top of page

Medical Marijuana and Peripheral Neuropathy

Peripheral neuropathy, which is often simply referred to as neuropathy, is a condition where nerves are damaged, causing weakness, numbness and pain. Among the most common causes of neuropathy is diabetes mellitus, but the condition can also be caused by infections, alcoholism, traumatic injuries, autoimmune diseases, medications, infections, tumors, and inherited disorders.

The symptoms associated with neuropathy depend on what types of nerves are damaged. Damage to sensory nerves, which receive sensation and damage, can cause tingling and stabbing or burning pain. Damage to motor nerves, which control how the muscles move, can cause muscle weakness and a lack of coordination. If damage occurs in autonomic nerves, which control functions like blood pressure, heart rate, digestion, and bladder processes, an individual can experience heat intolerance, bowel and bladder problems, digestive issues and changes in blood pressure. Neuropathy can also increase the risk of infection and burns and other skin traumas because one may not realize they’re injured or feel temperature changes and pain.

Neuropathy treatment focuses on managing the underlying condition that is causing neuropathy and relieving symptoms. Medications are often used to manage pain. Transcutaneous electrical nerve stimulation (TENS), plasma exchange and intravenous immune globulin, and physical therapy can also help ease symptoms.

 

Findings: Effects of Cannabis on Peripheral Neuropathy

Cannabis has been shown to be highly effective at relieving neuropathic pain (Jensen, Chen, Furnish & Wallace, 2015) (Baron, 2015) (McDonough, McKenna, McCreary & Downer, 2014). Two major cannabinoids found in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), activate the two main cannabinoid receptors (CB1 and CB2) of the endocannabinoid system within the body (Fine & Rosenfeld, 2014). These receptors regulate the release of neurotransmitter and central nervous system immune cells to manage pain levels (Woodhams, Sagar, Burston & Chapman, 2015).

In numerous studies, cannabis has demonstrated the ability to significantly lower pain levels in patients suffering from neuropathic that had previously proven refractory to other treatments (Boychuck, Goddard, Mauro & Orellana, 2015). It’s been shown to specifically reduce neuropathic pain caused by diabetes (Wallace, et al., 2015). Multiple sclerosis and central neuropathic pain patients experienced pain relief with only mild to moderate adverse effects while undergoing two years of THC and CBD treatment (Rog, Nurmikko & Young, 2007). CBD was shown to significantly reduce neuropathic pain in cancer patients without diminishing nervous system function or adversely effecting chemotherapy effectiveness (Ward, et al., 2014). One study found that in HIV-positive patients, 94% reported an improvement in muscle pain and 90% reported an improvement in nerve pain after cannabis use (Woolridge, et al., 2005). In another study, 12 of 15 chronic pain patients who smoke herbal cannabis for therapeutic reasons reported an improvement in pain (Ware, Gamsa, Persson & Fitzcharles, 2002).

Because of cannabis’ effectiveness at reducing pain, its use is prevalent among the chronic pain population (Ware, et al., 2003). Luckily, studies indicate that long-term cannabis use for managing pain is safe. After a year of regular use, patients with chronic pain were found to be at no greater risk of serious adverse effects than non-cannabis users (Ware, et al., 2015).

​

References:

Baron, E.P. (2015, June). Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been… Headache, 55(6), 885-916. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1111/head.12570/full.

Blázquez, C., Chiarlone, A., Bellocchio, L., Resel, E., Pruunsild, P., García-Rincón, D., Sendtner, M., Timmusk, T., Lutz, B., Galve-Roperh, I., and Guzmán, M. (2015). The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway. Cell Death and Differentiation, 22(10), 1618–1629. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563779/.

Boychuck, D.G., Goddard, G., Mauro, G., and Orellana, M.F. (2015 Winter). The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. Journal of Oral & Facial Pain and Headache, 29(1), 7-14. Retrieved from https://goo.gl/R28LWD.

