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Emerging role of the cannabinoid receptor CB 2 in immune regulation: therapeutic prospects for neuroinflammation
Open accessAbstract
There is now a large body of data indicating that the cannabinoid receptor type 2 (CB 2 ) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB 2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB 2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB 2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.
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“Endocannabinoids mediate inflammation by regulating cytokines at different steps throughout the inflammatory response (Cabral and Griffin-Thomas, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Cabral and Griffin-Thomas, 2009
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“For example, THC and AEA suppress proinflammatory cytokines and enhance anti-inflammatory cytokines in both innate and adaptive immune responses (Cabral and Griffin-Thomas, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Cabral and Griffin-Thomas, 2009
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“Cannabinoids also inhibit the cell-specific proliferation of B and T cells (Cabral and Griffin-Thomas, 2009;Klein and Cabral, 2006).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Cabral and Griffin-Thomas, 2009
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Research works printed but not linked: 4
- http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=105400 (amyotrophic lateral sclerosis)
- http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114610 (CB1)
- http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605051 (CB2) The National Institute of Drug Abuse website includes listings of clinical trials:
- http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126200 (multiple sclerosis)
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“…mentioned, the CB2 receptors are found throughout the immune system including on B lymphocytes, natural killer cells, macrophages, monocytes, microglia, and T lymphocytes, making these receptors the primary component of the ECS involved in inflammation (Cabral and Griffin-Thomas 2009; Crowe et al.”
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Zhu, Y. F., Linher‐Melville, K., Wu, J., Fazzari, J., Miladinovic, T., Ungard, R. G., Zhu, K. L., & Singh, G. (2020) · Molecular Pain · doi:10.1177/1744806920911536 · Cited by 26
Marini, P., Cascio, M. G., King, A. W. T., Pertwee, R. G., & Ross, R. A. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12191 · Cited by 26
“On the other hand, the CB2 receptor is expressed mainly in the cells and tissues of the immune system including thymus, tonsils, B and T cells, macrophages, monocytes and NK cells and, to a far lesser extent, in brain (Van Sickle et al., 2005; Cabral and Griffin-Thomas, 2009).”
BackgroundMartella, A., Sijben, H. J., Rufer, A. C., Grether, U., Fingerle, J., Ullmer, C., Härtung, T., IJzerman, A. P., van der Stelt, M., & Heitman, L. H. (2017) · Molecular Pharmacology · doi:10.1124/mol.117.108605 · Cited by 26
“Finally, in light of the high and dynamic endocannabinoid tone in healthy states—and especially in diseased states (Cabral and Griffin-Thomas, 2009)—the characterization of the kinetic binding behavior of these endogenous ligands can reveal important insights about the physiology of these lipid…”
BackgroundAnalysis of natural product regulation of cannabinoid receptors in the treatment of human disease
Badal, S. A. M., Smith, K. N., & Rajnarayanan, R. V. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.06.003 · Cited by 27
Holloman, B. L., Nagarkatti, M., & Nagarkatti, P. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147302 · Cited by 27
“Additionally, the binding of THC to the CB2 receptor induces immunomodulatory and immunosuppressive effects by decreasing cAMP production [36,65,66].”
BackgroundSomvanshi, R. K., Zou, S., Kadhim, S., Padania, S., Hsu, E., & Kumar, U. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166325 · Cited by 25
Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury
Fernández‐López, D., Lizasoaín, I., Moro, M. Á., & Martínez-Orgado, J. A. (2013) · Brain Sciences · doi:10.3390/brainsci3031043 · Cited by 25
“The intrinsic capability of the endocannabinoid system of inhibiting synaptic transmission and immune responses has arisen the interest on cannabinoids as therapeutic molecules for the prevention and treatment of CNS pathologies with an important neuroinflammatory component [58], being several manifestations of perina…”
BackgroundImaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review
Woodcock, E. A., Hillmer, A. T., Mason, G. F., & Cosgrove, K. (2019) · Complex Psychiatry · doi:10.1159/000499621 · Cited by 27
Vasincu, A., Rusu, R.-N., Ababei, D. C., Neamţu, M., Arcan, O. D., Macadan, I., Chiriac, S. I. B., Bild, W., & Bild, V. (2023) · Biomedicines · doi:10.3390/biomedicines11061667 · Cited by 24
“Particularly in macrophages and macrophage-like cells, as well as CNS-resident microglia, CB2R has been shown to play a functionally significant role during the inflammatory process [91].”
