Cannabinoids as Novel Anti-Inflammatory Drugs
Open accessAbstract
Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.
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Pharmacological agents acting on various components of the endocannabinoid system exert anti-inflammatory effects, primarily through suppression of cytokine production, inhibition of cell proliferation, and induction of cell apoptosis.
“Pharmacological agents acting on various components of the endocannabinoid system exert anti-inflammatory effects, primarily through suppression of cytokine production, inhibition of cell proliferation, and induction of cell apoptosis (Nagarkatti et al, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Nagarkatti et al, 2009
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Rockwell, C. E., Snider, N. T., Thompson, J. T., Heuvel, J. P. V., & Kaminski, N. E. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.019117 · Cited by 176 · cited 2× · see citing works
“Another novel finding of this study demonstrated that WIN55,212-2 exerted its effects by acting through nuclear receptor PPAR-γ [52].”
Kimball, E. S., Schneider, C. R., Wallace, N. H., & Hornby, P. J. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00407.2005 · Cited by 173 · cited 1× · see citing works
“It has been reported that cannabinoid receptor stimulation could have a beneficial effect on experimental colitis [64].”
Smith, S. R., Terminelli, C., & Denhardt, G. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39213-4 · Cited by 170 · cited 1× · see citing works
“The results showed decreased levels of TNF-α and IL-12 but increased levels of IL-10 in the serum [29].”
The CB2 Cannabinoid Receptor Controls Myeloid Progenitor Trafficking
Palazuelos, J., Davoust, N., Julien, B., Hatterer, E., Aguado, T., Mechoulam, R., Benito, C., Romero, J., Silva, A., Guzmán, M., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m707960200 · Cited by 168 · cited 1× · see citing works
“As an explanation for the mechanism, they showed that, in the bone marrow, CB2 receptor manipulation with HU-308 increased the expression of chemokines and their receptors (CCL2, CCL3, CCL5, CCR1 and CCR2), which are important in trafficking of progenitor cells into the neuroinflamed tissue [55].”
Klein, T., Newton, C. A., Nakachi, N., & Friedman, H. P. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6461 · Cited by 159 · cited 1× · see citing works
“One of the possible mechanisms of immune control by cannabinoids during inflammation is the dys-regulation of cytokine production by immune cells and disruption of the well-regulated immune response [25].”
Maccarrone, M., Valensise, H. C. C., Bari, M., Lazzarin, N., Romaninï, C., & Finazzi‐Agrò, A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7183 · Cited by 152 · see citing works
A new strategy to block tumor growth by inhibiting endocannabinoid inactivation
Bifulco, M., Laezza, C., Valenti, M., Ligresti, A., Portella, G., & Marzo, V. D. (2004) · The FASEB Journal · doi:10.1096/fj.04-1754fje · Cited by 152 · cited 1× · see citing works
“This leads to anti-tumor effects of CB receptor signaling in various cancer types, such as thyroid, brain and prostate cancer [99–103].”
Rajesh, M., Pan, H., Mukhopadhyay, P., Bátkai, S., Osei‐Hyiaman, D., Haskó, G., Liaudet, L., Gao, B., & Pacher, P. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0307180 · Cited by 150 · cited 1× · see citing works
“It has been observed that the CB2 agonist HU-308 attenuated the hepatic ischemia/reperfusion injury by decreasing the levels of TNF-α, MIP-1α and MIP-2 in the serum and in liver homogenates [33].”
Molina‐Holgado, F., Molina‐Holgado, E., Guaza, C., & Rothwell, N. J. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10165 · Cited by 148 · cited 2× · see citing works
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Hegde, V. L., Hegde, S., Cravatt, B. F., Hofseth, L. J., Nagarkatti, M., & Nagarkatti, P. S. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.047035 · Cited by 147 · cited 1× · see citing works
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Self-citationTH2 and ‘TH2-like’ cells in allergy and asthma: pharmacological perspectives
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“Murine models of allergic airway disease, employing ovalbumin (OVA) as an aeroallergen, indicated that CD4+ Th2 cells (IL-4, IL-5 and IL-13) played a pivotal role in the pathophysiology of the allergic airway response [112].”
McKallip, R. J., Lombard, C., Martin, B. R., Nagarkatti, M., & Nagarkatti, P. S. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.033506 · Cited by 143 · cited 2× · see citing works
“The cells were incubated for 12– 24 h ex vivo and, since the phagocytosis was excluded in the cultures, we detected significant levels of THC-induced apoptosis in T cells, B cells and macrophages [17].”
Self-citationCannabidiol arrests onset of autoimmune diabetes in NOD mice
Weiss, L., Zeira, M., Reich, S., Slavin, S., Raz, I., Mechoulam, R., & Gallily, R. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.029 · Cited by 143 · cited 1× · see citing works
“A recent study indicated that treatment of 11–14-week-old female NOD mice, either in a latent diabetes stage (after 14 weeks) or with initial symptoms of diabetes (appearing up to 14 weeks) with CBD for 4 weeks, could lead to sustained inhibition of insulitis [128].”
Control by the endogenous cannabinoid system of ras oncogene‐dependent tumor growth
Bifulco, M., Laezza, C., Portella, G., Vitale, M., Orlando, P., PETROCELLIS, L. D., & Marzo, V. D. (2001) · The FASEB Journal · doi:10.1096/fj.01-0320fje · Cited by 137 · cited 1× · see citing works
“In malignancies, such as thyroid cancer, lymphoma, melanoma, pancreas and breast cancer, the levels of cannabinoid receptors are often higher in the tumor compared with normal cells of the same origin, resulting in increased sensitivity to cannabinoids in the malignancies [89,107–110].”
Role of glial K+ channels in ontogeny and gliosis: A hypothesis based upon studies on M�ller cells
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Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis
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InfluentialSumariwalla, P. F., Gallily, R., Tchilibon, S., Fride, E., Mechoulam, R., & Feldmann, M. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20050 · Cited by 134 · cited 1× · see citing works
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Correa, F., Mestre, L., Docagne, F., & Guaza, C. (2005) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706215 · Cited by 131 · cited 8× · see citing works
“The animals were then challenged with LPS.”
InfluentialCurrent Management of Pain Associated with Multiple Sclerosis
Pöllmann, W., & Feneberg, W. W. (2008) · CNS Drugs · doi:10.2165/00023210-200822040-00003 · Cited by 131 · cited 1× · see citing works
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Interleukin-6: a new therapeutic target.
