Dor – Pesquisas com canabinoides

Estudos indicam que a canabis diminui as dores de pacientes diagnosticados com dor neuropática e nociceptiva, mostrando ainda que ela é eficaz no controle de dores resistentes a outros tratamentos tradicionais. Pesquisas sugerem ainda que a canabis poderia mitigar a crise dos analgésicos opioides, reduzindo dores e o desejo descontrolado por essas substâncias 17.

A dor é uma sensação desconfortável – alfinetada, formigamento, queimação, ferroada – que se manifesta depois de um ferimento, doença ou relacionada a um problema crônico de saúde. Dores podem limitar a produtividade e afetar o bem-estar de um indivíduo. Os custos associados ao tratamento de dores nos Estados Unidos fica entre US$560 e US$635 bilhões por ano 16.

A dor é comumente classificada como aguda ou crônica. A dor aguda aparece como resultado de um evento traumático e normalmente desaparece depois que sua causa é identificada e tratada. Já a dor crônica é um desconforto que se desenvolve em decorrência de uma doença crônica, como a artrite ou síndrome do intestino irritável. É comum dores crônicas persistirem por longos períodos de tempo e resistirem a uma variedade de tratamentos médicos.

Descobertas: efeitos da canabis no tratamento de dor

O volume de estudos que apoia a eficácia da canabis como analgésico é muito grande. Os principais canabinoides encontrados na planta têm sido considerados eficazes na diminuição dos níveis de dor em uma série de condições clínicas 3,6,10,12,17,18,19,21,22,23,24,25,26. Recentemente, uma pesquisa com usuários de canabis medicinal descobriu que a planta oferece uma redução média de 64% nas dores 24.

Acredita-se que os canabinoides conseguem reduzir a dor através de sua interação com o sistema endocanabinoide, uma rede reguladora que mantém as funções vitais em equilíbrio. Os canabinoides interagem com os dois principais receptores canabinoides (CB1 e CB2) do sistema endocanabinoide, que ajusta a liberação de neurotransmissores em um esforço para controlar os níveis de dor 4,5,8,13,15.

Estudos têm demonstrado a segurança do uso de canabis no controle de dores 23. Com o alto risco de abuso de medicamentos analgésicos, que tiram a vida de mais de 40 pacientes por dia só nos EUA, estudos sugerem que a canabis poderia ser uma forma não viciante de tratar dores crônicas 1. Mais recentemente, pesquisadores descobriram que a canabis vaporizada contendo THC causou uma “resposta analgésica significativa” em um estudo clínico envolvendo 42 pacientes que não obtiveram uma reação eficaz com medicamentos analgésicos convencionais de origem opioide e outros fármacos anti-inflamatórios não-esteroidais (NSAID) 26.

Referências:

