Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.5935/2595-0118.20230012-en
Brazilian Journal of Pain
Artigo de Revisão

Neuropathies and the use of cannabinoids as a therapeutic strategy

Neuropatias e o uso de canabinoides como estratégia terapêutica

Helena Wohlers Sabo; Ana Gabriela Baptista

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Abstract

BACKGROUND AND OBJECTIVES: Prevalence of painful neuropathy is around 7%-10% in the entire population, also, it may have different histories and require integrated care. Challenges for patient care are concerning, most of them have not achieved satisfactory results with drugs for pain management, which are often disabling, in addition to associated comorbidities such as sleep disorders and mood swings. Most of the drugs currently being used for neuropathic pain (NP) have several adverse effects, which hinders adherence to treatment and makes it impossible to reach the doses that would be indicated for proper management. Given this scenario, studies are being done aiming at the endocannabinoid system present in the human body with the ability to modulate pain, sleep, and mood disorders, among other benefits. Drugs such as phytocannabinoids, mainly the molecules cannabidiol (CBD) and tetrahydrocannabidiol (THC), have been studied with significant potential for the treatment of painful neuropathy. This review aimed to describe the probable mechanisms of action of cannabinoids in NP and the results obtained so far with the use of these molecules. 
CONTENTS: This study is a narrative review of the literature. Data were analyzed using the databases National Library of Medicine (NCBI), Academic Google, Medline and scientific database configurations by LILACS and Web of Science in a temporal search between 2004 and 2022. A total of 45 articles were counted. 
CONCLUSION: THC modulates opioid effects in neuropathic pain. This is associated with a pharmacokinetic effect and has also been demonstrated by brain imaging. This significant performance can be associated with specific target sites and primary actors regarding Δ-9-THC and its binding to receptors associated with analgesia. Also, further studies with this component or associated with small cannabinoid variations are necessary to certify its role in neuropathic pain.

Keywords

Cannabidiol, Cannabinoids, Cannabis, Pain

Resumo

JUSTIFICATIVA E OBJETIVOS: A neuropatia dolorosa tem prevalência estimada em toda a população em torno de 7% a 10%, pode ter diversas etiologias e requer cuidado integrado. O cuidado desses pacientes costuma ser desafiador, pois a maioria deles não obtém resultados satisfatórios com os fármacos disponíveis para manejo da dor que, muitas vezes, são incapacitantes, além das comorbidades associadas, como distúrbios do sono e alterações de humor. A maioria dos fármacos utilizados atualmente para o tratamento da dor neuropática (DN) apresenta diversos efeitos adversos, o que dificulta a adesão ao tratamento e impossibilita atingir as doses que seriam indicadas para o manejo adequado. Diante desse cenário, estudos estão sendo feitos visando o sistema endocanabinoide presente no corpo humano, que tem capacidade de modular a dor, sono e distúrbios do humor, entre outros benefícios. Fármacos como os fitocanabinoides, principalmente com as moléculas canabidiol (CBD) e tetrahidrocanabidiol (THC), têm sido estudados com potencial significativo para o tratamento da neuropatia dolorosa. Esta revisão teve o objetivo de descrever os mecanismos prováveis de ação dos canabinoides na DN e os resultados obtidos até o momento com a utilização dessas moléculas. 
CONTEÚDO: Este estudo é uma revisão narrativa da literatura. Os dados foram analisados utilizando as bases de dados National Library of Medicine (NCBI), Google acadêmico, Medline e configurações de bases científicas pela LILACS e Web of Science em uma busca temporal entre 2004 e 2022. Foram contabilizados 45 artigos. 
CONCLUSÃO: O THC modula os efeitos opioides na dor neuropática. Esta atuação é associada com efeito farmacocinético e foi demonstrada por imagens cerebrais. Esta atuação significativa pode ser associada com sítios alvo específicos e atuantes primários com relação ao Δ-9-THC e sua ligação a receptores associados à analgesia. Entretanto, mais estudos com este componente ou associado a pequenas variações canabinoides são necessários para afirmar a sua atuação na dor neuropática.