InfluentialPrenatal cannabinoid exposure and altered neurotransmission
Pinky, P. D., Bloemer, J., Smith, W. D., Moore, T., Hong, H., Suppiramaniam, V. D., & Reed, M. N. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.02.018 · Cited by 26
In quest of a new therapeutic approach in COVID-19: the endocannabinoid system
LUCACIU, O. P., Aghiorghiesei, O., Petrescu, N. B., Mirică, I. C., Benea, H. R. C., & Apostu, D. (2021) · Drug Metabolism Reviews · doi:10.1080/03602532.2021.1895204 · Cited by 24
“The immune system and SARS-CoV-2 infection (Cabral and Griffin-Thomas 2009). promoted (Mamber et al. 2020; Mohammed et al. 2020) (Figure 4).”
BackgroundInfluentialCB2 Receptor Involvement in the Treatment of Substance Use Disorders
Navarrete, F., García‐Gutiérrez, M. S., Gasparyan, A., Navarro, D., & Manzanares, J. (2021) · Biomolecules · doi:10.3390/biom11111556 · Cited by 27
Maes, M. H. J., Zhou, B., Rachayon, M., Jirakran, K., Sughondhabirom, A., Sodsai, P., & Almulla, A. F. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.06.097 · Cited by 32
González, R., & Schuster (2012) · Neurobehavioral HIV Medicine · doi:10.2147/nbhiv.s17408 · Cited by 23
Effect of endocannabinoids on IgE-mediated allergic response in RBL-2H3 cells
Yoo, J., Sok, D., & Kim, M. R. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.05.013 · Cited by 24
Tapak, M., Sadeghi, S., Ghazanfari, T., & Mosaffa, N. (2023) · BMJ Open Respiratory Research · doi:10.1136/bmjresp-2022-001589 · Cited by 24
Antibacterial Effects of Phytocannabinoids
Scott, C., Agonh, D. N., & Lehmann, C. (2022) · Life · doi:10.3390/life12091394 · Cited by 23
“Additionally, CB1 inhibits N-type calcium channels through direct interaction with the inhibitory G-protein [17].”
BackgroundInfluentialFreundt-Revilla, J., Heinrich, F., Zoerner, A. A., Gesell, F. K., Beyerbach, M., Shamir, M. H., Oevermann, A., Baumgärtner, W., & Tipold, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0187197 · Cited by 24
“CB2 is detected at low levels in resting cells, while it is present at high levels in activated macrophages [5, 89].”
BackgroundInfluentialDevi, S., Zimmermann-Klemd, A. M., Fiebich, B. L., Heinrich, M., Gründemann, C., Steinberger, P., Kowarschik, S., & Huber, R. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108448 · Cited by 22
“Previous studies showed that CBD may mediate the anti-inflammatory effect on immune cells via the CB2 receptor [39,40].”
Keen, L., & Turner, A. D. (2015) · Journal of Behavioral Medicine · doi:10.1007/s10865-015-9625-6 · Cited by 23
“…novel anti-inflammatory therapies utilizing marijuana as a mitigating vector of chronic inflammation based conditions (Albayram et al., 2011; Cabral & Griffin-Thomas, 2009; Canvin & el-Gabalawy, 1999; Gorelick, 2010; Jackson, Diemel, Pryce, & Baker, 2005; Marchetti & Abbracchio, 2005; Raber…”
Wasik, A. M., Christensson, B., & Sander, B. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.10.004 · Cited by 21
“CB2 is the predominant cannabinoid eceptor in the immune system [9,10] and mice lacking CB2 have educed numbers of marginal zone B cells, CD4+ T cells and NK cells 11].”
