Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Narrative Review

Cannabis and pain: a scoping review

Camila Pantoja-Ruiz; Paula Restrepo Jimenez; Camilo Castañeda-Cardona; Diego Rosselli

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For centuries, cannabis has been used with many different purposes, including medicinal use, usually bypassing any formal approval process. However, during the last decade, interest in cannabis in medicine has been increasing, and several countries, including the United States and Canada, have produced their own legislation about marihuana and cannabis-based medicines. Because of this, interest in research has been increasing and evidence about its medical effects is becoming necessary.

We conducted a review examining the evidence of cannabis in pain. Cannabis had been shown to be useful in acute and chronic pain, however recently these results have been controverted. Within the different types of chronic pain, it has a weak evidence for neuropathic, rheumatic pain, and headache, modest evidence for multiple sclerosis related pain, and as adjuvant therapy in cancer pain. There is no strong evidence to recommend cannabis in order to decrease opioids in patients with chronic use.

Even though cannabis-based medications appear to be mostly safe, mild adverse effects are common; somnolence, sedation, amnesia, euphoric mood, hyperhidrosis, paranoia, and confusion may limit the use of cannabis in clinical practice. Risks have not been systematically analyzed. Special concern arises on how adverse effect might affect vulnerable population such as elderly patients.

More research is needed in order to evaluate benefits and risks, as well as the ideal administration route and dosages. As cannabis use increases in several countries, answers to these questions might be coming soon.


Acute pain;  Cannabis;  Neuralgia;  Review;  Chronic pain;  Cancer pain


1 K.P. Hill, M.D. Palastro, B. Johnson, et al. Cannabis and pain: a clinical review Cannabis Cannabinoid Res., 2 (2017), pp. 96-104

2 M. Touw, A. Arboretum The religious and medicinal uses of Cannabis in China, India and Tibet J Psychoactive Drugs., 13 (1981), pp. 23-34

3 AW Zuardi History of cannabis as a medicine: a review Rev Bras Psiquiatr., 28 (2006), pp. 153-157

4 T. Mikuriya Marijuana in medicine: past, present and future Calif Med., 110 (1969), pp. 34-40

5 LL Bowen, AL McRae-Clark Therapeutic benefit of smoked cannabis in randomized placebo-controlled studies Pharmacotherapy., 38 (2018), pp. 80-85

6 B. Jensen, J. Chen, T. Furnish, et al. Medical marijuana and chronic pain: a review of basic science and clinical evidence Curr Pain Headache Rep., 19 (2015), p. 50

7 F. Grotenhermen, E Russo Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential Psychology Press (2002)

8 M.A. Fitzcharles, E. Eisenberg Medical cannabis: a forward vision for the clinician Eur J Pain., 22 (2018), pp. 485-491

9 National Conference of State Legislatures State medical marijuana laws (2016)

10 ME Lynch Cannabinoids in the management of chronic pain: a front line clinical perspective J Basic Clin Physiol Pharmacol., 27 (2016), pp. 189-191

11 W. Hauser, M.-A. Fitzcharles, L. Radbruch, et al. Cannabinoids in pain management and palliative medicine Dtsch Arztebl Int., 114 (2017), pp. 627-634

12 R. Pertwee Cannabinoid pharmacology: the first 66 years Br J Pharmacol., 147 (2006), pp. S163-71

13 D. Demuth, A. Molleman Cannabinoid signaling Life Sci., 78 (2006), pp. 549-563

14 Y. Gaoni, R. Mechoulam Isolation, structure and partial synthesis of an active constituent of hashish J Am Chem Soc., 86 (1964), pp. 1646-1647

15 G. Ljubiša A comparative study on some chemical and biological characteristics of various samples of cannabis resin Bull Narc., 3 (1962) 37.6

16 MR Amin, DW Ali Pharmacology of medical cannabis Adv Exp Med Biol., 1162 (2019), pp. 151-165

17 D. Pascual, E.M. Sanchez-Robles, M.M. Garcia, et al. Chronic pain and cannabinoids. Great expectations or a christmas carol Biochem Pharmacol., 157 (2018), pp. 33-42

