Cited by 418Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsAdenosine and Purinergic Signaling

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Emerging role of the cannabinoid receptor CB 2 in immune regulation: therapeutic prospects for neuroinflammation

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Cabral, Guy A., Griffin-Thomas, LaToya·2009·Expert Reviews in Molecular Medicine

DOI 10.1017/s1462399409000957PMC PMC2768535

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Abstract

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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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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The Modulatory Effects and Therapeutic Potential of Cannabidiol in the Gut
Brown, K. J., Funk, K., Barrientos, A. F., Bailey, A., Shrader, S. H., Feng, W., McClain, C. J., & Song, Z. (2024) · Cells · doi:10.3390/cells13191618 · Cited by 9
“CB2 receptors have also been shown to be expressed in the brain at a much lower level and have been thought to play an important role in counteracting neuroinflammation [9,10].”
Background
Cannabis and the immune response: A comprehensive review of therapeutic potential and concerns
Barakat, M. M., Thiab, S. H., Alzaghari, L. F., Abdulrazzaq, S. B., Hasen, E., Abuarab, S. F., Nasereddin, L., Omar, A., Barakat, Y., Chellappan, D. K., et al. (2025) · Phytomedicine Plus · doi:10.1016/j.phyplu.2025.100876 · Cited by 10
The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
Surowiec, I., Gouveia-Figueira, S. C., Orikiiriza, J., Lindquist, E., Bonde, M., Magambo, J., Muhinda, C., Bergström, S., Normark, J., & Trygg, J. (2017) · Malaria Journal · doi:10.1186/s12936-017-2001-y · Cited by 8
“The endocannabinoid receptors induce immunosuppression in a wide range of immunocytes [16].”
Background
Cannabinoids for SARS-CoV-2 and is there evidence of their therapeutic efficacy?
Onay, A., Ertaş, A., Süzerer, V., Yener, İ., Yılmaz, M. A., Tilkat, E. A., Ekıncı, R., Bozhan, N., & Kandemir, S. İ. (2021) · TURKISH JOURNAL OF BIOLOGY · doi:10.3906/biy-2105-73 · Cited by 9
“…J Biol 576 lymphocytes, leukocytes, T8 lymphocytes, macrophages, mononuclear cells, microglia, mast cells, natural killer cells, and in several organs and tissues such as the brain, liver, spleen, tonsils or lymph nodes, thymus, lung, kidney (Cabral and Griffin-Thomas, 2009; Rossi et al., 2020).”
Expression and Preparation of a G‐Protein‐Coupled Cannabinoid Receptor CB2 for NMR Structural Studies
Yeliseev, A. (2019) · Current Protocols in Protein Science · doi:10.1002/cpps.83 · Cited by 9
“It is an integral membrane protein primarily found in cells of the immune and hematopoietic systems as well as in neuronal microglia (Cabral & Griffin-Thomas, 2009).”
Background
Immunology as it Pertains to Drugs of Abuse, AIDS and the Neuroimmune Axis: Mediators and Traffic
Rogers, T. J. (2010) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-010-9247-2 · Cited by 9
“…of abuse, and the capacity of these receptors to modulate immune and neuronal cell function is an important considerations for the study of drugs of abuse (Cabral and Griffin-Thomas 2009; Klein and Cabral 2006; Ferris et al. 2008; Ugen and Nyland 2006; Achur et al. 2010; Szabo and Mandrekar 2009).”
CB1 Receptor Autoradiographic Characterization of the Individual Differences in Approach and Avoidance Motivation
Laricchiuta, D., Rojo, M. L., Rodríguez‐Gaztelumendi, A., Ferlazzo, F., Petrosini, L., & Fowler, C. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042111 · Cited by 9
“Furthermore, ECS is involved in tuning behaviours mediated by reward central networks [16–18], in particular in the rewarding properties of palatable foods [19,20], as well as in physiological functions related to neuro-protection and neuro-inflammation [21,22].”
