannabis e seus derivados no manejo da dor crônica, analisando seus potenciais efeitos adversos e sua segurança. Para isso, foram utilizadas as seguintes bases de dados: PubMed, Embase, Cochrane Library e BVS, buscando estudos publicados nos últimos 5 anos, nos idiomas português, espanhol ou inglês, utilizando os descritores MeSH e termos livres relevantes. Foram incluídos ensaios clínicos randomizados, duplos-cegos, com pelo menos 10 participantes em cada braço de comparação e com no mínimo 2 semanas de intervenção. Após a triagem dos autores, foi procedida a análise quantitativa de 4 ensaios clínicos (586 pacientes), que foram analisados para os desfechos de: pacientes com redução da intensidade da dor 50% ou 30% em relação à linha de base, melhora na intensidade média da dor, descontinuidade devido a efeitos adversos, efeitos adversos graves e qualquer efeito adverso. 
CONCLUSÃO: Não foram encontradas evidências de alta qualidade quanto à avaliação dos desfechos de eficácia, segurança ou de efeitos adversos relacionados ao uso de tratamentos derivados da cannabis no manejo de dor crônica, não podendo ser produzidas recomendações ou restrições nesses aspectos, ficando o uso dessas modalidades terapêuticas sujeito a análise individual.

Palavras-chave

Canabidiol, Cannabis, Dor crônica, Dronabinol, Revisão sistemática

References

1 Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, Keefe FJ, Mogil JS, Ringkamp M, Sluka KA, Song XJ, Stevens B, Sullivan MD, Tutelman PR, Ushida T, Vader K. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976-82.

2 Rahn EJ, Hohmann AG. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 2009;6(4):713-37.

3 GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211-59.

4 de Souza JB, Grossmann E, Perissinotti DMN, de Oliveira Junior JO, da Fonseca PRB, Posso IP. Prevalence of Chronic Pain, Treatments, Perception, and Interference on Life Activities: Brazilian Population-Based Survey. Pain Res Manag. 2017;2017:4643830.

5 Chou R, Huffman LH; American Pain Society; American College of Physicians. Nonpharmacologic therapies for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147(7):492-504.

6 Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. 2007;133(4):581-624.

7 Kamper SJ, Apeldoorn AT, Chiarotto A, Smeets RJ, Ostelo RW, Guzman J, van Tulder MW. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain. Cochrane Database Syst Rev. 2014;(9):CD000963.

8 Tsang A, Von Korff M, Lee S, Alonso J, Karam E, Angermeyer MC, Borges GL, Bromet EJ, Demytteneare K, de Girolamo G, de Graaf R, Gureje O, Lepine JP, Haro JM, Levinson D, Oakley Browne MA, Posada-Villa J, Seedat S, Watanabe M. Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders. J Pain. 2008;9(10):883-91.

9 Smith MT, Haythornthwaite JA. How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature. Sleep Med Rev. 2004;8(2):119-32.

10 Dahlhamer J, Lucas J, Zelaya C, Nahin R, Mackey S, DeBar L, Kerns R, Von Korff M, Porter L, Helmick C. Prevalence of chronic pain and high-impact chronic pain among adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):1001-6.

11 Blyth FM, March LM, Brnabic AJ, Cousins MJ. Chronic pain and frequent use of health care. Pain. 2004;111(1-2):51-8.

12 Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization Study in Primary Care. JAMA. 1998;8;280(2):147-51.

13 Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet. 2011;377(9784):2226-35.

14 Volkow ND, McLellan AT. Opioid abuse in chronic pain-misconceptions and mitigation strategies. N Engl J Med. 2016;374(13):1253-63.

15 Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016. JAMA. 2016;315(15):1624-45.

16 Smith SM, Dworkin RH, Turk DC, McDermott MP, Eccleston C, Farrar JT, Rowbotham MC, Bhagwagar Z, Burke LB, Cowan P, Ellenberg SS, Evans SR, Freeman RL, Garrison LP, Iyengar S, Jadad A, Jensen MP, Junor R, Kamp C, Katz NP, Kesslak JP, Kopecky EA, Lissin D, Markman JD, Mease PJ, O’Connor AB, Patel KV, Raja SN, Sampaio C, Schoenfeld D, Singh J, Steigerwald I, Strand V, Tive LA, Tobias J, Wasan AD, Wilson HD. Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations. Pain. 2020;161(11):2446-61.

17 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):735-44.

18 Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-73.

19 Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215.

20 FDA. FDA-Approved Drugs. 2023. Disponível em: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=018651. Acesso em: 14 mar. 2023.

21 Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011;6(4):237-49.

22 Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009;30(10):515-27.

23 Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 2010;70(18):2409-38.

24 Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016;7(7):CD011694.

25 Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

26 Sommer C, Welsch P, Klose P, Schaefert R, Petzke F, Häuser W. Opioids in chronic neuropathic pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration. Schmerz. 2015;29(1):35-46.

