Cannabinoid Receptor 2: Potential Role in Immunomodulation and Neuroinflammation.

Department of Pathology and Laboratory Medicine, Temple University School of Medicine, 3401 N. Broad St., Philadelphia, PA, 19140, USA, .
Journal of Neuroimmune Pharmacology (Impact Factor: 3.8). 03/2013; DOI: 10.1007/s11481-013-9445-9
Source: PubMed

ABSTRACT An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB1, CB2) play a significant role in physiologic and pathologic processes, including cognitive and immune functions. While the addictive properties of marijuana, an extract from the Cannabis plant, are well recognized, there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer's disease to name a few), mainly mediated by CB2 activation. Development of CB2 agonists as therapeutic agents has been hampered by the complexity of their intracellular signaling, relative paucity of highly selective compounds and insufficient data regarding end effects in the target cells and organs. This review attempts to summarize recent advances in studies of CB2 activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection. The blood-brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention. Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cell death (CB1), inflammation (CB2) and oxidative stress (possibly CB-independent) - all processes that also damage the BBB. Several examples of CB-mediated protection of the BBB have been found, such as inhibition of leukocyte influx and induction of amyloid beta efflux across the BBB. Moreover, the CB receptors were shown to improve BBB integrity, particularly by restoring the tightness of the tight junctions. This review demonstrated that both CB receptors are able to restore the BBB and neuroprotection, but much uncertainty about the underlying signalling cascades still exists and further investigation is needed.
    NeuroMolecular Medicine 09/2014; · 3.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; ∆9-THC Dronabinol). Previously, we demonstrated that chronic ∆9-THC administration decreases early mortality in male SIV-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either ∆9-THC (0.18 - 0.32 mg/kg, intramuscular, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic ∆9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by ∆9-THC compared to control females; however, females that received chronic ∆9-THC did not gain as much weight as control animals. In addition, ∆9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic ∆9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic ∆9-THC in males versus females remain to be explained, but highlight the need of further studies to explore the sex-dependent effects of ∆9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission.
    AIDS research and human retroviruses. 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Common pharmacological treatments of neuropathic and chronic inflammatory pain conditions generally lack efficacy and/or are associated with significant untoward side effects. However, recent preclinical data indicate that combined inhibition of cyclooxygenase (COX) and fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of the endocannabinoid N- arachidonoylethanolamine (anandamide; AEA), produces enhanced antinociceptive effects in a variety of murine models of pain. Accordingly, the primary objective of the present study was to investigate the consequences of co-administration of the COX inhibitor diclofenac and the highly selective FAAH inhibitor PF-3845 in models of neuropathic pain (i.e., chronic constrictive injury of the sciatic nerve (CCI)) and inflammatory pain induced by an intraplantar injection of carrageenan. Here, we report that combined administration of subthreshold doses of these drugs produced enhanced antinociceptive effects in CCI and carrageenan pain models, the latter of which was demonstrated to require both CB1 and CB2 receptors. The combined administration of subthreshold doses of these drugs also increased AEA levels and decreased prostaglandin levels in whole brain. Together, these data add to the growing research that dual blockade of FAAH and COX represents a potential therapeutic strategy for the treatment of neuropathic and inflammatory pain states.
    Pharmacology Biochemistry and Behavior 07/2014; · 2.82 Impact Factor


Available from
May 27, 2014