Background
Expression and NMR Structural Studies of Isotopically Labeled Cannabinoid Receptor Type II
Yeliseev, A., & Gawrisch, K. (2017) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2017.06.020 · Cited by 9
“The CB2 receptor is primarily located in cells of immune and hematopoietic systems such as thymus, spleen, and tonsil (Cabral & Griffin-Thomas, 2009).”
Inflammaging and Immunosenescence in the Post‐COVID Era: Small Molecules, Big Challenges
Francavilla, F., Intranuovo, F., Spada, G. L., Lacivita, E., Catto, M., Graps, E. A., & Altomare, C. (2024) · ChemMedChem · doi:10.1002/cmdc.202400672 · Cited by 13
Medicinal Cannabis and the Intestinal Microbiome
Vitetta, L., Nation, T. R., Oldfield, D., & Thomsen, M. (2024) · Pharmaceuticals · doi:10.3390/ph17121702 · Cited by 8
Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking
Smith, R. C., Sershen, H. W., Janowsky, D. S., Lajtha, Á., Grieco, M., Gangoiti, J. A., Gertsman, I., Johnson, W. S., Marcotte, T. D., & Davis, J. M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.887700 · Cited by 8
Does the Endocannabinoid Anandamide Affect Bacterial Quorum Sensing, Vitality, and Motility?
Friedman, L., Smoum, R., Feldman, M., Mechoulam, R., & Steinberg, D. (2019) · Cannabis and Cannabinoid Research · doi:10.1089/can.2018.0055 · Cited by 8
Social Experience Regulates Endocannabinoids Modulation of Zebrafish Motor Behaviors
Orr, S. A., Ahn, S., Park, C., Miller, T. H., Kassai, M., & Issa, F. A. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.668589 · Cited by 8
“While CB2R is mostly present on immune cells and is known to regulate immune responses and inflammatory pathways (Cabral and Griffin-Thomas, 2009; Atwood and MacKie, 2010), recent evidence suggests expression and functional effects of CB2R in the brain in regulating anxiety-like behavior and swimming activity in zebra…”
Background
Analysis of the long non-coding RNA and mRNA expression profiles associated with lidocaine-induced neurotoxicity in the spinal cord of a rat model
Zhang, Z., Jian, Y., Wu, L., Cao, Y., Li, L., Guo, Q., Wang, E., & Li, Q. (2022) · NeuroToxicology · doi:10.1016/j.neuro.2022.03.002 · Cited by 7
Prospects for cannabinoid therapies in viral encephalitis
Solbrig, M. V., Fan, Y., & Hazelton, P. R. (2013) · Brain Research · doi:10.1016/j.brainres.2013.08.032 · Cited by 8
N-Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R)
Intranuovo, F., Majellaro, M., Mastropasqua, F., Delre, P., Abatematteo, F. S., Mangiatordi, G. F., Stefanachi, A., Brea, J. M., Loza, M. I., Riganti, C., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00564 · Cited by 7
Cannabinoid Signaling Through Non-CB1R/Non-CB2R Targets in Microglia
Rimmerman, N., Kozela, E., Levy, R., Vogel, Z., & Juknat, A. (2012) · The Receptors · doi:10.1007/978-1-4614-4669-9_7 · Cited by 7
Computational Aids for Assessing Bioactivities
Wolfram, E., & Trifan, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812364-5.00010-9 · Cited by 7
Endogenous cannabinoids may regulate chronic inflammation in aspirin‐exacerbated respiratory disease
Levy, J. M. (2020) · World Journal of Otorhinolaryngology - Head and Neck Surgery · doi:10.1016/j.wjorl.2020.07.004 · Cited by 7
“Dysregulated prostaglandin synthesis is associated with chronic airway inflammation in AERD.”
BackgroundInfluential
The Neuroprotective Properties, Functions, and Roles of Cannabis sativa in Selected Diseases Related to the Nervous System
Mahdi, O., Baharuldin, M. T. H., Nor, N. H. M., Chiroma, S. M., Jagadeesan, S., & Moklas, M. A. M. (2021) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/1871524921666210127110028 · Cited by 6