Smolen, J. S., & Maini, R. N. (2006) · Arthritis Research & Therapy · doi:10.1186/ar1969 · Cited by 126 · cited 1× · see citing works
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“While the mechanisms of inflammatory liver injury are unclear, they are accompanied by infiltration of activated polymorphonuclear leukocytes, activation of Kupffer cells, production of proinflammatory cytokines and generation of ROS.”
Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes
Ghosh, S. T., Preet, A., Groopman, J. E., & Ganju, R. K. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.01.005 · Cited by 120 · cited 1× · see citing works
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Self-citationXu, H., Cheng, C. L., Chen, M., Manivannan, A., Cabay, L., Pertwee, R. G., Coutts, A. A., & Forrester, J. V. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0307159 · Cited by 116 · cited 1× · see citing works
“EAU was strongly inhibited when the CB2 was engaged and the effects of CB2 engagement appeared to be mediated predominantly through downregulation of T-cell function with a less-marked effect on antigen presentation [121].”
Cannabinoids and Multiple Sclerosis
Pertwee, R. G. (2007) · Molecular Neurobiology · doi:10.1007/s12035-007-0005-2 · Cited by 113 · cited 2× · see citing works
“In eight different clinical studies, MS patients have also reported the benefits of THC (administered via ingestion, inhalation, injection or rectal suppository), cannabis (administered via ingestion or inhalation) and the cannabinoid receptor agonist NabiloneTM, (administered via ingestion) in treating spasticity, pa…”
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Contassot, E., Tenan, M., Schnüriger, V., Pelte, M., & Dietrich, P. (2004) · Gynecologic Oncology · doi:10.1016/j.ygyno.2003.12.040 · Cited by 108 · cited 1× · see citing works
“Although the majority of the effects of cannabinoids are CB receptor mediated, AEA has been shown to induce its effects on cancerous cells by interacting with TRPV1 receptor [104,105] or cholesterol-rich lipid rafts [106].”
Molina‐Holgado, F., Molina‐Holgado, E., & Guaza, C. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00851-5 · Cited by 108 · cited 1× · see citing works
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“demonstrated that human fetal astrocytes express both CB1 and CB2 receptors and that treatment of IL-1β-stimulated astrocytes with WIN55,212-2 decreased inflammatory products including nitric oxide, TNF-α, CXCL10, CCL2 and CCL5 (Figure 1) [54].”
InfluentialDerocq, J., Jbilo, O., Bouaboula, M., Ségui, M., Clère, C., & Casellas, P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.15621 · Cited by 98 · see citing works
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“We further showed that treatment with THC caused interruption of the MAPK/ERK kinase/ERK signaling module that was required for apoptotic lethality [96,97].”
Self-citationIslam, T. C., Asplund, A. C., Lindvall, J. M., Nygren, L., Lidén, J., Kimby, E. K., Christensson, B., Smith, C. I. E., & Sander, B. (2003) · Leukemia · doi:10.1038/sj.leu.2403057 · Cited by 96 · cited 1× · see citing works
“In malignancies, such as thyroid cancer, lymphoma, melanoma, pancreas and breast cancer, the levels of cannabinoid receptors are often higher in the tumor compared with normal cells of the same origin, resulting in increased sensitivity to cannabinoids in the malignancies [89,107–110].”
Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth
DeMorrow, S., Glaser, S. S., Francis, H., Venter, J. K., Vaculin, B. T., Vaculin, S., & Alpini, G. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608238200 · Cited by 96 · cited 1× · see citing works
“Although the majority of the effects of cannabinoids are CB receptor mediated, AEA has been shown to induce its effects on cancerous cells by interacting with TRPV1 receptor [104,105] or cholesterol-rich lipid rafts [106].”
Croxford, J. L., Pryce, G., Jackson, S. J., Ledent, C. A., Giovannoni, G., Pertwee, R. G., Yamamura, T., & Baker, D. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.10.024 · Cited by 94 · cited 2× · see citing works
“In addition, caspase 3 activation was higher in knockout cultures, indicating a protective role of CB1 in neuronal cells [24].”
Kishimoto, S. (2004) · The Journal of Biochemistry · doi:10.1093/jb/mvh063 · Cited by 88 · cited 4× · see citing works
“7) Decreases TNF-α [40] THC ND Peritoneal macrophages Increases IL-1α and IL-1β [41] THC ND Human cell lines Decreases TNF-α, GM-CSF and IFN-γ, IL-10 Increases IL-8 [26] THC CB1 and CB2 independent Rat microglial cells Decreases TNF-α, IL-1α, IL-1β and IL-6 [28] In vivo WIN55,212-2 and HU-210 CB1 dependent Serum Decre…”
InfluentialA comparative study on cannabidiol-induced apoptosis in murine thymocytes and EL-4 thymoma cells
Lee, C.-Y., Wey, S., Liao, M.-H., Hsu, W., Wu, H., & Jan, T. (2008) · International Immunopharmacology · doi:10.1016/j.intimp.2008.01.018 · Cited by 85 · cited 1× · see citing works
“Cannabidiol, the nonpsychoactive ingredient in cannabis, induced apoptosis in CD4+ and CD8+ T cells at 4–8-μM concentrations by increasing reactive oxygen species (ROS) production as well as caspase 3 and 8 activity [20].”
Beta Cell Death and Protection
Mandrup-Poulsen, T. R. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1288.005 · Cited by 82 · see citing works
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“Table 2 provides a summary of the effect of cannabinoids on cytokines and chemokines in various cell models [26,28,29,32–34,37,40,41].”
Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects.
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“In general, cannabinoids are useful in treating MS because they have neuroprotective as well as immunosuppressive properties [44,45].”
Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice ☆
Jan, T., Farraj, A. K., Harkema, J. R., & Kaminski, N. E. (2003) · Toxicology and Applied Pharmacology · doi:10.1016/s0041-008x(03)00010-3 · Cited by 71 · cited 1× · see citing works
“Intraperitoneal administration of THC or cannabinol (CBN) in OVA-sensitized and challenged A/J mice led to attenuation of serum IgE, IL-2, IL-4, IL-5 and IL-13 mRNA expression and decreased allergen-induced mucus production, indicating that cannabinoidbased compounds may represent a novel class of therapeutic agents f…”
Lombard, C. A., Nagarkatti, M., & Nagarkatti, P. S. (2005) · Leukemia Research · doi:10.1016/j.leukres.2005.01.014 · Cited by 71 · cited 2× · see citing works
“Furthermore, the treatment of mice bearing a T-cell leukemia with THC could cure approximately 25% of the mice [95].”
