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Chronic inflammation is caused by abnormal behavior in the immune system and can lead to tissue, joint and organ damage. Studies have shown marijuana is effective at reducing chronic inflammation associated with a variety of diseases and can help patients manage the pain associated with their inflammation-related condition.
Overview of Inflammation
While inflammation is an essential response by the body’s immune system to injury, bacteria and viruses, at times the inflammatory response is called upon unnecessarily. When called upon appropriately, the inflammatory response effectively removes the infectious or damaging stimuli so that the body can initiate the healing process. However, when called upon unnecessarily, in the case of autoimmune diseases, the immune system reacts as if tissues are infected or abnormal when in actuality they are normal. As a result, the body causes damage to its own tissues.
Acute inflammation that comes and goes as necessary to deal with injuries and diseases represents a well-balanced and effective immune system. With chronic inflammation, however, the immune system is essentially “out-of-wack” as it won’t shut off the inflammatory response.
Examples of diseases that are associated with inflammation include rheumatoid arthritis, a chronic inflammatory disease that causes joint destruction, deformity and loss of function, psoriatic arthritis, which causes joint pain, stiffness and swelling, as well as red patches on the skin, Crohn’s and other inflammatory bowel diseases where the digestive tract becomes inflamed, atherosclerosis, the inflammation of arterial walls that can limit or block blood flow and cause heart attacks and stroke, and some cancers.
Treatment of inflammatory diseases typically involves anti-inflammatory and pain medications and the modifying or avoidance of particular activities that stress the inflamed area. In certain cases, surgery is required.
Findings: Effects of Cannabis on Inflammation
Medical marijuana has been found to be effective at both reducing chronic inflammation and at curtailing the pain associated with inflammatory-related diseases, thanks to its two major cannabinoids, tetrahydrocannabidiol (THC) and cannabidiol (CBD).
Both THC and CBD have demonstrated success at reducing inflammation related to a variety of conditions. Studies have shown that THC is able to reduce the development of atherosclerosis, the chronic inflammatory disease and a major risk factor of heart attacks and strokes, and at reducing airway inflammation related to the flu virus (Fimiani, et al., 1999) (Buchweitz, et al., 2008). CBD has been found to have the capability of reducing joint inflammation and has demonstrated effective at inhibiting the disease’s progression (Sumariwalla, et al., 2004) (Nagarkatti, et al., 2009). CBD has also shown to effectively reduced edema (Costa, et al., 2004). In terms of Crohn’s disease, cannabis is able to lower the digestive track inflammation and has even demonstrated it can improve the chances of reaching complete remission (Naftali, Mechulam, Lev & Konikoff, 2014) (Nagarkatti, et al., 2009). Studies also suggest that the cannabinoids in marijuana may be beneficial in certain types of cancers that are triggered by chronic inflammation (Nagarkatti, et al., 2009).
While both THC and CBD have demonstrated anti-inflammatory effectiveness, the way each goes about it varies. Both cannabinoids decrease the production and release of pro-inflammatory cytokines and decrease the activation of the LPS-induced STAT1 transcription factor, a key factor in some of the pro-inflammatory process. CBD, however, also reduces the activity of the NF-kappaB pathway, a primary pathway regulating pro-inflammatory genes, and upregulates the activation of the STAT3 transcription factor, which induces anti-inflammatory events (Kozela, et al., 2010). CBD also assists in anti-inflammation efforts by suppressing fatty acid amidohydrolase activity, which results in an increased concentration of the anti-inflammatory endocannabinoid, anandamide (Burstein & Zurier, 2009).
Inflammatory pain is a common symptom of a number of chronic inflammation diseases, such as sickle cell disease and cancer, but cannabis has proven helpful in pain management. The cannabinoids in cannabis act upon the cannabinoid receptors 1 and 2 (CB1, CB2), which are involved in the mediation of pain associated with inflammation (Clayton, Marshall, Bountra & O’Shaughnessy, 2002) (Elikottil, Gupta & Gupta, 2009). Studies have also found that CBD is effective in reducing neuropathic pain by reducing the inflammation causing sciatic nerve construction (Costa, et al., 2007).
States That Have Approved Medical Marijuana for Inflammation
Inflammation is not specifically included on the list of approved conditions for medical marijuana in any state. However, many states do include specific inflammation-related conditions. Medical marijuana is approved for patients with arthritis in Connecticut (psoriatic arthritis), California, Illinois, and New Mexico.