Campos, A.C., Fogaca, M.V., Sonegao, A.B., and Guimaraes, F.S. (2016, October). Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacological Research, 112, 119-27. Retrieved from http://www.sciencedirect.com/science/article/pii/S1043661816000396.

Castelli, M.P., Madeddu, C., Casti, A., Casu, A., Casti, P., Scherma, M., Fattore, L., Fadda, P., and  Ennas, M.G. (2014). Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity. PLoS ONE, 9(5), e98079. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028295/.

Chen, J., Lee, C.T., Errico, S., Deng, X., Cadet, J.L., and Freed, W.J. (2005). Protective effects of Δ9-tetrahydrocannabinol against N-methyl-D-aspartate-induced AF5 cell death. Brain Research. Molecular Brain Research, 134(2), 215–225. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824211/.

Dirikoc, S., Priola, S.A., Marella, M., Zsurger, N., and Chabry, J. (2007, September 5). Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. Journal of Neuroscience, 27(36), 9537-44. Retrieved from http://www.jneurosci.org/content/27/36/9537.long.

Esposito, G., Scuderi, C., Valenza, M., Togna, G. I., Latina, V., De Filippis, D., Cipriano, M., Carratu, M.R., Iuvone, T., and  Steardo, L. (2011). Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement. PLoS ONE, 6(12), e28668. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/.

Fernández-Ruiz, J., Sagredo, O., Pazos, M.R., García, C., Pertwee, R., Mechoulam, R., and Martínez-Orgado, J. (2013). Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? British Journal of Clinical Pharmacology, 75(2), 323–333. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579248/.

Fernández-Ruiz, J., Romero, J., Velasco, G., Tolon, R.M., Ramos, J.A., and Guzman, M. (2007, January). Cannabinoid CB2 receptor: a new target for controlling neural cell survival. Trends in Pharmaceutical Sciences, 28(1), 39-45. Retrieved from http://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(06)00267-7.

Fernández-Ruiz, J., Moro, M. A., & Martínez-Orgado, J. (2015). Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications. Neurotherapeutics, 12(4), 793–806. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604192/.

Fine, P.G., and Rosenfeld, M.J. (2014, October). 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.

Fishbein, M., Gov, S., Assaf, F., Gafni, M., Keren, O., and Sarne, Y. (2012, September). Long-­term behavioral and biochemical effects of an ultra-­low dose of Δ9-­tetrahydrocannabinol (THC): neuroprotection and ERK signaling. Experimental Brain Research, 221(4), 437-48. Retrieved from http://link.springer.com/article/10.1007%2Fs00221-012-3186-5.

Hamelink, C., Hampson, A., Wink, D.A., Eiden, L.E., and Eskay, R.L. (2005). Comparison of Cannabidiol, Antioxidants, and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity. The Journal of Pharmacology and Experimental Therapeutics, 314(2), 780–788. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183207/.

Hampson, A.J., Grimaldi, M., Axelrod, J., and Wink, D. (1998). Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences of the United States of America, 95(14), 8268–8273. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20965/.

Hampson, A.J., Grimaldi, M., Lolic, M., Wink, D., Rosenthal, R., and Axelrod, J. (2000). Neuroprotective antioxidants from marijuana. Annals of the New York Academy of Sciences, 899,274-82. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1749-6632.2000.tb06193.x/full.

Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M., and Izzo, A.A. (2004, April). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. Journal of Neurochemistry, 89(1), 134-41. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2003.02327.x/full.

Jensen, B., Chen, J., Furnish, T., and Wallace, M. (2015, October). Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence. Current Pain and Headache Reports, 19(10), 524. Retrieved from http://link.springer.com/article/10.1007%2Fs11916-015-0524-x.

Jiang, W., Zhang, Y., Xiao, L., Van Cleemput, J., Ji, S.P., Bai, G., and Zhang, X. (2005). Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Journal of Clinical Investigation, 115(11), 3104–3116. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253627/.