Palavras-chave

Canabidiol, Canabinoides, Cannabis, Dor.

Referências

1 Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L. Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neurosci Ther. 2009;15(1):65-75.

2 Cao C, Li Y, Liu H, Bai G, Mayl J, Lin X, Sutherland K, Nabar N, Cai J. The potential therapeutic effects of THC on Alzheimer’s disease. J Alzheimers Dis. 2014;42(3):973-84.

3 Rajesh M, Mukhopadhyay P, Bátkai S, Haskó G, Liaudet L, Drel VR, Obrosova IG, Pacher P. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Am J Physiol Heart Circ Physiol. 2007;293(1):H610-9.

4 Ramer R, Bublitz K, Freimuth N, Merkord J, Rohde H, Haustein M, Borchert P, Schmuhl E, Linnebacher M, Hinz B. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. FASEB J. 2012;26(4):1535-48.

5 Yao I, Stein ES, Maggio N. Cannabinoids, hippocampal excitability and efficacy for the treatment of epilepsy. Pharmacol Ther. 2019;202(1):32-9.

6 Calcutt NA. Diabetic neuropathy and neuropathic pain: a (con)fusion of pathogenic mechanisms. Pain. 2020;161(Suppl 1):S65-S86.

7 Zhornitsky S, Potvin S. Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals (Basel). 2012;5(5):529-52.

8 Serpell M, Ratcliffe S, Hovorka J, Schofield M, Taylor L, Lauder H, Ehler E. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014;18(7):999-1012.

9 Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9(2):164-73.

10 Berman JS, Symonds C, Birch R. 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(3):299-306.

11 Baethge C, Goldbeck-Wood S, Mertens S. SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4(1):2-8.

12 Klein TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol. 2005;5(5):400-11.

13 Gross F, Üçeyler N. Mechanisms of small nerve fiber pathology. Neurosci Lett. 2020;15;737:135316.

14 Hansson GK. Neuropathic pain: definition, diagnostic criteria, clinical phenomenology, and differential diagnostic issues. Pain. 2008;2008.

15 Pedowitz EJ, Abrams RMC, Simpson DM. Management of neuropathic pain in the geriatric population. Clin Geriatr Med. 2021;37(2):361-76.

16 Blanton HL, Brelsfoard J, DeTurk N, Pruitt K, Narasimhan M, Morgan DJ, Guindon J. Cannabinoids: current and future options to treat chronic and chemotherapy-induced neuropathic pain. Drugs. 2019;79(9):969-95.

17 Knezevic NN, Jovanovic F, Candido KD, Knezevic I. Oral pharmacotherapeutics for the management of peripheral neuropathic pain conditions – a review of clinical trials. Expert Opin Pharmacother. 2020;21(18):2231-48.

18 Lee G, Grovey B, Furnish T, Wallace M. Medical cannabis for neuropathic pain. Curr Pain Headache Rep. 2018;22(1):8.

19 Kogan NM, Lavi Y, Topping LM, Williams RO, McCann FE, Yekhtin Z, Feldmann M, Gallily R MRN. Novel CBG derivatives can reduce inflammation, pain, and obesity. Molecules. 2021;26:5601.

20 Sopacua M, Hoejimakers JGJ, Merkies ISJ, Lauria G, Waxman SG FC. Small fibre neuropathy: expanding the clinical pain universe. J Peripher Nerv Syst. 2019;24(1):19-23.

21 Alles SRA, Cain SM, Snutch T P. Pregabalin as a pain therapeutic: beyond calcium channels. Front Cell Neurosci. 2020;14:83.

22 Cipriani A. Review: selective serotonin reuptake inhibitors as effective as tricyclic anti-depressants for major depression, and may have fewer adverse effects. Evid Based Ment Health. 2003;6(4):117.

23 Yeh CM, Ruan T, Lin YJ, Hsu TH. Activation of cannabinoid CB1 receptors suppresses the ROS-induced hypersensitivity of rat vagal lung C-fiber afferents. Pulm Pharmacol Ther. 2016 Oct;40:22-9.

