Search tips
Search criteria 


Logo of currneuroLink to Publisher's site
Curr Neuropharmacol. 2012 June; 10(2): 159–166.
Published online 2012 June. doi:  10.2174/157015912800604515
PMCID: PMC3386505

Cannabinoid Modulation of Neuroinflammatory Disorders


In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ9-tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses. In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis.

Keywords: Cannabinoid receptors, Cannabinoids, Inflammation, Multiple sclerosis, Nervous system diseases, Parkinson Disease.


Cannabis sativa is a herb belonging to the Cannabaceae family, characterized by palmate leaves and numerous fibers. Its first record as a medicine dates back to 5000 years ago and it was found in China, where cannabis was used for a myriad of purposes and diseases, including malaria, neuropathic pain, nausea, sexual dysfunction and constipation [1]. The use of cannabis spread from Central Asia and deeply influenced Indian folk medicine. However, sedative and psychotropic effects of cannabis turned it into a recreational drug. This fact resulted in discrimination against the consumption of the cannabis plant and its derivatives, which delayed the scientific findings in this field.

Cannabinoid compounds may be extracted from the plant (phytocannabinoids) or be artificially obtained (synthetic cannabinoids). Mammals also produce endogenous substances (named ‘endocannabinoids’) that resemble the bioactive constituents of the plant. Since the first accurate description of a cannabis constituent in 1964 [2], enormous advances in the cannabinoid field were possible. From the discovery of Δ9-THC (THC), several phytocannabinoids were purified and identified, such as cannabidiol (CBD), cannabigerol, and cannabichromene. In the 1980s the presence of a cannabinoid receptor in the brain was identified by Devane and colleagues [3]. The high-affinity, stereoselective G protein-coupled cannabinoid receptor in the rat brain tissue was termed CB1 receptor, and soon it was cloned [4]. To CB1 receptor are attributed all psychotropic and motor impairing effects of cannabis, due to its plentiful expression in specific regions of the central nervous system (CNS) such as the hippocampus, pre-frontal cortex, basal ganglia and cerebellum [5, 6]. Also, because CB1 receptors are expressed in CNS areas related to the descending spinal inhibition, for instance, dorsal periaqueductal gray (PAG) and rostral ventrolateral medulla (RVM), they are associated to the control of pain [7-9]. In fact, synthetic THC (dronabinol) and its derivative nabilone are already marketed as therapeutic agents (Marinol® and Cesamet®, respectively) with antiemetic and analgesic properties [10-12]. Cannabinoid CB1 receptors are also found to a lower extent in peripheral tissues, including the adrenal gland, bone marrow, heart, lung, prostate, testis, thymus, tonsils, and spleen [13]. At a cellular level, CB1 receptors are found mainly at the terminals of central and peripheral neurons, where they usually modulate the release of excitatory and inhibitory neurotransmitters [14].

A second subtype of cannabinoid receptor, named CB2, was found to be expressed primarily in cells of the immune and hematopoietic systems, including myeloid, macrophage, mast, B, T, and erythroid cells [15]. Indeed, further studies on the function of this receptor identified it as the major participant in cannabinoid-mediated immune modulation [16, 17]. Additionally, the presence of CB2 in the CNS was also detected [18, 19], particularly in specific regions of the brain, spinal cord and dorsal root ganglia [20, 21]. Microglia cells, which are the CNS ‘macrophages’ and therefore can be considered as the resident immune cells of the brain, undoubtedly express CB2 receptors depending on the activated state of the cell [22-27]. Thus, microglia in healthy brain seems to not express CB2, whereas such receptors are detected in microglia from patients with neurodegenerative disorders and/or neuropathic pain [24, 28-30]. However, CB2 expression on CNS neurons is still controversial, although its presence in peripheral nociceptive neurons is responsible for modulating many types of pain [for a detailed review on this issue, see [31].

Based on the notion that an organism would not express receptors to once in life encounter their respective exogenous ligands, the existence of endogenous cannabinoid agonists needed to be considered as a fact. Thus, the first endogenous ligands (endocannabinoids) to be identified were N-arachidonoyl-ethanolamine (anandamide, AEA) and 2-arachidonylglycerol (2-AG) [32, 33], both of which are members of the eicosanoid group of cannabinoid CB1/CB2 receptor agonists. They are synthesized on demand in response to elevations of intracellular calcium levels and both function as neurotransmitters or neuromodulators, acting as retrograde synaptic messengers [34]. The biosynthetic and degradative pathways of AEA and 2-AG completed the evidence for the existence of an endocannabinoid neurotransmission system, formed by a class of receptors, its endogenous and exogenous ligands and respective metabolizing enzymes (fatty acid amide hydrolase – FAAH and monoacylglycerol lipase – MAGL), which terminate the action of endocannabinoids at the synapse [for a better review on this issue see [35, 36]. Thus, it is noteworthy to mention that endocannabinoids metabolizing enzymes constitute important targets for pharmacological interventions in order to treat/control neurodegenerative conditions as well as some types of pain [35, 37].