Kim, S.H., Won, S.J., Mao, X.O., Jin, K., and Greenberg, D.A. (2006, March). Molecular mechanisms of cannabinoid protection from neuronal excitotoxicity. Molecular Pharmacology, 69(30), 691-6. Retrieved from http://molpharm.aspetjournals.org/content/69/3/691.long.

Kozela, E., Lev, N., Kaushansky, N., Eilam, R., Rimmerman, N., Levy, R., Ben-Nun, A., Juknat, A., and Vogel, Z. (2011). Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. British Journal of Pharmacology, 163(7), 1507–1519. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165959/.

López Rodríguez, A.B., Siopi, E., Finn, D.P., Marchand-Leroux, C., Garcia-Segura, L.M., Jafarian-Tehrani, M.H., and Viveros, M.P. (2013). CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cerebral Cortex. Retrieved from http://cercor.oxfordjournals.org/content/early/2013/08/19/cercor.bht202.abstract.

Marsicano, G., Goodenough, S., Monory, K., Hermann, H., Eder, M., Cannich, A., Azad, S.C., Cascio, M.G., Gutiérrez, S.O., van der Stelt, M., López-Rodriguez, M.L., Casanova, E., Schütz, G., Zieglgänsberger, W., Di Marzo, V., Behl, C., and Lutz, B. (2003, October 3). CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity. Science, 302(5642), 84-8. Retrieved from http://science.sciencemag.org/content/302/5642/84/tab-pdf.

McDonough, P., McKenna, J.P., McCreary, C., and Downer, E.J. (2014, October). Neuropathic orofacial pain: cannabinoids as a therapeutic avenue. The International Journal of Biochemistry & Cell Biology, 55, 72-8. Retrieved from http://www.sciencedirect.com/science/article/pii/S1357272514002581.

Mechoulam, R., and Hanus, L. (2001). The cannabinoids: An overview. Therapeutic implications in vomiting and nausea after cancer chemotherapy, in appetite promotion, in multiple sclerosis and in neuroprotection. Pain Research and Management, 6(2), 67-73. Retrieved from http://downloads.hindawi.com/journals/prm/2001/183057.pdf.

Panikashvili, D., Simeonidou, C., Ben-Shabat, S., Hanus, L., Breuer, A., Mechoulam, R., Shohami, E. (2001, October). An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature, 413(6855), 527-31. Retrieved from http://www.nature.com/nature/journal/v413/n6855/full/413527a0.html.

Pazos, M.R., Cinquina, V., Gomez, A., Layunta, R., Santos, M., Fernandez-Ruiz, J., Martinez-Orgado, J. (2012, October). Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function. Neuropharmacology, 63(5), 776-83. Retrieved from http://www.sciencedirect.com/science/article/pii/S0028390812002328.

Pazos, M.R., Mohammed, N., Lafuente, H., Santos, M., Martinez-Pinilla, E., Moreno, E., Valdizan, E., Romero, J., Pazos, A., Franco, R., Hillard, C.J., Alvarez, F.J., Martinez-Orgado, J. (2013, August). Mechanisms of cannabidiol neuroprotection in hyopoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors. Neuropharmacology, 71, 282-91. Retrieved from http://www.sciencedirect.com/science/article/pii/S0028390813001238.

Peripheral neuropathy. (2014, December 2). Mayo Clinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/basics/definition/con-20019948.

Pope, C., Mechoulam, R., and Parsons, L. (2010). Endocannabinoid Signalling in Neurotoxicity and Neuroprotection. Neurotoxicology, 31(5), 562–571. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891218/.

Presley, C., Abidi, A., Suryawanshi, S., Mustafa, S., Meibohm, B., and Moore, B.M. (2015). Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist. Pharmacology Research & Perspectives, 3(4), e00159. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506688/.