Self-citationHypothesis: cannabinoid therapy for the treatment of gliomas?
Velasco, G., Galve‐Roperh, I., Sánchez, C., Blázquez, C., & Guzmán, M. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.04.016 · Cited by 69 · see citing works
Lu, T., Newton, C. A., Perkins, I., Friedman, H. P., & Klein, T. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.108381 · Cited by 69 · cited 5× · see citing works
“While most studies have focused on the effect of cannabinoids on cytokines, apoptosis and Th1 cell functions in the past, additional investigations on their effect on Th17 cells, DCs, NK cells, B cells and Fox-P3+ regulatory T cells is critical as such cells play an important role in the regulation and mediation of in…”
InfluentialArachidonylethanolamide Induces Apoptosis of Human Glioma Cells through Vanilloid Receptor-1
Contassot, E., Wilmotte, R., Tenan, M., Belkouch, M., Schnüriger, V., de Tribolet, N., Bourkhardt, K., & Dietrich, P. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.9.956 · Cited by 67 · cited 1× · see citing works
“Although the majority of the effects of cannabinoids are CB receptor mediated, AEA has been shown to induce its effects on cancerous cells by interacting with TRPV1 receptor [104,105] or cholesterol-rich lipid rafts [106].”
Current concepts in the pathogenesis of early rheumatoid arthritis
Pratt, A. G., Isaacs, J. D., & Mattey, D. L. (2009) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2008.08.002 · Cited by 66 · cited 3× · see citing works
“The major immune cell populations involved in joint injury are macrophages, T cells, fibroblast-like synoviocytes and DCs. Major cytokines are TNF-α and IL-1 [80,81].”
de Kozak, Y., Thillaye-Goldenberg, B., Naud, M. C., da Costa, A. V., Auriault, C., & Verwaerde, C. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01969.x · Cited by 64 · see citing works
Glutamine in parenteral nutrition: more food for thought
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“Furthermore, AjA has been shown to inhibit IL-1β production by human monocytes isolated from RA patients [82].”
Doğrul, A., Gül, H., Yıldız, O., Bilgin, F., & Güzeldemir, M. E. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.06.060 · Cited by 61 · cited 1× · see citing works
“Mice injected with a cannabis receptor agonist experienced a reduction in diabeticrelated tactile allodynia compared with nontreated controls [130].”
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“It was suggested that in this model, the autoimmune component was most effectively modulated by Δ9-THC treatment [126].”
Avraham, Y., Israeli, E., Gabbay, E., Okun, A., Zolotarev, O., Silberman, I., Ganzburg, V., Dagon, Y., Magen, I., Vorobia, L., et al. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.07.008 · Cited by 60 · cited 1× · see citing works
“Thus, influencing the endocannabinoid system with exogenous cannabinoid derivates specific for the CB1 or CB2 receptor may have a beneficial therapeutic effect on neurological dysfunction in liver diseases [78].”
Broderick, C. A., Smith, A. J., Balaggan, K. S., Georgiadis, A., Buch, P. K., Trittibach, P. C., Barker, S. E., Sarra, G., Thrasher, A. J., Dick, A. D., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.03.018 · Cited by 59 · cited 4× · see citing works
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InfluentialSánchez, A., González-Pérez, P., Galve‐Roperh, I., & García‐Merino, A. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.08.018 · Cited by 56 · cited 1× · see citing works
“demonstrated that WIN55,212-2 blocks a passive form of experimental authoimmune encephalomyelitis (EAE) by inducing apoptosis in encephalitogenic cells through partial activation of the CB2 receptor [50].”
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“This leads to anti-tumor effects of CB receptor signaling in various cancer types, such as thyroid, brain and prostate cancer [99–103].”
Zhu, W., Friedman, H. P., & Klein, T. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37693-1 · Cited by 50 · cited 2× · see citing works
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A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells
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“This leads to anti-tumor effects of CB receptor signaling in various cancer types, such as thyroid, brain and prostate cancer [99–103].”
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Bronchodilator effect of delta1‐tetrahydrocannabinol.
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“demonstrated that treatment of osteoclast-like cells with 15 and 30 μM of AjA led to induction of caspase 3 and 8 in these cells, resulting in apoptosis and protection from osteoclastogenesis [83].”
Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid
Duffen, J., Atez, F. J., Rossetti, R. G., Skulas‐Ray, A. C., Patel, R. P., & Zurier, R. B. (2007) · Rheumatology International · doi:10.1007/s00296-007-0489-0 · Cited by 36 · cited 2× · see citing works
“Recent studies showed that addition of AjA to human monocyte-derived macrophages in vitro reduced the secretion of IL-6 from activated cells, suggesting that AjA may have a value for treatment of joint inflammation in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and osteoarthritis [32].”
Ajulemic acid, a nonpsychoactive cannabinoid acid, induces apoptosis in human T lymphocytes
Bidinger, B., Torres, R., Rossetti, R. G., Brown, L., Beltre, R., BURSTEIN, S. H., Lian, J. B., Stein, G. S., & Zurier, R. B. (2003) · Clinical Immunology · doi:10.1016/s1521-6616(03)00064-0 · Cited by 33 · cited 1× · see citing works
“Ajulemic acid, a side-chain synthetic analog of Δ(8)-THC-11-oic acid, has been shown to induce apoptosis in human peripheral blood T lymphocytes via the intrinsic pathway at concentrations of 1, 3 and 10 μM [21].”
Rheumatoide Arthritis, Inflammation und Atherosklerose
H�rlimann, D., Enseleit, F., & Ruschitzka, F. T. (2004) · Herz · doi:10.1007/s00059-004-2636-7 · Cited by 32 · see citing works
de Lago, E., Gustafsson, S. B., Fernández‐Ruíz, J., Nilsson, J. A., Jacobsson, S. O. P., & Fowler, C. J. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04104.x · Cited by 27 · cited 1× · see citing works
“This leads to anti-tumor effects of CB receptor signaling in various cancer types, such as thyroid, brain and prostate cancer [99–103].”
Biecker, E., Sägesser, H., & Reichen, J. (2004) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2004.01331.x · Cited by 24 · cited 1× · see citing works
“Both CB1 and CB2 receptors have been shown to be upregulated in the early stages of liver injury [68–72].”