Patients diagnosed with Crohn’s disease are allowed to legally use marijuana for treatment in Arizona, Arkansas, Connecticut, Florida, Georgia, Hawaii, Illinois (and other irritable bowel syndromes), Louisiana, Maine (and other irritable bowel syndromes), Massachusetts, Michigan, Minnesota, Montana, New Hampshire, New Jersey (and other irritable bowel syndromes), New Mexico, New York (and other irritable bowel syndromes), North Dakota, Ohio, Pennsylvania, Rhode Island, Washington, and West Virginia. Connecticut has also approved medical marijuana to treat ulcerative colitis, another type of irritable bowel syndrome.
If an inflammation-related condition is causing chronic pain, medical marijuana has been approved for treatment in Alaska, Arizona, California, Colorado, Delaware, Hawaii, Maine, Maryland, Michigan, Montana, New Mexico, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, and West Virginia. The states of Nevada, New Hampshire, North Dakota, Montana, Ohio and Vermont allow medical marijuana to treat “severe pain.” The states of Arkansas, Minnesota, Ohio, Pennsylvania, Washington, and West Virginia have approved cannabis for the treatment of “intractable pain.”
A number of other states will consider approving medical marijuana for the treatment of other conditions, but require an approval or a recommendation by a physician. These states include: California (any debilitating illness where the medical use of marijuana has been recommended by a physician), Connecticut (other medical conditions may be approved by the Department of Consumer Protection), Massachusetts (other conditions as determined in writing by a qualifying patient’s physician), Nevada (other conditions subject to approval), Oregon (other conditions subject to approval), Rhode Island (other conditions subject to approval), and Washington (any “terminal or debilitating condition”).
In Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment.
Recent Studies on Cannabis’ effect on Inflammation
- Acharya, N., Penukonda, S., Shcheglova, T., Hagymasi, A.T., Basu, S., and Srivastava, P.K. (2017, March 27). Endocannabinoid system acts as a regulator of immune homeostasis in the gut. Proceedings of the National Academy of Sciences of the United States, 114(19), 5005-5010. Retrieved from http://www.pnas.org/content/114/19/5005.full.
- Adhikary, S., Li, H., Heller, J., Skarica, M., Zhang, M., Ganea, D., and Tuma, R.F. (2011). Modulation of Inflammatory Responses by a Cannabinoid-2–Selective Agonist after Spinal Cord Injury. Journal of Neurotrauma, 28(12), 2417–2427. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235339/.
- Alhamoruni, A., Wright, K., Larvin, M., and O’Sullivan, S. (2012). Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability. British Journal of Pharmacology, 165(8), 2598–2610. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423254/.
- Benito, C., Tolón, R.M., Pazos, M.R., Núñez, E., Castillo, A.I., and Romero, J. (2008). Cannabinoid CB2 receptors in human brain inflammation. British Journal of Pharmacology, 153(2), 277–285. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219537/.
- Booz, G.W. (2011). Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress. Free Radical Biology & Medicine, 51(5), 1054–1061. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/.
- Buchweitz, JP., Karmaus, PW., Williams, KJ., Harkema, JR. and Kaminski, NE. (2008, March). Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence of presence of Delta9-tetrahydrocannabinol. Journal of Leukocyte Biology, 83(3), 785-96. Retrieved from http://www.jleukbio.org/content/83/3/785.long.
- Burstein, S. (2015, April). Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorgaic & Medicinal Chemistry, 23(7), 1377-85. Retrieved from http://www.sciencedirect.com/science/article/pii/S0968089615000838.
- Burstein, SH. and Zurier, RB. (2009, March). Cannabinoids, endocannabinoids, and related analogs in inflammation. The AAPS Journal, 11(1), 109-19. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664885/.
- Clayton, N., Marshall, FH., Bountra, C., and O’Shaughnessy, CT. (2002, April). CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain, 96(3), 253-60. Retrieved from http://journals.lww.com/pain/pages/articleviewer.aspx?year=2002&issue=04000&article=00005&type=abstract.
- Costa, B., Colleoni, M., Conti, S., Parolaro, D., Franke, C., Trovato, AE., and Giagnoni, G. (2004, March). Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn-Schmiedeberg’s Archives of Pharmacology, 369(3), 294-9. Retrieved from http://link.springer.com/article/10.1007%2Fs00210-004-0871-3.