Synthetic analogs of phyto- and endocannabinoids have been developed to better explore the potential importance of this system for the development of therapeutic strategies in neurological disorders. These compounds include THC-like analogs and aminoalkylindole compounds typified by R-(+)-WIN55,212-2, an agonist for both CB1 and CB2 receptors. Other pharmacological tools to investigate the endocannabinoid system have been described, as selective antagonists (SR141716A (rimonabant), LY320135, SR144528) [38], inverse agonists (AM251, AM630) and as described above, inhibitors of the hydrolytic enzymes that degrade endocannabinoids (URB597, PF-750, JZL184).

Therefore, although solid efforts have been made in order to provide new insights into the biological actions of the endocannabinoid system, many questions remain yet unsolved. One of them is the possible existence of a third cannabinoid receptor, which could explain the bimodal and contradictory effects induced by cannabinoids in experimental studies. Thus, understanding the role of cannabinoids in homeostatic and/or pathological processes would favor their use as a therapeutic target for inflammatory diseases.


Due to the structure of the CB1 and CB2 receptors, they were grouped in the superfamily of G-protein coupled receptors [15]. Both receptors inhibit the adenylyl cyclase and activate mitogen-activated protein kinases (MAPKs) by signaling through Gi/o proteins. Additionally, CB1 receptors can also mediate the activation of A-type and inwardly rectifying potassium currents and inhibition of N- and P/Q-type calcium currents [14]. Unlike the CB1 subtype, CB2 receptors neither modulate the activity of P/Q-type calcium channels nor the influx of potassium [39]. Rather, intracellular CB2-dependent signaling stimulates MAPKs and phosphoinositide 3-kinase pathways, besides leading to the de novo ceramide synthesis and to the cyclooxygenase-2 (COX-2) expression [40].

It is noteworthy to mention that the receptor response to a specific cannabinoid depends on the ligand concentration, the presence of other cannabinoid ligands, the receptor density and its state of activation as well as the levels of signaling proteins [41-45]. Other cannabinoid effects may be mediated by non-CB1/CB2 receptors, as discussed elsewhere [14, 46].


The presence of both CB1 and CB2 receptors on immune cells [13], and the evidence that cannabinoids inhibit adenylyl cyclase in such cells through a pertussis toxin-sensitive mode, first suggested a role for cannabinoid receptors in the modulation of the immune system [15]. Moreover, activation of immune cells by a range of inflammatory stimuli modulates the expression of CB1 and CB2 by these cells, a fact that has been linked to the immune-regulatory effects of cannabinoids [20, 47]. In vitro experiments have reported that cannabinoids may act as immunomodulators by (1) induction of apoptosis, (2) inhibition of cell proliferation as well as cytokine and chemokine production, and (3) expansion of regulatory T cells [48, 49]. In addition, there is also evidence of endocannabinoid production as metabolites of activated immune cells [50, 51].

It has been reported that cannabinoids suppress the production of a variety of pro-inflammatory cytokines in both human cell cultures and animal models, an effect that has been thought to be mediated mainly by CB2 receptors [52, 53]. When activated, CB2 receptors can modulate immune cell migration and cytokine release both outside and within the brain [54]. Furthermore, through CB2 receptors, cannabinoids may inhibit the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and the p40 subunit of IL-12 and IL-23 by microglia and macrophages [55-57]. Moreover, CB2 receptors also seem to play an important role in regulating cell migration of neutrophils, macrophages, NK and B cells [20]. Also, it has been suggested that cannabinoids are able to decrease IL-2 production and T cells proliferation [20] and may alter the cytokine profile from a T helper (Th)1 to a Th2 phenotype in a CB2-dependent manner [53, 58]. However, CB1 receptors have also been related to neuroinflammation regulation. Notably are the data from Mestre et al. [59], showing that anandamide, through CB1 receptor activation, inhibits the expression of Theiler’s virus-induced vascular cell adhesion molecule (VCAM)-1, an endothelial receptor that plays a key role in leukocyte transmigration in multiple sclerosis [60, 61]. Zoppi et al. [62] also demonstrated that CB1 receptors activation by a synthetic selective CB1 agonist (arachidonyl-2'-chloroethylamide; ACEA) modulates stress-induced conditions and neuroinflammation by preventing the decrease in glutamate uptake and glutamate astroglial transporter excitatory amino acid transporter 2 (EAAT2) expression, the increase in pro-inflammatory molecules (cytokines, nuclear factor kappa B – NF-κB) and enzymatic sources, such as inducible nitric oxide synthase (NOS-2) and cyclooxygenase-2 (COX-2), in addition to the increase in lipid peroxidation.