Potential Role of CB2 Receptors in Cannabis Smokers With Chronic Hepatitis C *
Schwabe, R. F., & Siegmund, S. V. (2005) · Hepatology · doi:10.1002/hep.20895 · Cited by 15 · cited 1× · see citing works
“The abuse of cannabis has been shown to promote liver fibrosis in patients with chronic hepatitis C, indicating that cannabinoids may exacerbate liver fibrogenesis and that CB1 receptor antagonists may play a role as anti-fibrosing molecules [71].”
Antimetastatic effect of flurbiprofen and other platelet aggregation inhibitors.
Mamytbeková, A., Řežábek, K., Kacerovská, H., Grimová, J., & Svobodová, J. (1986) · PubMed · Cited by 11 · see citing works
Bronchodîlator effect of δ1 -tetrahydrocannabinol
Hartley, J. P. R., Nogrady, S. G., Seaton, A., & Graham, J. P. P. (1978) · Abstracts · doi:10.1016/b978-0-08-023768-8.50194-8 · Cited by 4 · see citing works
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Adverse health effects of marijuana use.
Volkow, N. D., Baler, R. D., Compton, W. M., & Weiss, S. R. B. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1402309 · Cited by 2,774 · see citing works
Pellati, F., Borgonetti, V., Brighenti, V., Biagi, M., Benvenuti, S., & Corsi, L. (2018) · BioMed Research International · doi:10.1155/2018/1691428 · Cited by 375 · see citing works
Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301 · see citing works
The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases
Lowe, H., Toyang, N., Steele, B., Bryant, J., & Ngwa, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179472 · Cited by 303 · see citing works
“In addition to these neuroprotective effects, CB1R and CB2R have both demonstrated the ability to restore the BBB and even improve BBB integrity, thus further conferring protection against neurological or psychiatric diseases [165].”
BackgroundInfluentialBaron, E. P. (2018) · Headache The Journal of Head and Face Pain · doi:10.1111/head.13345 · Cited by 256 · see citing works
Vascular endothelial cell Toll-like receptor pathways in sepsis
Khakpour, S., Wilhelmsen, K., & Hellman, J. (2015) · Innate Immunity · doi:10.1177/1753425915606525 · Cited by 232 · see citing works
“Finally, recent studies suggest that another group of arachidonic acid-based lipids, the endocannabinoids, also have immunomodulatory activity.(290,300,301) The endocannabinoids are ligands for cannabinoid receptors 1 and 2 (CB1R and CB2R) and the transient receptor potential channel V1 (TRPV1).”
BackgroundCannabinoids in cancer treatment: Therapeutic potential and legislation
Dariš, B., Verboten, M. T., Knez, Ž., & Ferk, P. (2018) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2018.3532 · Cited by 219 · see citing works
The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review
Alves, V. L., Gonçalves, J. L., Aguiar, J., Teixeira, H. M., & Câmara, J. S. (2020) · Critical Reviews in Toxicology · doi:10.1080/10408444.2020.1762539 · Cited by 214 · see citing works
“JWH-018 is one among several hundred analgesic drug candidates synthesized by him (Nagarkatti et al. 2009; Preedy 2016a).”
BackgroundMarijuana Legalization: Impact on Physicians and Public Health
Wilkinson, S. T., Yarnell, S. C., Radhakrishnan, R., Ball, S. A., & D’Souza, D. C. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-050214-013454 · Cited by 198 · see citing works
“, endoscopic biopsies) were evaluated (28) Although preclinical evidence suggests a possible anti-inflammatory role of cannabinoids (23), large RCTs have not established the efficacy of marijuana in Crohn’s disease”
BackgroundThe Implications of Marijuana Legalization in Colorado
Monte, A. A., Zane, R. D., & Heard, K. J. (2014) · JAMA · doi:10.1001/jama.2014.17057 · Cited by 187 · see citing works
CNS effects of CB2 cannabinoid receptors: beyond neuro-immuno-cannabinoid activity
Onaivi, E. S., Ishiguro, H., Gu, S., & Liu, Q. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111400652 · Cited by 184 · see citing works
“…et al., 2007; FernandezRuiz et al., 2006, 2008; Jean-Gilles et al., 2010; Lunn et al., 2008; Marriott and Huffman, 2008; Murikinati et al., 2010; Nagarkatti et al., 2009; Patel et al., 2010; Rivers and Ashton, 2010; Ruiz-Valdepenas et al., 2010; Tanasescu and Constantinescu, 2010).”
BackgroundBaron, E. P., Lucas, P., Eades, J., & Hogue, O. (2018) · The Journal of Headache and Pain · doi:10.1186/s10194-018-0862-2 · Cited by 182 · see citing works
Anti-inflammatory ω-3 endocannabinoid epoxides
McDougle, D. R., Watson, J. E., Abdeen, A. A., Adili, R., Caputo, M. P., Krapf, J. E., Johnson, R. W., Kilian, K. A., Holinstat, M. A., & Das, A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610325114 · Cited by 172 · see citing works
“Consequently, there is a strong interest in the discovery of endocannabinoid derivatives that are CB2-preferring/-selective agonists as means of mitigating inflammatory pathologies (8, 36, 37).”
Ashraf, A., Clark, M., & So, P. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00065 · Cited by 158 · see citing works
“Anti-inflammatory drugs had a similar effect to chelation therapy, reversing iron-induced synaptic loss, apoptosis, and impairment of mitochondrial dynamics in rodents exposed to iron overload (Nagarkatti et al., 2009; da Silva et al., 2014; Lavich et al., 2015).”
BackgroundGiacoppo, S., Pollastro, F., Grassi, G., Bramanti, P., & Mazzon, E. (2016) · Fitoterapia · doi:10.1016/j.fitote.2016.11.010 · Cited by 149 · see citing works
“Although PI3K/Akt/mTOR pathway has been proven to be target by cannabinoids in several immune and non-immune cells [1,29], there is currently almost no data about the effects of cannabinoids in the activity of this signaling pathway in inflammatory as well as autoimmune conditions such as MS [30].”
BackgroundAl-Ghezi, Z. Z., Busbee, P. B., Alghetaa, H., Nagarkatti, P. S., & Nagarkatti, M. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.07.028 · Cited by 145 · see citing works
Self-citationBar‐Sela, G., Cohen, I., Campisi‐Pinto, S., Lewitus, G. M., Oz-Ari, L., Jehassi, A., Peer, A., Turgeman, I., Vernicova, O., Berman, P., et al. (2020) · Cancers · doi:10.3390/cancers12092447 · Cited by 137 · see citing works
“Although the anti-inflammatory effects of cannabis and phytocannabinoids have long been known [7,8], the secondary effect of cannabis on the immune system has not yet been fully elucidated.”