  1. About the Epidemic. (n.d.). U.S. Department of Health & Human Services. Retrieved from
    https://www.hhs.gov/opioids/about-the-epidemic/.
  2. Abrams, D.I., Couey, P., Shade, S.B., Kelly, M.E., and Benowitz, N.L. (2011, December). Cannabinoid–Opioid Interaction in Chronic Pain. Clinical Pharmacology & Therapeutics, 90(6), 844-51. Retrieved from
    http://onlinelibrary.wiley.com/wol1/doi/10.1038/clpt.2011.188/full    .
  3. Borgelt, L.M., Franson, K.L., Nussbaum, A.M., Wang, G.S. (2013, February). The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy, 33(2), 195-209. Retrieved from
    http://onlinelibrary.wiley.com/wol1/doi/10.1002/phar.1187/full.
  4. Bosshard, S.C., Grandjean, J., Schroeter, A., Baltes, C., Zeilhofer, H.U., and Rudin, M. (2012, July). Hyperalgesia by low doses of the local anesthetic lidocaine involves cannabinoid signaling: An fMRI study in mice. Pain, 153(7), 1450-8. Retrieved from
    http://journals.lww.com/pain/pages/articleviewer.aspx?year=2012&issue=07000&article=00019&type=abstract.
  5. Burston, J.J., Sager, D.R., Shao, P., Bai, M., King, E., Brailsford, L., Turner, J.M., Hathway, G.J., Bennett, A.J., Walsh, D.A., Kendall, D.A., Lichtman, A., and Chapman, V. (2013, November 25). Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint. PLOS One, 8(11), e80440. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840025/.
  6. Carlini, B.H., Garrett, S.B., and Carter, G.T. (2015, September). Medicinal Cannabis: A Survey Among Health Care Providers in Washington State. The American Journal of Hospice & Palliative Care. Retrieved from
    http://journals.sagepub.com/doi/pdf/10.1177/1049909115604669.
  7. Cottler, L. B., Abdallah, A. B., Cummings, S. M., Barr, J., Banks, R., & Forchheimer, R. (2011). Injury, Pain, and Prescription Opioid Use Among Former National Football League (NFL) Players. Drug and Alcohol Dependence, 116(1-3), 188–194. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095672/.
  8. Cravatt, B.F., and Lichtman, A.H. (2004, October). The endogenous cannabinoid system and its role in nociceptive behavior. Journal of Neurobiology, 61(1), 149-60. Retrieved from
    http://onlinelibrary.wiley.com/doi/10.1002/neu.20080/epdf.
  9. Emerich, B.L., Ferreira, R.C.M., Cordeiro, M.N., Borges, M.H., Pimenta, A.M.C., Figueiredo, S.G., Duarte, I.D.G., and de Lima, M.E. (2016). δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats. Toxins, 8(4), 106. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848632/.
  10. Fine, P.G., and Rosenfeld, M.J. (2014). Cannabinoids for Neuropathic Pain. Current Pain and Headache Reports, 18(10), 451. Retrieved from
    http://link.springer.com/article/10.1007%2Fs11916-014-0451-2.
  11. Gerak, L.R., and France, C.P. (2016, May). Combined treatment with morphine and Δ9-tetrahydrocannibinol (THC) in rhesus monkeys: antinociceptive tolerance and withdrawal. The Journal of Pharmacology and Experimental Therapeutics, 357(2), 357-66. Retrieved from
    http://jpet.aspetjournals.org/content/357/2/357.long.
  12. Hirsh, A.T., Kratz, A.L., Engel, J.M., and Jensen, M.P. (2011). Survey Results of Pain Treatments in Adults with Cerebral Palsy. American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists, 90(3), 207–216. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036542/.
  13. Kinsey, S.G., Mahadevan, A., Zhao, B., Sun, H., Naidu, P. S., Razdan, R.K., Selley, D.E., Damaj, M.I., and Lichtman, A.H. (2011). The CB2 cannabinoid receptor-selective agonist O-3223 reduces pain and inflammation without apparent cannabinoid behavioral effects. Neuropharmacology, 60(2-3), 244–251. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021987/    .
  14. Lee, M.C., Ploner, M., Wiech, K., Bingel, Ul, Wanigasekera, V., Brooks, J., Menon, D.K., and Tracey, I. (2013, January). Amygdala activity contributes to the dissociative effect of cannabis on pain perception. Pain, 154(1), 124-134. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549497/    .
  15. Li, M.H., Suchland, K.L., and Ingram, S. (2016, December). Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain. Journal of Neuroscience, 1310-16. Retrieved from
    http://www.jneurosci.org/content/early/2016/12/09/JNEUROSCI.1310-16.2016.1    .
  16. Pain: Hope Through Research (2015, September 4). National Institute of Neurological Disorders and Stroke. Retrieved from
    https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Pain-Hope-Through-Research    .
  17. Perron, B.E., Bohnert, K., Perone, A.K., Bonn-Miller, M.O., & Ilgen, M. (2015). Use of Prescription Pain Medications Among Medical Cannabis Patients: Comparisons of Pain Levels, Functioning, and Patterns of Alcohol and Other Drug Use. Journal of Studies on Alcohol and Drugs, 76(3), 406–413. Retrieved fromhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440298/.
  18. Roberts, J.D., Gennings, C., and Shih, M. (2006, January). Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine. European Journal of Pharmacology, 530(1-2), 54-8. Retrieved from
    http://www.sciencedirect.com/science/article/pii/S001429990501215X    .
  19. Russo, E.B., and Hohmann, A.G. (2012, September 22). Role of cannabinoids in pain management. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches, 181-197. Retrieved from
    http://link.springer.com/chapter/10.1007%2F978-1-4614-1560-2_18.
  20. Staahl, C., Olesen, A.E., Andresen, T., Arendt-Nielsen, L., and Drewes, A.M. (2009, September). Assessing efficacy of non-opioid analgesics in experimental pain models in healthy volunteers- an updated review. British Pharmacological Society, 68(3), 322-341. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766472/    .
  21. Wakley, A.A., Wiley, J.L., and Craft, RM. (2014). Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat. Drug and Alcohol Dependence, 143, 22–28. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161674/    .
  22. Ware, M.A., Doyle, C.R., Woods, R., Lynch, M.E., and Clark, A.J. (2003, March). Cannabis use for chronic non-cancer pain: results of a prospective survey. Pain, 102(1-2). Retrieved from
    http://journals.lww.com/pain/Abstract/2003/03000/Cannabis_use_for_chronic_non_cancer_pain__results.23.aspx.
  23. Ware, M.A., Wang, T., Shapiro, S., and Collet, J.P. (2015, September 15). Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). The Journal of Pain. Retrieved from
    http://www.jpain.org/article/S1526-5900(15)00837-8/fulltext    .
  24. Webb, C. W., & Webb, S. M. (2014). Therapeutic Benefits of Cannabis: A Patient Survey. Hawai’i Journal of Medicine & Public Health, 73(4), 109–111. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998228/.
  25. Wilsey, B., Marcotte, T. D., Deutsch, R., Gouaux, B., Sakai, S., & Donaghe, H. (2013). Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain. The Journal of Pain : Official Journal of the American Pain Society, 14(2), 136–148. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566631/.
  26. Wilsey, B., Marcotte, T.D., Deutsch, R., Zhao, H., Prasad, H., and Phan, A. (2016) An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease. Journal of Pain, doi: 10.1016/j.pain.2016.05.010. Retrieved from
    http://www.jpain.org/article/S1526-5900(16)30072-4/fulltext    .
  27. Woodhams, S.G., Sagar, D.R., Burston, J.J., and Chapman, V. (2015). The role of the endocannabinoid system in pain. Handbook of Experimental Pharmacology, 227, 119-43. Retrieved from
    http://link.springer.com/chapter/10.1007%2F978-3-662-46450-2_7    .