Toll-like receptors (TLRs), considered as pattern recognition receptors (PRRs) that recognize molecular signatures of microbes known as pathogen-associated molecular patterns (PAMPs) have been emerged as central keys in the innate immune and neuroimmune responses [63-64]. Indeed, TLRs have been found to be expressed on glial cells and neurons [65-70]. Such receptors after being activated by PAMPs lead to intracellular signaling cascades that culminate in NF-κB translocation to the nucleus and the consequent synthesis of pro-inflammatory molecules [71]. Interestingly, as discussed above, cannabinoid receptors are also present on glial cells and a large body of evidence suggests that cannabinoids (phyto-, synthetic and endocannabinoids) can negatively modulate TLR4-induced neuroinflammation in these cells [72-76]. Moreover, as recently published by Downer et al. [77], the synthetic cannabinoid WIN-55,212-2 inhibits the pro-inflammatory signaling axis triggered by TLR3 and TLR4, while selectively augmenting TLR3-induced expression of IFN-β.

Thus, due to a myriad of neuro-protective, anti-neuro-inflammatory and anti-oxidant actions, cannabinoids have been cogitated as possible therapeutic agents for neurodegenerative disorders that combine inflammatory responses, as Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Huntington and Parkinson Diseases [78]. Hyperactive microglia, a common feature of these neurodegenerative diseases, secrete a number of pro- and anti-inflammatory cytokines, chemokines, glutamate, prostanoids, neurotrophic factors, and a range of free radicals that provide a milieu for oxidative stress. In this context, cannabidiol (CBD) has emerged as a promising strategy to treat inflammation that results from microglial hyperactivation [78], with no psychotropic side effects. Moreover, CBD has been shown to attenuate oxidative and nitrosative stress in several human disease models [78-81]. Other cannabinoid compounds that have been used in preclinical studies are exemplified in Table 11.

Table 1.
Effects of Cannabinoid Treatment for Neurodegenerative Diseases

Alzheimer’s disease (AD) is characterized by the presence of beta-amyloid (Aβ) plaques and neurofibrillary tangles in the brain, as well as cognitive decline and memory deficits. The abnormal processing of a 42-amino acid peptide (Aβ peptide) that precipitates in the extra-cellular space may be the cause of Aβ plaques accumulation, which leads to neuronal death. Activated microglia are found surrounding Aβ plaques, even before neuronal death [97]. In AD patients, increased microglial CB1 and CB2 receptor expression is found especially in plaque-bearing areas [84], suggesting a role of cannabinoids in AD pathophysiology. Eubanks et al. [82] found that THC competitively inhibits the enzyme acetylcholinesterase (AChE) by binding to the peripheral anionic site of AChE, the critical region involved in amyloidogenesis. Other studies have been conducted to support the participation of cannabinoids in AD (see Table 11).

Parkinson’s disease (PD) is a degenerative condition affecting dopaminergic neurotransmission in the basal ganglia resulting in hypokinesia [98]. Some of the neurodegenerative features of this disease include intracellular accumulation of misfolded proteins and Lewy bodies, oxidative stress, excitotoxicity, and neuroinflammation. The endocannabinoid system may be a therapeutic target because of its marked activity in the basal ganglia where it regulates neuro-transmitter release and motor activity [5, 99]. It has been demonstrated that in PD patients, endocannabinoid levels in the cerebrospinal fluid are increased [100]. As mentioned before, the use of cannabinoid drugs that activate CB1 receptors may induce motor impairment; therefore, CB1 antagonists are more suitable candidates as therapeutic agents in PD. Indeed, results drawn from preclinical studies have proposed that SR141716A may reduce the hypokinesia in an animal model of PD, at a low dose [95].