BackgroundHaspula, D., & Clark, M. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207693 · Cited by 137 · see citing works
Kopustinskienė, D. M., Masteiková, R., Lažauskas, R., & Bernatonienė, J. (2022) · Antioxidants · doi:10.3390/antiox11040660 · Cited by 141 · see citing works
“Cannabinoids have demonstrated strong anti-inflammatory properties in numerous in vitro and in vivo studies [1,8,70,71] (Figure 5).”
BackgroundCannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation
Wei, T.-T., Chandy, M., Nishiga, M., Zhang, A., Kumar, K. K., Thomas, D., Manhas, A., Rhee, S., Justesen, J. M., Chen, I. Y., et al. (2022) · Cell · doi:10.1016/j.cell.2022.04.005 · Cited by 133 · see citing works
Muthumalage, T., & Rahman, I. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114713 · Cited by 128 · see citing works
VanElzakker, M. B., Brumfield, S. A., & Mejia, P. S. L. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2018.01033 · Cited by 125 · see citing works
Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma
Vuolo, F. S., Abreu, S. C., Michels, M., Xisto, D. G., Blanco, N. G., Hallak, J. E. C., Zuardi, A. W., Crippa, J. A., dos Reis, C. M., Bahl, M., et al. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.11.029 · Cited by 124 · see citing works
Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype
Kozela, E., Juknat, A., Kaushansky, N., Rimmerman, N., Ben‐Nun, A., & Vogel, Z. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9493-1 · Cited by 123 · see citing works
“…hashish or marijuana) and the endocannabinoids' (eCB, i.e. anandamide and 2-arachidonoylglycerol) have been shown to exert potent anti-inflammatory activities in various experimental models of inflammation and neuroinflammatory diseases (Nagarkatti et al. 2009; Tanasescu and Constantinescu 2010).”
BackgroundThe endocannabinoid system of the skin. A potential approach for the treatment of skin disorders
del Río, C., Millán, E., García, V., Appendino, G., DeMesa, J., & Muñóz, E. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.08.022 · Cited by 119 · see citing works
Polyunsaturated fatty acids and endocannabinoids in health and disease
Freitas, H. R., Isaac, A. R., Malcher‐Lopes, R., Diaz, B. L., Trevenzoli, I. H., & Reis, R. A. D. M. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1347373 · Cited by 116 · see citing works
Hourfane, S., Mechqoq, H., Bekkali, A. Y., Rocha, J. M., & Aouad, N. E. (2023) · Plants · doi:10.3390/plants12061245 · Cited by 125 · see citing works
“Additionally, cannabinoids proved to be strong anti-inflammatory agents; in fact, they can suppress the production of pro-inflammatory cytokines and chemokines and may have therapeutic applications in health conditions underlying inflammatory components [188,189].”
BackgroundTherapeutic Potential of Cannabis: A Comprehensive Review of Current and Future Applications
Leinen, Z. J., Mohan, R., Premadasa, L. S., Acharya, A., Mohan, M., & Byrareddy, S. N. (2023) · Biomedicines · doi:10.3390/biomedicines11102630 · Cited by 114 · see citing works
Neuroinflammation and sympathetic overactivity: Mechanisms and implications in hypertension
Haspula, D., & Clark, M. A. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.01.002 · Cited by 112 · see citing works
The Anti-Inflammatory Properties of Terpenoids from Cannabis
Gallily, R., Yekhtin, Z., & Hanuš, L. O. (2018) · Cannabis and Cannabinoid Research · doi:10.1089/can.2018.0014 · Cited by 111 · see citing works
Siniscalco, D., Sapone, A., Giordano, C., Cirillo, A., de Magistris, L., Rossi, F., Fasano, A., Bradstreet, J. J., Maione, S., & Antonucci, N. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-1824-9 · Cited by 108 · see citing works
Wu, H., Huang, C., Lin, Y., Wang, C., & Jan, T. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.023 · Cited by 102 · see citing works
The role of endocannabinoids in pain modulation
Zogopoulos, P., Vasileiou, I., Patsouris, E., & Theocharis, S. E. (2013) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12008 · Cited by 106 · see citing works
Pharmacological and toxicological activities of α-humulene and its isomers: A systematic review
de Lacerda, G. M., Barbosa, M. D. O., Lopes, M. J. P., Delmondes, G. D. A., Bezerra, D. S., Araújo, I. M., de Alencar, C. D. C., Coutinho, H. D. M., Peixoto, L. R., Barbosa‐Filho, J. M., et al. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.06.049 · Cited by 103 · see citing works
Haustein, M., Ramer, R., Linnebacher, M., Manda, K., & Hinz, B. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.07.014 · Cited by 102 · see citing works
Ashraf, M. V., Khan, S., Misri, S., Gaira, K. S., Rawat, S., Rawat, B., Khan, M. A. H., Shah, A. A., Asgher, M., & Ahmad, S. (2024) · Pharmaceuticals · doi:10.3390/ph17080975 · Cited by 102 · see citing works
Cannabinoids in the Pathophysiology of Skin Inflammation
Scheau, C., Bădărău, I. A., Mihai, L.-G., Scheau, A.-E., Costache, D. O., Constantin, C., Călina, D. C., Căruntu, C., Costache, R. S., & Căruntu, A. (2020) · Molecules · doi:10.3390/molecules25030652 · Cited by 98 · see citing works
Zamberletti, E., Gabaglio, M., Woolley-Roberts, M., Bingham, S., Rubino, T., & Parolaro, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00367 · Cited by 95 · see citing works
Pulmonary effects of inhaled cannabis smoke
Tashkin, D. P., & Roth, M. D. (2019) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2019.1627366 · Cited by 94 · see citing works
Maayah, Z. H., Takahara, S., Ferdaoussi, M., & Dyck, J. R. B. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165771 · Cited by 97 · see citing works
Singh, S., Singh, T. G., Mahajan, K., & Dhiman, S. (2020) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.13326 · Cited by 94 · see citing works
The role of CB1 in immune modulation by cannabinoids
Kaplan, B. L. F. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.004 · Cited by 92 · see citing works
Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
Couch, D. G., Tasker, C., Theophilidou, E., Lund, J. N., & O’Sullivan, S. E. (2017) · Clinical Science · doi:10.1042/cs20171288 · Cited by 93 · see citing works
“It has previously been described that within the gut the CB2 receptor, AEA and 2AG are found in highest abundance within these submucosal immune and also nervous tissues such as enteric glial cells, and that this may be the primary site of endocannabinoid activation during inflammatory episodes (12,36).”