- Costa, B., Trovato, AE., Comelli, F., Giagnoni, G., and Colleoni, M. (2007, February). The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. European Journal of Pharmacology, 556(1-3), 75-83. Retrieved from http://www.sciencedirect.com/science/article/pii/S001429990601257X.
- Craft, R.M., Kandasamy, R., and Davis, S.M. (2013, September). Sex differences in anti-allodynic, anti-hyperalgesic and anti-edema effects of Δ9-tetrahydrocannabinol in the rat. Pain, 154(9), 1709-17. Retrieved from http://journals.lww.com/pain/pages/articleviewer.aspx?year=2013&issue=09000&article=00028&type=abstract.
- Croxford, J.L., and Yamamura, T. (2005, September). Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? Journal of Neuroimmunology, 166(1-2), 3-18. Retrieved from http://www.jni-journal.com/article/S0165-5728(05)00160-8/fulltext.
- De Filippis, D., D’Amico, A., and Iuvone, T. (2008, May). Cannabinomimetic Control of Mast Cell Mediator Release: New Perspective in Chronic Inflammation. Journal of Neuroendocrinology, 20 Suppl 1, 20-5. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2826.2008.01674.x/full.
- De Laurentiis, A., Araujo, H.A., and Rettori, V. (2014). Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation. Current Pharmaceutical Design, 20(29), 4697-706. Retrieved from http://www.eurekaselect.com/120077/article.
- De Petrocellis, L., Melck, D., Bisogno, T., and Di Marzo, V. (2000, November). Endocannabinoids and fatty acid amides in cancer inflammation and related disorders. Chemistry and Physics of Lipids, 108(1-2), 191-209. Retrieved from http://www.sciencedirect.com/science/article/pii/S0009308400001961.
- Elikkottil, J., Gupta, P. and Gupta, K. (2009, November-December). The analgesic potential of cannabinoids. Journal of Opioid Management, 5(6), 341-57. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/.
- 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/.
- Fimiani, C., Liberty, T., Aquirre, AJ., Amin, I., Ali, N. and Stefano, GB. (1999, January). Opiate, cannabinoid, and eicosanoid signaling converges on common intracellular pathways nitric oxide coupling. Prostaglandins & Other Lipid Mediators, 57(1), 23-34. Retrieved from http://www.sciencedirect.com/science/article/pii/S0090698098000689.
- Fitzcharles, M.A., McDougall, J., Ste-Marie, P.A., and Padjen, I. (2012, August). Clinical Implications for Cannabinoid Use in the Rheumatic Diseases. Arthritis and Rheumatism, 64(8), 2417-25. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/art.34522/full.
- Fukuda, S., Kohsaka, H., Takayasu, A., Yokoyama, W., Miyabe, C., Miyabe, Y., Harigai, M., Miyasaka, N., and Nanki, T. (2014). Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis. BMC Musculoskeletal Disorders, 15, 275. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243420/.
- Gallily, R., Yekhtin, Z., and Hanus, L.O. (2015, February). Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy, 6, 75-85. Retrieved from http://file.scirp.org/pdf/PP_2015021016351567.pdf.
- Hegde, V.L., Nagarkatti, P.S., and Nagarkatti, M. (2011). Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol. PLoS ONE, 6(4), e18281. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069975/.
- Iuvone, T. (2011). Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis. PLoS ONE, 6(12), e28159. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/.
- Jamontt, J., Molleman, A., Pertwee, R., and Parsons, M. (2010). The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. British Journal of Pharmacology, 160(3), 712–723. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/.
- Juknat, A., Kozela, E., Kaushansky, N., Mechoulam, R., and Vogel, Z. (2016, May). Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells. Journal of Basic and Clinical Physiology and Pharmacology, 27(3), 289-96. Retrieved from https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0071/jbcpp-2015-0071.xml.
- Kinsey, S.G., Mahadevan, A., Zhao, B., Sun, H., Naidu, P.S., Razdan, R.K., Selley, D.E., Imad Damaj, M., 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/.
- Klein, T.W. (2005, May). Cannabinoid-based drugs as anti-inflammatory therapeutics. Nature Reviews Immunology, 5, 400-411. Retrieved from http://www.nature.com/nri/journal/v5/n5/full/nri1602.html.