Pryce, G., Ahmed, Z., Hankey, D.J., Jackson, S.J., Croxford, J.L. Pocock, J.M., Ledent, C., Petzold, A., Thompson, A.J., Giovannoni, G., Cuzner, M.L., and Baker, D. (2003, October). Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain, 126(Pt 10), 2191-202. Retrieved from https://academic.oup.com/brain/article/126/10/2191/314489/Cannabinoids-inhibit-neurodegeneration-in-models.

Rog, D.J., Nurmikko, T.J., and Young, C.A. (2007, September). Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clinical Therapeutics, 29(9), 2068-79. Retrieved from http://www.clinicaltherapeutics.com/article/S0149-2918(07)00294-9/.

Sagredo, O., Garcia-Arencibia, M., de Lago, E., Finetti, S., Decio, A., and Fernandez-Ruiz, J. (2007, August). Cannabinoids and Neuroprotection in Basal Ganglia Disorders. Molecular Neurobiology, 36(1), 82-91. Retrieved from http://link.springer.com/article/10.1007%2Fs12035-007-0004-3.

Scotter, E.L., Abood, M.E., and Glass, M. (2010). The endocannabinoid system as a target for the treatment of neurodegenerative disease. British Journal of Pharmacology, 160(3), 480–498. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550/.

van der Stelt, M., Veldhuis, W.B., Bar, P.R., Veldink, G.A., Vliegenthart, J.F., and Nicolay, K. (2001, September 1). Neuroprotection by Δ9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity. The Journal of Neuroscience, 21(17), 6475-9. Retrieved from http://www.jneurosci.org/content/21/17/6475.long.

Wallace, M.S., Marcotte, T.D., Umlauf, A., Gouaux, B., and Atkinson, J.H. (2015, July). Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy. Journal of Pain, 16(7), 616-27. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152762/.

Ward, S. J., McAllister, S. D., Kawamura, R., Murase, R., Neelakantan, H., & Walker, E. A. (2014). Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy. British Journal of Pharmacology, 171(3), 636–645. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969077/.

Ware, M.A., Gamsa, A., Persson, J., and Fitzcharles, M.A. (2002, Summer). Cannabis for chronic pain: case series and implications for clinicians. Pain Research & Management, 7(2), 95-9. Retrieved from http://downloads.hindawi.com/journals/prm/2002/380509.pdf.

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.ncbi.nlm.nih.gov/pubmed/26385201.

Witting, A., Chen, L., Cudaback, E., Straiker, A., Walter, L., Rickman, B., Moller, T., Brosnan, C., and Stella, N. (2006, April 18). Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. PNAS, 103(16), 6362-7. Retrieved from http://www.pnas.org/content/103/16/6362.full.

Wolf, S.A., Bick-Sander, A., Fabel, K., Leal-Galicia, P., Tauber, S., Ramirez-Rodriguez, G., Muller, A., Melnik, A., Waltinger, T.P., Ullrich, O., and Kempermann, G. (2010). Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Communication and Signaling : CCS, 8, 12. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898685/.

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.

Woolridge, E., Barton, S., Samuel, J., Osario, J., Dougherty, A., and Holdcroft, A. (2005, April). Cannabis use in HIV for pain and other medical symptoms. Journal of Pain and Symptom Management, 29(4), 358-67. Retrieved from http://www.jpsmjournal.com/article/S0885-3924(05)00063-1/fulltext.

Xapelli, S., Agasse, F., Sardà-Arroyo, L., Bernardino, L., Santos, T., Ribeiro, F.F., Valero, J., Braganca, J., Schitine, C., de Melo Reis, R.A., Sebastiao, A.M., and Malva, J.O. (2013). Activation of Type 1 Cannabinoid Receptor (CB1R) Promotes Neurogenesis in Murine Subventricular Zone Cell Cultures. PLoS ONE, 8(5), e63529. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660454/.

Zogopoulos, P., Vasileiou, I., Patsouris, E., and Theocharis, S. (2013, April). The neuroprotective role of endocannabinoids against chemical-induced injury and other adverse effects. Journal of Applied Toxicology, 33(4), 246-64. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/jat.2828/full.

​

​

bottom of page