BackgroundCannabis sativa research trends, challenges, and new-age perspectives
Hussain, T., Jeena, G., Pitakbut, T., Vasilev, N. P., & Kayser, O. (2021) · iScience · doi:10.1016/j.isci.2021.103391 · Cited by 96 · see citing works
Al-Ghezi, Z. Z., Miranda, K., Nagarkatti, M., & Nagarkatti, P. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01921 · Cited by 91 · see citing works
“Cannabinoids extracted from marijuana (Cannabis sativa), as well as synthetic forms have been well-characterized for their anti-inflammatory properties (8).”
BackgroundSelf-citationPhytocannabinoids: Exploring Pharmacological Profiles and Their Impact on Therapeutical Use
Blebea, N. M., Pricopie, A. I., Vlad, R.-A., & Hancu, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084204 · Cited by 92 · see citing works
“These effects are mediated through interactions with the endocannabinoid system, which plays a crucial role in regulating immune responses and inflammation throughout the body [29].”
BackgroundA Closer Look at the Cellular and Molecular Components of the Deep/Muscular Fasciae
Fede, C., Pirri, C., Fan, C., Petrelli, L., Guidolin, D., De, R., & Stecco, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031411 · Cited by 90 · see citing works
“tory cytokines such as IL-1beta and TNF-alpha and increase anti-inflammatory cytokines, providing antifibrotic activity [58].”
BackgroundBasiouni, S., Téllez‐Isaías, G., Latorre, J. D., Graham, D. B., Petrone-García, V. M., El-Seedi, H. R., Yalçın, S., El‐Wahab, A. A., Visscher, C., May‐Simera, H., et al. (2023) · Veterinary Sciences · doi:10.3390/vetsci10010055 · Cited by 90 · see citing works
“It was shown that cannabis functions as an anti-inflammatory agent by upregulating Tregulatory cells and downregulating cytokine and chemokine release [171].”
BackgroundKip, E., & Parr‐Brownlie, L. C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101618 · Cited by 88 · see citing works
Yang, X., Hegde, V. L., Rao, R., Zhang, J., Nagarkatti, P. S., & Nagarkatti, M. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.545210 · Cited by 87 · see citing works
“These results were consistent with what was shown in our previous studies and in those of others, that exposure to THC suppresses Th1 while enhancing Th2 response (10, 40, 41).”
BackgroundResultSelf-citationInterleukin-17 in post-stroke neurodegeneration
Swardfager, W., Winer, D. A., Herrmann, N., Winer, S., & Lanctôt, K. L. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.01.021 · Cited by 85 · see citing works
Appetite problem in cancer patients: Pathophysiology, diagnosis, and treatment
Hariyanto, T. I., & Kurniawan, A. (2021) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2021.100336 · Cited by 85 · see citing works
Kozela, E., Juknat, A., Gao, F., Kaushansky, N., Coppola, G., & Vogel, Z. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0603-x · Cited by 82 · see citing works
“inflammatory effects in various models of inflammation (reviewed by [1, 2]), including T cell-mediated autoimmunity [3].”
BackgroundCannabinoids as Key Regulators of Inflammasome Signaling: A Current Perspective
Suryavanshi, S. V., Kovalchuk, I., & Kovalchuk, O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.613613 · Cited by 81 · see citing works
“Cannabinoids and cannabinoid-like compounds have proven potent anti-inflammatory and immunomodulatory properties (19, 21, 35, 51, 52).”
BackgroundVanElzakker, M. B., Brumfield, S. A., & Mejia, P. S. L. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00863 · Cited by 81 · see citing works
Krishnan, G., & Chatterjee, N. (2012) · Glia · doi:10.1002/glia.22380 · Cited by 77 · see citing works
“Multiple reports demonstrate that TNF-a, G-CSF, and IFN-g levels decrease with D9 tetrahydrocannabinol (THC), the pscychoactive compound from marijuana (Klein, 2005; Nagarkatti et al., 2009).”
BackgroundKerr, D., Harhen, B., Okine, B. N., Egan, L. J., Finn, D. P., & Roche, M. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02237.x · Cited by 77 · see citing works
“…role in modulating the immune system, representing an important therapeutic target in the treatment of both central and peripheral inflammatory disorders (see Ullrich et al., 2007; Nagarkatti et al., 2009; Stella, 2009; Finn, 2010; Jean-Gilles et al., 2010; Molina-Holgado and Molina-Holgado, 2010).”
Gaffal, E., Cron, M., Glodde, N., & Tüting, T. (2013) · Allergy · doi:10.1111/all.12183 · Cited by 76 · see citing works
“Alternative explanations for the anti-inflammatory effects of THC could be the activation of other G-protein-coupled receptors or receptorindependent effects (6).”
Background“Redundancy” of Endocannabinoid Inactivation: New Challenges and Opportunities for Pain Control
Piscitelli, F., & Marzo, V. D. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn300015x · Cited by 74 · see citing works
Vitreous biomarkers in diabetic retinopathy: A systematic review and meta-analysis
McAuley, A. K., Sanfilippo, P. G., Hewitt, A. W., Liang, H. H., Lamoureux, E. L., Wang, J. J., & Connell, P. (2013) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2013.09.010 · Cited by 74 · see citing works
Cannabinoid exposure during pregnancy and its impact on immune function
Dong, C., Chen, J., Harrington, A., Vinod, K. Y., Hegde, M. L., & Hegde, V. L. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2955-0 · Cited by 74 · see citing works
Self-citationCannabis sativa : origin and history, glandular trichome development, and cannabinoid biosynthesis
Xie, Z., Mi, Y., Kong, L., Gao, M., Chen, S., Chen, W., Meng, X., Sun, W., Chen, S., & Xu, Z. (2023) · Horticulture Research · doi:10.1093/hr/uhad150 · Cited by 78 · see citing works
“Thus, some individuals may be more prone to the effects of THC, although it also exhibits antiepileptic, antitumor, and antiemetic effects [43, 44].”