BackgroundCannabinoids for the treatment of dementia
Marković, D., Bošnjak, D., Brković, T., Jerić, M., Rubić, Ž., Vuica, A., & Puljak, L. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012820 · Cited by 21
Boks, M. P., He, Y., Schubart, C. D., van Gastel, W. A., Elkrief, L., Huguet, G., van Eijk, K. R., Vinkers, C. H., Kahn, R. S., Paus, T., et al. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.04.051 · Cited by 21
Investigation of DNA damage, oxidative stress, and inflammation in synthetic cannabinoid users
Güler, E. M., Bektay, M. Y., Akyıldız, A. G., Sisman, B., İzzettin, F. V., & Koçyiğit, A. (2020) · Human & Experimental Toxicology · doi:10.1177/0960327120930057 · Cited by 21
Alzheimer’s disease is an inherent, natural part of human brain aging: an integrated perspective
Ferrer, I. (2022) · Free Neuropathology · doi:10.17879/freeneuropathology-2022-3806 · Cited by 25
The endocannabinoid system, a novel and key participant in acupuncture’s multiple beneficial effects
Hu, B., Bai, F., Xiong, L., & Wang, Q. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.006 · Cited by 22
“primarily in microglia (Cabral and Griffin-Thomas, 2009) and astrocytes (Stella, 2010) in the CNS, it was presumed that this CB2 receptor upregulation was probably associated with the decreased inflammatory responses that were also observed.”
InfluentialPaez, J. A., & Campillo, N. E. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180226095132 · Cited by 20
Synthesis and biological evaluation of a ring analogs of the selective CB2 inverse agonist SMM-189
Alghamdi, S. S., Mustafa, S. M., & Moore, B. M., II (2021) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2021.116035 · Cited by 18
Kimura, T., Vukoti, K., Lynch, D. L., Hurst, D. P., Grossfield, A. M., Pitman, M. C., Reggio, P. H., Yeliseev, A., & Gawrisch, K. (2013) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24411 · Cited by 19
“Structure of a beta(1)-adrenergic G-protein-coupled receptor.”
BackgroundMarsh, D. T., & Smid, S. D. (2020) · Australian Journal of Chemistry · doi:10.1071/ch20183 · Cited by 23
Greco, R., Demartini, C., Zanaboni, A., Tumelero, E., Candeloro, E., Persico, A., Morotti, A., Amantea, D., & Tassorelli, C. (2020) · Translational Stroke Research · doi:10.1007/s12975-020-00851-8 · Cited by 19
Integrating Endocannabinoid Signalling In Depression
Rana, T., Behl, T., Sehgal, A., Mehta, V., Singh, S., Kumar, R., & BUNGAU, S. G. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01774-7 · Cited by 20
The cannabinoid R(+)methanandamide induces IL-6 secretion by prostate cancer PC3 cells
Olea‐Herrero, N., Vara‐Ciruelos, D., Malagarie‐Cazenave, S., & Díaz‐Laviada, I. (2009) · Journal of Immunotoxicology · doi:10.3109/15476910903241696 · Cited by 19
“There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune responses in humans and animals, and more recently have been shown to modulate T H cell development, chemotaxis, and tumor development (Cabral and Griffin-Thomas, 2009).”
BackgroundInfluentialBioactive products from singlet oxygen photooxygenation of cannabinoids
Osman, A. G., Elokely, K. M., Yadav, V., de Carvalho, P. B., Radwan, M. M., Slade, D., Gul, W., Khan, S. I., Dale, O. R., Husni, A. S., et al. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.11.043 · Cited by 19
Metadata
- Authors
- Cabral, G. A., & Griffin-Thomas, L.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Cabral, Guy A.
- Venue
- Expert Reviews in Molecular Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2009-01
- Volume
- 11
- Pages
- e3-e3
- ISSN
- 1462-3994 (ISSN-L)
- PMC
- PMC2768535
- OpenAlex
- W2023366312
- Cited by
- 408
- References
- 190
- Citations by year
- 2026: 25 · 2025: 37 · 2024: 22 · 2023: 24 · 2022: 23 · 2021: 29 · 2020: 34 · 2019: 24 · 2018: 28 · 2017: 37 · 2016: 13 · 2015: 15 · 2014: 22 · 2013: 22 · 2012: 17
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Expert Reviews in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Cambridge
- National Institutes of Health
- National Institute on Drug Abuse (DA005832, R01DA005832, R01DA029532)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- CB2 receptor, immune regulation, neuroinflammation, signal transduction, exogenous cannabinoids, immune homeostasis, neuropathy, hyperinflammation, therapeutic target
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Inflammation, Molecular Sequence Data, Nervous System, Research, Neuroimmunomodulation, Receptor, Cannabinoid, CB2
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