- Kozela, E., Pietr, M., Juknat, A., Rimmerman, N., Levy, R., and Vogel, Z. (2010). Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells. The Journal of Biological Chemistry, 285(3), 1616–1626. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/.
- Li, K., Feng, J.Y, Li, Li, Y., Yuece, B., Lin, X., Yu, L.Y., Li, Y.N., Fent, Y.J., and Storr, M. (2013, January). Anti-Inflammatory Role of Cannabidiol and O-1602 in Cerulein-Induced Acute Pancreatitis in Mice. Pancreas, 42(1), 123-129. Retrieved from http://journals.lww.com/pancreasjournal/pages/articleviewer.aspx?year=2013&issue=01000&article=00020&type=abstract.
- Matthews, A.T., and Ross, M.K. (2015). Oxyradical Stress, Endocannabinoids, and Atherosclerosis. Toxics, 3(4), 481–498. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686160/.
- Mecha, M., Feliu, A., Inigo, P.M., Mestre, L., Carrillo-Salinas, F.J., and Guaza, C. (2013, November). Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors. Neurobiology of Disease, 59, 141-50. Retrieved from http://www.sciencedirect.com/science/article/pii/S0969996113001939.
- Mechoulam, R., Sumariwalla, P.F., Feldmann, M., and Gallily, R. (2005, January). Cannabinoids in models of chronic inflammatory conditions. Phytochemistry Reviews, 4(1), 11-18. Retrieved from https://goo.gl/gnY17K.
- Michalski, C.W., Maier, M., Erkan, M., Sauliunaite, D., Bergmann, F., Pacher, P., Batkai, S., Giese, N.A., Giese, T., Friess, H., and Kleeff, J. (2008). Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells. PLoS ONE, 3(2), e1701. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2253501/.
- Naftali, T., Mechulam, R., Lev, L.B., and Konikoff, FM. (2014). Cannabis for inflammatory bowel disease. Digestive Diseases, 32(4), 468-74. Retrieved from https://www.karger.com/Article/Purchase/358155.
- Nagarkatti, P., Pandey, R., Rieder, S.A., Hegde, V.L., and Nagarkatti, M. (2009). Cannabinoids as novel anti-inflammatory drugs. Future Medicinal Chemistry, 1(7), 1333–1349. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/.
- Oláh, A., Tóth, B.I., Borbíró, I., Sugawara, K., Szöllõsi, A.G., Czifra, G., Pal, B., Ambrus, L., Kloepper, J., Camera, E., Ludovici, M., Picardo, M., Voeta, T., Zouboulis, C.C., Paus, R., and Bíró, T. (2014). Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. The Journal of Clinical Investigation, 124(9), 3713–3724. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151231/.
- Panikashvili, D., Shein, N.A., Mechoulam, R., Trembovler, V, Kohen, R., Alexandrovich, A. and Shohami, E. (2006, May). The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiology of Disease, 22(2), 257-264. Retrieved from http://www.sciencedirect.com/science/article/pii/S0969996105003074.
- Parker, J., Atez, F., Rossetti, R.G., Skulas, A., Patel, R., and Zurier, R.B. (2008, May). Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid. Rheumatology International, 28(7), 631-5. Retrieved from http://link.springer.com/article/10.1007%2Fs00296-007-0489-0.
- Rajesh, M., Mukhopadhyay, P., Bátkai, S., Patel, V., Saito, K., Matsumoto, S., Kashiwaya, Y., Horvath, B., Mukhopadhyay, B., Becker, L., Hasko, G., Liaudet, L., Wink, D.A., Veves, A., Mechoulam, R., and Pacher, P. (2010). Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology, 56(25), 2115–2125. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026637/.
- Ruhaak, L.R., Feith, J., Karlsson, P.C., Rafter, J.J., Verpoorte, R., and Bohlin, L. Evaluation of the Cyclooxygenase Inhibiting Effects of Six Major Cannabinoids Isolated from Cannabis sativa. Biological and Pharmaceutical Bulletin, 34(5), 774-8. Retrieved from https://www.jstage.jst.go.jp/article/bpb/34/5/34_5_774/_pdf.
- Ruiz-Valdepeñas, L., Martínez-Orgado, J.A., Benito, C., Millán, Á., Tolón, R.M., and Romero, J. (2011). Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study. Journal of Neuroinflammation, 8, 5. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034694/.
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