BackgroundPolyunsaturated Fatty Acid-Derived Lipid Mediators and T Cell Function
Nicolaou, A., Mauro, C., Urquhart, P., & Marelli‐Berg, F. M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00075 · Cited by 75 · see citing works
Yang, Y., Yang, H., Wang, Z., Varadaraj, K., Kumari, S. S., Mergler, S., Okada, Y., Saika, S., Kingsley, P. J., Marnett, L. J., et al. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.10.015 · Cited by 72 · see citing works
Youssif, B. G. M., Mohamed, A. M., Osman, E. E. A., Abou‐Ghadir, O. F., Elnaggar, D. H., Abdelrahman, M. H., Treamblu, L., & Gomaa, H. A. M. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.040 · Cited by 72 · see citing works
The Anti-Inflammatory Effects of Cannabidiol (CBD) on Acne
Peyravian, N., Deo, S. K., Daunert, S., & Jimenez, J. J. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s355489 · Cited by 74 · see citing works
“Mechanistically, CBD decreases inflammation and subsequent cytokine production through modulation of the immune system and suppression of immune responses.(22) We have previously reviewed the antiinflammatory and immune suppressive effects of CBD through modulation of critical signaling pathways and receptors.”
BackgroundZumbrun, E. E., Sido, J. M., Nagarkatti, P. S., & Nagarkatti, M. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9586-0 · Cited by 70 · see citing works
“Also, experimental studies have shown that marijuana cannabinoids are highly immunosuppressive (Klein et al. 1998; Klein et al. 2000; McKallip et al. 2002; Hegde et al. 2008; Nagarkatti et al. 2009; Hegde et al. 2010).”
BackgroundInfluentialSelf-citationVincent, L., Vang, D., Nguyen, J., Benson, B. A., Lei, J.-X., & Gupta, K. (2015) · Haematologica · doi:10.3324/haematol.2015.136523 · Cited by 68 · see citing works
Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis
Gazendam, A., Nucci, N. W., Gouveia, K., Khalik, H. A., Rubinger, L., & Johal, H. S. (2020) · Cannabis and Cannabinoid Research · doi:10.1089/can.2019.0079 · Cited by 68 · see citing works
Emerging Role of (Endo)Cannabinoids in Migraine
Leimuranta, P., Khiroug, L. S., & Giniatullin, R. A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00420 · Cited by 67 · see citing works
“Regarding migraine pathology, the vital characteristics justifying the proposed use of medical cannabis include anticonvulsive (Rosenberg et al., 2015), analgesic, antiemetic (Parker et al., 2011), and anti-inflammatory effects (Nagarkatti et al., 2009).”
BackgroundInfluentialSido, J. M., Yang, X., Nagarkatti, P. S., & Nagarkatti, M. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.1a1014-479r · Cited by 65 · see citing works
“The mechanisms through which THC mediates immunosuppression include apoptosis, induction of Tregs, and the induction of a switch from Th1 to Th2 phenotype [25, 26, 50].”
BackgroundSelf-citationCarter, G. T., Abood, M. E., Aggarwal, S. K., & Weiss, M. D. (2010) · American Journal of Hospice and Palliative Medicine® · doi:10.1177/1049909110369531 · Cited by 65 · see citing works
“Dense receptor concentrations are found in the cerebellum, basal ganglia, and hippocampus, likely accounting for the effect of exogenously administered cannabinoids on motor tone and coordination as well as mood state.(53-55) Low concentrations are found in the brain stem, accounting for the low potential for lethal o…”
BackgroundOssola, C. A., Surkin, P. N., Mohn, C. E., Elverdin, J. C., & Fernández‐Solari, J. (2016) · Journal of Periodontology · doi:10.1902/jop.2016.150612 · Cited by 64 · see citing works
Jackson, A. R., Nagarkatti, P. S., & Nagarkatti, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093954 · Cited by 63 · see citing works
Self-citationIndole-2-carboxamides as Allosteric Modulators of the Cannabinoid CB1 Receptor
Piscitelli, F., Ligresti, A., Regina, G. L., Coluccia, A., Morera, L., Allarà, M., Novellino, E., Marzo, V. D., & Silvestri, R. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201485c · Cited by 63 · see citing works
Costiniuk, C. T., & Jenabian, M.-A. (2019) · AIDS · doi:10.1097/qad.0000000000002345 · Cited by 63 · see citing works
“CB2 receptor activation induces apoptosis, inhibits pro-inflammatory cytokine expression, and induces a shift from a Th1 to Th2 immune response and induced myeloid-derived suppressor and T-regulatory cells [43].”
BackgroundJuknat, A., Gao, F., Coppola, G., Vogel, Z., & Kozela, E. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212039 · Cited by 63 · see citing works
Mohammed, A. K., Alghetaa, H., Zhou, J., Chatterjee, S., Nagarkatti, P. S., & Nagarkatti, M. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15226 · Cited by 63 · see citing works
“Furthermore, THC has been shown to decrease Th1 cells while promoting Tregs and MDSCs (Eisenstein & Meissler, 2015; Hegde et al., 2010; Mohammed et al., 2020; Nagarkatti et al., 2009).”
BackgroundInfluentialSelf-citationCannabigerol (CBG): A Comprehensive Review of Its Molecular Mechanisms and Therapeutic Potential
Li, S., Li, W., Malhi, N. K., Huang, J., Li, Q., Zhou, Z., Wang, R., Peng, J., Yin, T., & Wang, H. (2024) · Molecules · doi:10.3390/molecules29225471 · Cited by 63 · see citing works
“Various studies have suggested the use of cannabinoids as possible treatments for inflammatory diseases [42], such as inflammatory bowel disease (IBD) [43], liver injury [44], rheumatoid arthritis [45], and allergic asthma [46].”
Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer
Afrin, F., Chi, M., Eamens, A. L., Duchatel, R. J., Douglas, A. M., Schneider, J., Gedye, C. A., Woldu, A. S., & Dun, M. D. (2020) · Cancers · doi:10.3390/cancers12041033 · Cited by 63 · see citing works
“Thus, the involvement of CB1R is more likely to drive psychotropic activity, with the weight of evidence showing that CB2R activation modulates immunological responses [67].”
BackgroundInfluentialMastinu, A., Premoli, M., Ferrari‐Toninelli, G., Tambaro, S., Maccarinelli, G., Memo, M., & Bonini, S. A. (2018) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0013 · Cited by 60 · see citing works
Drugs and Bugs: The Gut-Brain Axis and Substance Use Disorders
Simpson, S., Mclellan, R., Wellmeyer, E., Matalon, F., & George, O. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-10022-7 · Cited by 60 · see citing works
Kozela, E., Juknat, A., Kaushansky, N., Ben‐Nun, A., Coppola, G., & Vogel, Z. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0273-0 · Cited by 59 · see citing works
“inflammatory background, including rheumatoid arthritis, experimental colitis, liver inflammation, brain injury, neurodegeneration, and multiple sclerosis (MS) (reviewed by [1,2]).”