24 O’Hearn S, Diaz P, Wan BA, DeAngelis C, Lao N, Malek L, Chow E, Blake A. Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies. Ann Palliat Med. 2017;6(Suppl 2):S209-S214.

25 Maldonado R, Baños JE, Cabañero D. The endocannabinoid system and neuropathic pain. Pain. 2016;157(Suppl 1):S23-S32.

26 Fillingim RB. Individual differences in pain: understanding the mosaic that makes pain personal. Pain. 2017;158(Suppl 1):S11-8.

27 Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, Benoliel R, Cohen M, Cruccu G, Davis KD, Evers S, First M, Giamberardino MA, Hansson P, Kaasa S, Korwisi B, Kosek E, Lavand’homme P, Nicholas M, Nurmikko T, Perrot S, Raja SN, Rice ASC, Rowbotham MC, Schug S, Simpson DM, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ, Barke A, Rief W, Treede RD; Classification Committee of the Neuropathic Pain Special Interest Group (NeuPSIG). The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2019;160(1):53-9.

28 Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther. 2012;133(1):79-97.

29 Klein T W. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol. 2005;5(5):400-11.

30 Morera-Herreras T, Miguelez C, Aristieta A, Ruiz-Ortega JA, Ugedo L. Endocannabi-noid modulation of dopaminergic motor circuits. Front Pharmacol. 2012;3:110.

31 Syed YY, McKeage K, Scott LJ. Delta-9-Tetrahydrocannabinol/cannabidiol (Sativex®): A review of its Use in patients with moderate to severe spasticity due to multiple sclerosis. Drugs. 2014;74(5):563-78.

32 Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013;260(4):984-97

33 Rintala DH, Fiess RN, Tan G, Holmes SA, Bruel BM. Effect of dronabinol on central neuropathic pain after spinal cord injury: A pilot study. Am J Phys Med Rehabil. 2010;89(10):840-8.

34 Schimrigk S, Marziniak M, Neubauer C, Kugler EM, Werner G, Abramov-Sommariva D. Dronabinol is a safe long-term treatment option for neuropathic pain patients. Eur Neurol. 2017;78(5-6):320-9.

35 Wallace MS, Marcotte TD, Atkinson JH, Padovano HT, Bonn-Miller M. A secondary analysis from a randomized trial on the effect of plasma tetrahydrocannabinol levels on pain reduction in painful diabetic peripheral neuropathy. J Pain. 2020;21(11-12):1175-86.

36 Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14(2):136-48.

37 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.

38 Murnion B P. Neuropathic pain: current definition and review of drug treatment. Aust Prescr. 2018;41(3):60-3.

39 Sadler A, Wilson J, Colvin L. Acute and chronic neuropathic pain in the hospital setting: use of screening tools. Clin J Pain. 2013;29(6):507-11.

40 Alshelh Z, Di Pietro F, Youssef AM, Reeves JM, Macey PM, Vickers ER, Peck CC, Murray GM, Henderson LA. Chronic neuropathic pain: it’s about the rhythm. J Neurosci. 2016;36(3):1008-18.

41 Russo M, Naro A, Leo A, Sessa E, D’Aleo G, Bramanti P, Calabrò RS. Evaluating Sativex® in neuropathic pain management: a clinical and neurophysiological assessment in multiple sclerosis. Pain Med. 2016;17(6):1145-54.

42 Starowicz K, Finn D P. Cannabinoids and pain: sites and mechanisms of action. Adv Pharmacol. 2017;80:437-475.

43 Wade D T, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17(1):21-9.

44 Hansen JS, Hansen RM, Petersen T, Gustavsen S, Oturai AB, Sellebjerg F, Sædder EA, Kasch H, Rasmussen P V, Finnerup NB, Svendsen KB. The effect of cannabis-based medicine on neuropathic pain and spasticity in patients with multiple sclerosis and spinal cord injury: study protocol of a national multicenter double-blinded, placebo-controlled trial. Brain Sci. 2021;11(9):1212.

45 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.
 


Submetido em:
01/06/2022

Aceito em:
06/03/2023

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