Association Between Interleukin-6 and Neurocognitive Performance as a Function of Self-Reported Lifetime Marijuana Use in a Community Based Sample of African American Adults
Keen, L., & Turner, A. D. (2014) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617714000691 · Cited by 8
“In line with this notion, researchers have begun to explore the use of marijuana in the reduction of inflammatory processes (Albayram et al., 2011; Cabral & Griffin-Thomas, 2009; Jackson, Diemel, Pryce, & Baker, 2005).”
Background
Therapeutic potential of the cannabinoid receptor 2 in neuropsychiatry
García‐Gutiérrez, M. S., Navarrete, F., Gasparyan, A., & Manzanares, J. (2021) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2021.00006 · Cited by 7
Enhanced Humoral Immunity in Mice Lacking CB1 and CB2 Receptors (Cnr1 −/− /Cnr2 −/− Mice) is not Due to Increased Splenic Noradrenergic Neuronal Activity
Simkins, T., Crawford, R. B., Goudreau, J. L., Lookingland, K. J., & Kaplan, B. L. F. (2014) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-014-9549-x · Cited by 7
“CB2 is found on T cells, B cells, macrophages, and natural killer cells of the immune system, with B cells having the highest expression (Galiegue et al. 1995; Schatz et al. 1997; Cabral and Griffin-Thomas 2009).”
Background
The consequences of chronic cannabis smoking in vulnerable adolescents
Al‐Iede, M., Nunn, K. P., Milne, B., & Fitzgerald, D. A. (2016) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2016.11.001 · Cited by 7
Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury in Mice
Nicholson, G., Richards, N., Lockett, J., Ly, M., Nair, R. V., Kim, W., Vinod, K. Y., & Nagre, N. N. (2025) · Pharmaceuticals · doi:10.3390/ph18020236 · Cited by 6
“…5a). treat-ment resulted in increased HO-1 expression, while CB2R activation by HU308 reduced it (Figure Another indicator of oxidative damage is the formation of lipid peroxidation products, including 4-HNE, an unsaturated aldehyde, and a major byproduct generated during lipid peroxidation [31].”
Targeting the Endocannabinoidome: A Novel Approach to Managing Extraintestinal Complications in Inflammatory Bowel Disease
Thapa, D., Ghimire, A., Warne, L. N., & Carlessi, R. (2025) · Pharmaceuticals · doi:10.3390/ph18040478 · Cited by 6
Conformational Restriction of Designer Drugs Reveals Subtype-Selective and Biased CB2 Agonists with Neuroprotective Effects
Gioé-Gallo, C., Ortigueira, S., Prieto‐Díaz, R., Contino, M., Azuaje, J., Perrone, M. G., Riganti, C., Alberga, D., Mangiatordi, G. F., Andújar-Arias, A., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00604 · Cited by 6
Transcriptome-based analysis of blood samples reveals elevation of DNA damage response, neutrophil degranulation, cancer and neurodegenerative pathways in Plasmodium falciparum patients
Karikari, A. A., Wruck, W., & Adjaye, J. (2021) · Malaria Journal · doi:10.1186/s12936-021-03918-5 · Cited by 7
Cyclic Vomiting Syndrome and Cannabis Hyperemesis Syndrome
Lathrop, J. R., Rosen, S. N., Heitkemper, M. M., & Buchanan, D. T. (2023) · Gastroenterology Nursing · doi:10.1097/sga.0000000000000730 · Cited by 6
Medical potential of cannabis
Zielonka, D. M., Kiraga, Ł., & Kozlowski, R. M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818782-1.00012-2 · Cited by 6
Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms
Forte, D., Fanelli, F., Mezzullo, M., Barone, M., Corradi, G., Auteri, G., Bartoletti, D., Martello, M., Ottaviani, E., Terragna, C., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093399 · Cited by 6
The Endocannabinoid System and Alcohol Dependence: Will Cannabinoid Receptor 2 Agonism be More Fruitful than Cannabinoid Receptor 1 Antagonism?