BackgroundInfluentialMarijuana Use and Organ Transplantation: a Review and Implications for Clinical Practice
Rai, H. S., & Winder, G. S. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0843-1 · Cited by 58 · see citing works
Zamberletti, E., Gabaglio, M., Piscitelli, F., Brodie, J., Woolley-Roberts, M., Barbiero, I., Tramarin, M., Binelli, G., Landsberger, N., Kilstrup‐Nielsen, C., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119844184 · Cited by 58 · see citing works
Zhang, Z., Guo, Y., Zhang, S., Zhang, Y., Wang, Y., Ni, W., Kong, D., Chen, W., & Zheng, S. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.09.042 · Cited by 57 · see citing works
Lombard, C. A., Hegde, V. L., Nagarkatti, M., & Nagarkatti, P. S. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.181206 · Cited by 57 · see citing works
“Such studies suggest that cannabinoids may serve as a double-edged sword, on one hand exhibiting the potential to treat inflammatory diseases, while on the other hand, potentially increasing the susceptibility to cancer and infections (Nagarkatti et al., 2009; Rieder et al.; Nagarkatti et al., 2010).”
BackgroundSelf-citationThe use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review
Landa, L., Šulcová, A., & Gbelec, P. (2016) · Veterinární Medicína · doi:10.17221/8762-vetmed · Cited by 57 · see citing works
“…the following reviews: Croxford (2003), Guzman (2003), Croxford and Yamamura (2005), Mendizabal and AdlerGraschinsky (2007), Sarfaraz et al. (2008), Nagarkatti et al. (2009), Steffens and Pacher (2012), Velasco et al. (2012), Han et al. (2013), Massi (2013), Stanley et al. (2013), Kucerova et al.…”
BackgroundRao, R., Nagarkatti, P. S., & Nagarkatti, M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.13026 · Cited by 55 · see citing works
“Δ(9)-Tetrahydrocannabinol (THC) is a marijuana plantderived cannabinoid known for its robust anti-inflammatory and immunosuppressive properties (Klein, 2005; Nagarkatti et al., 2009; 2010).”
BackgroundSelf-citationWilhelmsen, K., Khakpour, S., Tran, A., Sheehan, K., Schumacher, M. A., Xu, F., & Hellman, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.536953 · Cited by 55 · see citing works
“NADA and WIN55,212-2 Negatively Regulate EC Inflammatory Activation—Cannabinoids have been reported to modulate the inflammatory activation of leukocytes, but their effects on endothelial inflammation have not been thoroughly investigated (16, 17).”
BackgroundNeuroinflammation and neuroprogression in depression: Effects of alternative drug treatments
Richardson, B., MacPherson, A., & Bambico, F. R. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100554 · Cited by 56 · see citing works
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“CBD has also demonstrated anti-inflammatory [22,23], anti-oxidative and wound healing effects [24–27].”
BackgroundFujii, M., Sherchan, P., Krafft, P. R., Rolland, W. B., Soejima, Y., & Zhang, J. H. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.04.034 · Cited by 49 · see citing works
“The cannabinoid type 1 receptor (CB1R) and type 2 receptor (CB2R) are wellcharacterized heterotrimeric Gi/o-protein-coupled receptors [6,7].”
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Bellocchio, L., Inchingolo, A. D., Inchingolo, A. M., Lorusso, F., Malcangi, G., Santacroce, L., Scarano, A., Bordea, I. R., Hazballa, D., D’Oria, M. T., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158329 · Cited by 66 · see citing works
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Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV
Watson, C. W., Campbell, L. M., Sun-Suslow, N., Hong, S., Umlauf, A., Ellis, R. J., Iudicello, J. E., Letendre, S. L., Marcotte, T. D., Heaton, R. K., et al. (2021) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617720001447 · Cited by 49 · see citing works
Brown, T., Sykes, D., & Allen, A. R. (2021) · Biomedicines · doi:10.3390/biomedicines9020189 · Cited by 49 · see citing works
“Cannabinoid receptors such as CB1 and CB2 are predominantly expressed in the brain and on immune cells indicating they may play a useful role in regulating inflammation [143].”
BackgroundSultan, M. A., Wilson, K. M., Abdulla, O. A., Busbee, P. B., Hall, A., Carter, T., Singh, N. P., Chatterjee, S., Nagarkatti, P. S., & Nagarkatti, M. (2021) · Cells · doi:10.3390/cells10123305 · Cited by 49 · see citing works
“Cannabinoids are compounds that activate two types of G-protein-coupled receptors, CB1 and CB2, that are expressed primarily in the CNS and cells of the immune system, respectively [15,16].”
BackgroundSelf-citation
- Authors
- Nagarkatti, P., Pandey, R., Rieder, S. A., Hegde, V. L., & Nagarkatti, M.
- Affiliations
- University of South Carolina (US)
- Venue
- Future Medicinal Chemistry
- Publisher
- Informa UK Limited
- Published
- 2009-10
- Volume
- 1
- Issue
- 7
- Pages
- 1333-1349
- ISSN
- 1756-8919 (ISSN-L)
- 1756-8927
- PMC
- PMC2828614
- OpenAlex
- W2030619237
- Cited by
- 555
- References
- 134
- Citations by year
- 2026: 35 · 2025: 40 · 2024: 51 · 2023: 46 · 2022: 54 · 2021: 98 · 2020: 58 · 2019: 46 · 2018: 31 · 2017: 15 · 2016: 14 · 2015: 21 · 2014: 15 · 2013: 11 · 2012: 13
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Future Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01AI053703, R01ES09098, R01AI058300, R01DA016545, R01HL058641 and P01AT003961)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- cannabinoids, anti-inflammatory agents, cannabinoid receptors, CB1 receptor, CB2 receptor, endocannabinoid system, immunosuppression, T cell apoptosis, dendritic cells, regulatory T cells, cytokine and chemokine production, autoimmune disease, inflammatory diseases, immune regulation
- MeSH terms
- Animals, Anti-Inflammatory Agents, Autoimmune Diseases, Cannabinoids, Humans, Immunosuppression Therapy, Models, Biological, Dronabinol, Cytokines, Chemokines, Receptors, Cannabinoid, T-Lymphocytes, Regulatory, Cannabinoid Receptor Antagonists
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