18 EB Russo Cannabinoids in the management of difficult to treat pain Ther Clin Risk Manag., 4 (2008), pp. 245-259

19 M Steiner, CT Wotjak Role of the endocannabinoid system in regulation of the hypothalamic-pituitary-adrenocortical axis Prog Brain Res., 170 (2008), pp. 397-432

20 K. Starowicz, N. Malek, B. Przewlocka Cannabinoid receptors and pain Wiley Interdiscip Rev Membr Transp Signal., 2 (2013), pp. 121-132

21 I. Urits, M. Borchart, M. Hasegawa, et al. An update of current cannabis-based pharmaceuticals in pain medicine Pain Ther., 8 (2019), pp. 41-51

22 AC Howlett A short guide to the nomenclature of seven- transmembrane spanning receptors for lipid mediators Life Sci., 77AD (2005), pp. 1522-1530

23 RG Pertwee Cannabinoid pharmacology: the first 66 years Br J Pharmacol., 147 (2006), pp. S163-S171

24 RG Pertwee The pharmacology of cannabinoid receptors and their ligands: an overview Int J Obes., 30 (2006), pp. S13-8

25 R. Mlezack, P. Wall Pain mechanisms: a new theory Science (80-)., 150 (1965), pp. 971-979

26 J. Koenig, R. Werdehausen, J.E. Linley, et al. Regulation of Nav1.7: a conserved SCN9A natural antisense transcript expressed in dorsal root ganglia PLoS One., 10 (2015), pp. 1-14

27 M. Kremer Antidepressants and gabapentinoids in neuropathic pain: mechanistic insights Neuroscience., 338 (2016), pp. 183-206

28 L.M. Arnold, E. Choy, D.J. Clauw, et al. Fibromyalgia and chronic pain syndromes: A white paper detailing current challenges in the field Clin J Pain., 32 (2016), pp. 737-746

29 K Starowicz, DP Finn Cannabinoids and pain: sites and mechanisms of action Adv Pharmacol., 80 (2017), pp. 437-475

30 Y. Cheng, S. Hitchcock Targeting cannabinoid agonists for inflammatory and neuropathic pain Expert Opin Investig Drugs., 16 (2007), pp. 951-965

31 A.G. Hohmann, E.M. Briley, M. Herkenham Pre- and postsynaptic distribution of cannabinoid and mu opioid receptors in rat spinal cord Brain Res., 822 (1999), pp. 17-25

32 W.P. Farquhar-Smith, M. Egertova, E.J. Bradbury, et al. Cannabinoid CB(1) receptor expression in rat spinal cord Mol Cell Neurosci., 15 (2000), pp. 510-521

33 J. De Vry, K.R. Jentzsch, E. Kuhl, et al. Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance develop- ment Behav Pharmacol., 15 (2004), pp. 1-12

34 A.V. Derbenev, T.C. Stuart, B.N. Smith Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve J Physiol., 559 (2004), pp. 923-938

35 J.C. Ashton, D. Friberg, C.L. Darlington, et al. Expression of the cannabinoid CB2 receptor in the rat cerebellum: an immunohistochemical study Neurosci Lett., 396 (2006), pp. 113-116

36 A. Malfait, R. Gallily, P. Sumariwalla, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis Proc Natl Acad Sci U S A., 97 (2000), pp. 9561-9566

37 C. Njoo, N. Agarwal, B. Lutz, et al. The cannabinoid receptor CB1 Interacts with the WAVE1 complex and plays a role in actin dynamics and structural plasticity in neurons PLoS Biol., 13 (2015), pp. 1-36

38 W.J. Martin, S.L. Patrick, P.O. Coffin, et al. An examination of the central sites of action of cannabinoid-induced antinociception in the rat Life Sci., 56 (1995), pp. 2103-2109

39 G.C. Hsieh, M. Pai, P. Chandran, et al. Central and peripheral sites of action for CB 2 receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats Br J Pharmacol., 162 (2011), pp. 428-440

40 R. Monhemius, J. Azami, D.L. Green, et al. CB1 receptor mediated analgesia from the nucleus reticularis gigantocellularis pars alpha is activated in an animal model of neuropathic pain Brain Res., 908 (2001), pp. 67-74