27 Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Kornyeyeva E, Fallon MT. 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):179-88.e1.

28 van Amerongen G, Kanhai K, Baakman AC, Heuberger J, Klaassen E, Beumer TL, Strijers RLM, Killestein J, van Gerven J, Cohen A, Groeneveld GJ. Effects on spasticity and neuropathic pain of an oral formulation of δ9-tetrahydrocannabinol in patients with progressive multiple sclerosis. Clin Ther. 2018;40(9):1467-82.

29 Vela J, Dreyer L, Petersen KK, Arendt-Nielsen L, Duch KS, Kristensen S. Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. Pain. 2022;163(6):1206-14.

30 Xu DH, Cullen BD, Tang M, Fang Y. The effectiveness of topical cannabidiol oil in symptomatic relief of peripheral neuropathy of the lower extremities. Curr Pharm Biotechnol. 2020;21(5):390-402.

31 Moore RA, Straube S, Aldington D. Pain measures and cut-offs - ‘no worse than mild pain’ as a simple, universal outcome. Anaesthesia. 2013;68(4):400-12.

32 Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105-21.

33 Moore AR, Eccleston C, Derry S, Wiffen P, Bell RF, Straube S, McQuay H; ACTINPAIN writing group of the IASP Special Interest Group (SIG) on Systematic Reviews in Pain Relief and the Cochrane Pain, Palliative and Supportive Care Systematic Review Group editors. “Evidence” in chronic pain-establishing best practice in the reporting of systematic reviews. Pain. 2010;150(3):386-9.

34 Alessandria G, Meli R, Infante MT, Vestito L, Capello E, Bandini F. Long-term assessment of the cognitive effects of nabiximols in patients with multiple sclerosis: A pilot study. Clin Neurol Neurosurg. 2020;196:105990.

35 Almog S. Metered-Dose Cannabis Inhaler Provides Consistent, Dose-Related THC Blood Concentration and Analgesic Effects, in Patients with Chronic Neuropathic Pain. The 2nd International Annual Congress on Controversies on Cannabis-Based Medicines, Barcelona, Spain, May 23-24, 2019. Med Cannabis Cannabinoids 19 December 2019;2(2):69–83.

36 Sharon H. Cannabis induces changes in functional brain connectivity that correlate with increased vagal tone and clinical analgesia in chronic neuropathic pain. 30th International Symposium on the Autonomic Nervous System. Clin Auton Res. 2019;29:479-546.

37 Weizman L, Dayan L, Brill S, Nahman-Averbuch H, Hendler T, Jacob G, Sharon H. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018;91(14):e1285-e1294.

38 Almog S, Aharon-Peretz J, Vulfsons S, Ogintz M, Abalia H, Lupo T, Hayon Y, Eisenberg E. The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial. Eur J Pain. 2020;24(8):1505-16.

39 van de Donk T, Niesters M, Kowal MA, Olofsen E, Dahan A, van Velzen M. An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain. 2019;160(4):860-9.

40 NCT03984565. Sublingual Cannabidiol for Chronic Pain. In: ClinicalTrials.gov. 2019. Disponível em: https://clinicaltrials.gov/show/NCT03984565. Acesso em: 19 mar. 2023.

41 van Dam CJ, van Velzen M, Kramers C, Schellekens A, Olofsen E, Niesters M, Dahan A. Cannabis-opioid interaction in the treatment of fibromyalgia pain: an open-label, proof of concept study with randomization between treatment groups: cannabis, oxycodone or cannabis/oxycodone combination-the SPIRAL study. Trials. 2023;24(1):64.

42 Poli P, Crestani F, Salvadori C, Valenti I, Sannino C. Medical cannabis in patients with chronic pain: effect on pain relief, pain disability, and psychological aspects. a prospective non randomized single arm clinical trial. Clin Ter. 2018;169(3):e102-e107.

43 Chaves C, Bittencourt PCT, Pelegrini A. Ingestion of a THC-rich cannabis oil in people with fibromyalgia: a randomized, double-blind, placebo-controlled clinical trial. Pain Med. 2020;21(10):2212-8.

44 Gao Y, Li Y, Tan Y, Liu W, Ouaddi S, McCoy J, Kovacevic M, Situm M, Stanimirovic A, Li M, Wambier C, Goren A, Zou Y. Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: results from a randomized double-blinded placebo-controlled interventional study. J Cosmet Dermatol. 2022;21(4):1647-50.

45 Abrams DI, Couey P, Dixit N, Sagi V, Hagar W, Vichinsky E, Kelly ME, Connett JE, Gupta K. Effect of inhaled cannabis for pain in adults with sickle cell disease: a randomized clinical trial. JAMA Netw Open. 2020;3(7):e2010874.

46 Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta- analyses involving cross-over trials: methodological issues. Int J Epidemiol. 2002;31(1):140-9.

47 Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015;29(1):7-14.

48 Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-73.
 


Submitted date:
07/06/2023

Accepted date:
10/11/2023

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