Oppong‐Damoah, A., Gannon, B. M., & Murnane, K. S. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666210211115007 · Cited by 6
Hippocampal Cb2 receptors: an untold story
Visvanathar, R., Papanikolaou, M., Nôga, D. A., Pádua-Reis, M., Tort, A. B. L., & Blunder, M. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2021-0109 · Cited by 6
Chemical tools to modulate 2‐arachidonoylglycerol biosynthesis
Deng, H., & van der Stelt, M. (2017) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1568 · Cited by 6
“Activation of the CB2 receptor exerts immunosuppressive effects.[11]”
Background
Ageing, Neurodegeneration and the Endocannabinoid System
Fernández‐Ruíz, J., Sagredo, O., Gómez‐Ruíz, M., & de Lago, E. (2025) · Current topics in behavioral neurosciences · doi:10.1007/7854_2025_597 · Cited by 5
CircRNA-Based Therapeutics: a New Frontier in Neuroinflammation Treatment
Muhammed, T. M., Jasim, S. A., Uthirapathy, S., Mandaliya, V. B., Ballal, S., Kalia, R., Arya, R., Nakash, P., Mustafa, Y. F., & Ahmed, J. K. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05258-w · Cited by 5
“…MEKK1 (mitogen-activated protein kinase kinase kinase 1, or MAP3K1) expression and subsequently activates the JNK and p38 MAPK pathways, which are related to the expression of multiple pro-inflammatory cytokines and chemokines that drive microglial pro-inflammatory (M1) polarization [156, 157].”
Orally Administered CBD/CBG Hemp Extract Reduces Severity of Ulcerative Colitis and Pain in a Murine Model
Godbole, S. S., Sun, D., Coates, M. D., Himmelberger, V. J., Roopchand, D. E., & Raup‐Konsavage, W. M. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14176095 · Cited by 5
“While the CB 1 Rs are located mainly in the CNS, the CB 2 Rs are largely localized on peripheral tissues (immune and lymphatic systems), and CB 2 R activation inhibits the expression of proinflammatory cytokines, particularly IL-12 and IL-23 [28,29].”
Role of the Endocannabinoid System in Fibromyalgia
García‐Domínguez, M. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47040230 · Cited by 7
“CB 1 R was the first receptor to be identified in the rat brain [17], followed by CB 2 R, which was initially recognized in a human leukemia cell line [18] but is also expressed in lymphocytes and the spleen [19,20].”
The Role of Cannabis within an Emerging Perspective on Schizophrenia
Diviant, J. P., Vigil, J. M., & Stith, S. S. (2018) · Medicines · doi:10.3390/medicines5030086 · Cited by 5
Phytocannabinoids—Evaluation of their therapeutic role in neuroinflammation
Smith, S. L., Spurgeon, T., Spurgeon, R., & Heal, D. J. (2024) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2024.00087 · Cited by 4
Fármacos cannabinoides para las enfermedades neurológicas: ¿qué hay detrás?
Fernández‐Ruíz, J. (2012) · Revista de Neurología · doi:10.33588/rn.5410.2011689 · Cited by 5
Opportunities for Lipid-Based Probes in the Field of Immunology
Koenders, S. T. A., Gagestein, B., & van der Stelt, M. (2018) · Current topics in microbiology and immunology · doi:10.1007/82_2018_127 · Cited by 5
“While CB1 is mainly expressed within the central nervous system, CB2 is mainly expressed in immune cells and tissue (Cabral and Griffin-Thomas 2009).”
Background

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)
DOI: 10.1017/s1462399409000957
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
Licence: www.cambridge.org/core/terms (unspecified, 19 d)
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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Emerging role of the cannabinoid receptor CB 2 in immune regulation: therapeutic prospects for neuroinflammation

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