41 W. Escobar, K. Ramirez, C. Avila, et al. Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats Eur J Pain., 16 (2012), pp. 676-689

42 G. Ji, V. Neugebauer CB1 augments mGluR5 function in medial prefrontal cortical neurons to inhibit amygdala hyperactivity in an arthritis pain model Eur J Neurosci., 1 (2012), pp. 233-245

43 S.J.R. Elmes, M.D. Jhaveri, D. Smart, et al. Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naive rats and in rat models of inflammatory and neuropathic pain Eur J Neurosci., 20 (2004), pp. 2311-2320

44 NM Strangman, JM Walker Cannabinoid WIN 55,212-2 inhibits the activity-dependent facilitation of spinal nociceptive responses J Neurophysiol., 82 (1999), pp. 472-477

45 S. Petrosino, E. Palazzo, V. de Novellis, et al. Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats Neuropharmacology., 52 (2007), pp. 415-422

46 G. Lim, B. Sung, R.R. Ji, et al. Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats Pain., 105 (2003), pp. 275-283

47 P. Beaulieu Cannabinoids for postoperative pain Anesthesiology., 106 (2007), p. 397

48 A. Holdcroft, M. Maze, C. Doré, et al. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management Anesthesiology., 104 (2006), pp. 1040-1046

49 D.J. Buggy, L. Toogood, S. Maric, et al. Lack of analgesic efficacy of oral δ-9-tetrahydrocannabinol in postoperative pain Pain., 106 (2003), pp. 169-172

50 P. Beauliu Effects of nabilone, a synthetic cannabinoid, on postoperative pain Can J Anesth., 53 (2006), pp. 769-775

51 D. Raft, J. Gregg, J. Ghia, et al. Effects of intravenous tetrahydrocannabinol on experimental and surgical pain: psychological correlates of the analgesic response Clin Pharmacol Ther., 21 (1977), pp. 26-33

[52] A. Jain, J. Ryan, G. McMahon, et al. Evaluation of intramuscular levonantradol and placebo in acute postoperative pain J Clin Pharmacol., 21 (1981) 320S-6

53 Q. Aziz, A. Barke, M.I. Bennett, et al. A classification of chronic pain for ICD-11 Pain., 156 (2015), pp. 1003-1007

54 H. Johal, T. Devji, Y. Chang, et al. Cannabinoids in chronic non-cancer pain: a systematic review and meta-analysis Clin Med Insights Arthritis Musculoskelet Disord., 13 (2020) 1179544120906461

55 T. Jensen, R. Baron, M. Haanpää, et al. A new definition of neuropathic pain Pain., 152 (2011), pp. 2205-2206

56 M. Mucke, T. Phillips, L. Radbruch, et al. Cannabis-based medicines for chronic neuropathic pain in adults Cochrane database Syst Rev., 3 (2018), pp. 1-102

57 M. Lunn, R. Hughes, P. Wiffen Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia Cochrane Database Syst Rev. (2014) CD007115

58 R. Moore, S. Straube, P. Wiffen, et al. Pregabalin for acute and chronic pain in adults Cochrane Database Syst Rev. (2009) CD007076

59 D.I. Abrams, C.A. Jay, S.B. Shade, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial Neurology., 68 (2007), pp. 515-521

60 R.J. Ellis, W. Toperoff, F. Vaida, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial Neuropharmacology., 34 (2011), pp. 672-680

61 M.A. Ware, T. Wang, S. Shapiro, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial CMAJ., 182 (2010), pp. E694-701

62 B. Wilsey, T. Marcotte, A. Tsodikov, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain J Pain., 15 (2016), pp. 477-491

63 B. Wilsey, T. Marcotte, A. Tsodikov, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain J Pain., 9 (2008), pp. 506-521

64 N.B. Finnerup, S.H. Sindrup, T.S. Jensen The evidence for pharmacological treatment of neuropathic pain Pain., 150 (2010), pp. 573-581

65 N.B. Finnerup, N. Attal, S. Haroutounian, et al. Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations Lancet Neurol., 14 (2016), pp. 162-173

66 J. Rice, M. Cameron Cannabinoids for treatment of MS symptoms: state of the evidence Curr Neurol Neurosci Rep., 18 (2018), p. 50

67 K. Akgün, U. Essner, C. Seydel, et al. Daily practice managing resistant multiple sclerosis spasticity with delta-9-tetrahydrocannabinol: Cannabidiol oromucosal spray: a systematic review of observational studies J Cent Nerv Syst Dis., 11 (2019) 1179573519831997

68 S. Colfield, A. Salter, T. Tyry, et al. Perspectives on marijuana use and effectiveness Neurol Clin Pract., 7 (2017), pp. 333-343

69 P.L. Foley, H.M. Vesterinen, B.J. Laird, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis Pain., 154 (2013), pp. 632-642

70 J.P. Zajicek, H.P. Sanders, D.E. Wright, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up J Neurol Neurosurg Psychiatry., 76 (2005), pp. 1664-1669

71 J.P. Zajicek, J.C. Hobart, A. Slade, et al. Multiple sclerosis and extract of cannabis: results of the MUSEC trial J Neurol Neurosurg Psychiatry., 83 (2012), pp. 1125-1132

72 D. Turcotte, M. Doupe, M. Torabi, et al. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial Pain Med (United States)., 16 (2015), pp. 149-159

73 ME Lynch, MA Ware Cannabinoids for the Treatment of chronic non-cancer pain: an updated systematic review of randomized controlled trials J Neuroimmune Pharmacol., 10 (2015), pp. 293-301

74 M. Iskedjian, B. Bereza, A. Gordon, et al. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain Curr Med Res Opin., 23 (2007), pp. 17-24

75 M.-A. Fitzcharles, C. Baerwald, J. Ablin, et al. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): a systematic review of randomized controlled trials Schmerz., 30 (2016), pp. 47-61

76 M.-A. Fitzcharles, W. Hauser Cannabinoids in the management of musculoskeletal or rheumatic diseases Curr Rheumatol Rep., 18 (2016), p. 76

77 T. Gonen, H. Amital Cannabis and cannabinoids in the treatment of rheumatic diseases Rambam Maimonides Med J., 11 (2020), p. e0007

78 D. Richardson, R.G. Pearson, N. Kurian, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis Arthritis Res Ther., 10 (2008), pp. 1-14

79 D.R. Blake, P. Robson, M. Ho, et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis Rheumatology., 45 (2006), pp. 50-52

80 R.Q. Skrabek, L. Galimova, K. Ethans, et al. Nabilone for the treatment of pain in fibromyalgia J Pain., 9 (2008), pp. 164-173

81 M. Pinsger, W. Schimetta, D. Volc, et al. Nutzen einer Add-On-Therapie mit dem synthetischen Cannabinomimetikum Nabilone bei Patienten mit chronischen Schmerzzuständen - Eine randomisierte kontrollierte Studie Wien Klin Wochenschr., 118 (2006), pp. 327-335

82 M.-A. Fitzcharles, P.A. Ste-Marie, W. Hauser, et al. Efficacy, Tolerability, and safety of cannabinoid treatments in the rheumatic diseases: a systematic review of randomized controlled trials Arthritis Care Res (Hoboken)., 68 (2016), pp. 681-688

83 B. Walitt, P. Klose, M.-A. Fitzcharles, et al. Cannabinoids for fibromyalgia Cochrane database Syst Rev., 7 (2016) CD011694

84 MHJ Van Den Beuken-Van Everdingen, LMJ Hochstenbach, EAJ Joosten, et al. Update on prevalence of pain in patients with cancer: systematic review and meta-analysis J Pain Symptom Manage., 51 (2016) 1070-1090.e9.

85 T. Meuser, C. Pietruck, L. Radbruch, et al. Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology Pain., 93 (2001), pp. 247-257

86 S. Tateo State of the evidence: cannabinoids and cancer pain-A systematic review J Am Assoc Nurse Pract., 29 (2017), pp. 94-103

87 S.Y. Liang, S.F. Wu, T.C. Chao, et al. The impact of pain on the quality of life of Taiwanese oncology patients Pain Manag Nurs., 16 (2015), pp. 128-136

88 S.S.C. Wong, W.S. Chan, C.W. Cheung Analgesic effects of cannabinoids for chronic non-cancer pain: a systematic review and meta-analysis with meta-regression J Neuroimmune Pharmacol., 15 (2020), pp. 801-829

89 J.R. Johnson, M. Burnell-Nugent, D. 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., 39 (2010), pp. 167-179

90 J.R. Johnson, D. Lossignol, M. Burnell-Nugent, et al. 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., 46 (2013), pp. 207-218

91 R.K. Portenoy, E.D. Ganae-Motan, S. Allende, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial J Pain., 13 (2012), pp. 438-449

92 A.H. Lichtman, E.A. Lux, R. McQuade, 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., 55 (2018) 179-188.e1

93 T.D. Brisbois, I.H. de Kock, S.M. Watanabe, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial Ann Oncol., 22 (2011), pp. 2086-2093

94 C. Levy, E. Galenbeck, K. Magid Cannabis for symptom management in older adults Med Clin North Am., 104 (2020), pp. 471-489

95 XH Hu Burden of migraine in the United States Arch Intern Med [Internet]., 159 (1999), p. 813

96 B.C. Lochte, A. Beletsky, N.K. Samuel, et al. The Use of cannabis for headache disorders Cannabis Cannabinoid Res., 2 (2017), pp. 61-71

97 D.N. Rhyne, S.L. Anderson, M. Gedde, et al. Effects of medical marijuana on migraine headache frequency in an adult population Pharmacotherapy., 36 (2016), pp. 505-510

98 M.S. Robbins, S. Tarshish, S. Solomon, et al. Cluster attacks responsive to recreational cannabis and dronabinol Headache., 49 (2009), pp. 914-916

99 E. Leroux, I. Taifas, D. Valade, et al. Use of cannabis among 139 cluster headache sufferers Cephalalgia., 33 (2013), pp. 208-213

100 L.A. Pini, S. Guerzoni, M.M. Cainazzo, et al. Nabilone for the treatment of medication overuse headache: Results of a preliminary double-blind, active-controlled, randomized trial J Headache Pain., 13 (2012), pp. 677-684

101 S. Calcaterra, J. Glanz, I.A. Binswanger National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009 Drug Alcohol Depend., 131 (2013), pp. 263-270

102 D.I. Abrams, M. Guzman Cannabis in cancer care Clin Pharmacol Ther., 97 (2015), pp. 575-586

103 S.P. Khan, T.A. Pickens, D.J. Berlau Perspectives on cannabis as a substitute for opioid analgesics Pain Manag., 9 (2019), pp. 191-203

104 D.I. Abrams, P. Couey, S.B. Shade, et al. Cannabinoid-opioid interaction in chronic pain Clin Pharmacol Ther., 90 (2011), pp. 844-851

105 M.A. Bachhuber, B. Saloner, C.O. Cunningham, et al. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010 JAMA Intern Med., 174 (2014), pp. 1668-1673

106 M.A. Ware, T. Wang, S. Shapiro, et al. Cannabis for the management of pain: Assessment of Safety Study (COMPASS) J Pain., 16 (2015), pp. 1233-1242

107 S.M. Nugent, B.J. Morasco, M.E. O’Neil, et al. The effects of cannabis among adults with chronic pain and an overview of general harms: a systematic review Ann Intern Med., 167 (2017), pp. 319-331

108 A. Minerbi, W. Hauser, M.-A. Fitzcharles Medical cannabis for older patients Drugs Aging., 36 (2019), pp. 39-51

109 N.G. Choi, C.N. Marti, D.M. DiNitto, et al. Older adults’ marijuana use, injuries, and emergency department visits Am J Drug Alcohol Abuse., 44 (2018), pp. 215-223

110 M.K. Maharajan, Y.J. Yong, H.Y. Yip, et al. Medical cannabis for chronic pain: can it make a difference in pain management? J Anesth., 34 (2020), pp. 95-103

111 A. Zalesky, N. Solowij, M. Yücel, et al. Effect of long-term cannabis use on axonal fibre connectivity Brain., 135 (2012), pp. 2245-2255

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