Another neurodegenerative disease involving the basal ganglia is Huntington’s disease (HD). HD has a delayed onset, defined by selective neuronal vulnerability and widespread expression of disease-related proteins during the whole lifetime. A genetic defect causes abnormal protein processing and aggregation; and cellular toxic effects involve defective autophagy-lysosomal function, transcriptional dysregulation, oxidative stress, apoptosis, mitochondrial and metabolic dysfunction [101]. HD patients develop progressive psychiatric manifestations, cognitive decline and choreiform movements [102]. In HD, there is a reduction in CB1 expression in the basal ganglia [87, 103], where the most prominent cell loss occurs. The downregulation of CB1 receptors has been thought to be a key pathogenic event in HD. Lastres-Becker and colleagues [104] found that in a rat model of HD, AEA and 2-AG levels were decreased in the striatum, while there was an increase in AEA level in the substantia nigra. These changes in endocannabinoid levels are similar to those found in the brain of HD patients. However, further studies are still necessary to clarify how cannabinoids may participate in this disorder, since many preclinical results are controversial.


One of the most promising clinical uses of cannabinoid compounds lies on the symptomatic treatment of multiple sclerosis (MS) [105], although therapies based on the expansion of regulatory T (Treg) cells have been emerged as possible targets to treat early-diagnosed autoimmune diseases [106]. MS is an autoimmune inflammatory neurodegenerative disorder characterized by nerves demyelination in the CNS. Neurological commitments mostly affect young adults (aged between 20 and 40) [16] and it is diagnosed in 30 out of 100,000 people in the world population, being women more susceptible than men. MS comprises several phenotypes (relapsing-remitting, primary progressive and secondary progressive together with less common variants) depending on the population and geographic distribution [107]. Its symptoms include weakened muscle tone, motor impairment, fatigue, numbness, vision problems and cognitive loss. However, the etiology of MS is still unknown, but epidemiological studies suggested that multiple sclerosis may occur in a genetically susceptible population who has been exposed to some environmental triggering factors, such as viral infection [16, 107]. Such factors, therefore, associated with a genetically susceptibility, drives the immune response towards myelin self-peptides which devastates the myelin sheathes, causing the neurodegenerative profile of MS. To this extent, the inflammatory-mediated damage is thought to be caused by the release of reactive oxygen and nitrogen species by immune cells, as well as that of cytokines, prostaglandins and proteases, which directly mediate cell damage [56].

The autoimmune characteristic of MS has been reproduced in animal models such as experimental autoimmune encephalomyelitis (EAE) and Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). These models are employed in pharmacological research and provide suitable evidence for new treatment strategies. Since there is no cure for MS, any treatment is only a palliative resource. Due to its intriguing anti-inflammatory effects, cannabinoid compounds have been tested in animal models of MS as a supportive treatment for symptoms like spasticity and tremor, which are common in patients with MS (see Table 22). Lyman et al. [108] demonstrated that animals pretreated with Δ9-THC displayed a delay in the onset of the symptoms and a reduction in severity when EAE was subsequently induced. In studies using synthetic cannabinoids, dexanabinol (HU-211) was capable to reduce inflammation and EAE score, probably by suppression of TNF-α production in the brain and peripheral blood [109]. Administration of WIN55,212-2 ameliorated the progression of clinical symptoms in mice with TMEV-IDD [105], a mouse model of chronic-progressive MS and EAE [77]. Similar results were obtained by Arévalo-Martín et al. [110] who found that systemic treatment with WIN55,212-2, ACEA, and JWH-015 over a period of 10 days to mice with established TMEV-IDD improved their motor function by modulating microglia and lymphocyte infiltration into the spinal cord. Interestingly, the selective CB1 antagonist SR141716A increased EAE clinical score probably by releasing pro-inflammatory cytokines such as IFN-γ, IL-17, IL-6, IL-1β and TNF-α in mice brain and spinal cord. However, such treatment was able to simultaneously increase CB2 receptors expression in brain, spinal cord and spleen of mice [111]. It is worthy of mention that combined cannabinoid medicine constituted by the two plant-derived cannabinoids THC and CBD have been formulated under an oromucosal mouth spray (Sativex®) to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms associated with MS [112].

Table 2.
Pre-clinical Studies using Cannabinoids on Experimental Autoimmune Encephalomyelitis and Theiler’s Murine Encephalomyelitis Virus-induced Demyelinating Disease

As commented above, expansion of Treg cells has been emerged as a promising candidate therapy to treat (or even prevent) autoimmune diseases such as MS (Rezende et al., manuscript in preparation [113]). It is already known that cannabinoids are able to increase Treg population, which effectively contributes to their immune-modulatory actions by dampening the uncontrolled encephalitogenic T cells proliferation and activation [48, 49, 114]. Moreover, expanding Treg cells derived from the patient itself would provide an important tool to treat/prevent MS with no side effects.


Due to its peculiar chemistry, cannabinoids have imposed a challenge to researchers. To date, it is still impossible to prove or rule out all benefits of cannabis described empirically by ancient herbal practitioners. For now, science aims to understand how cannabinoid compounds are associated with neuroinflammation and how cannabis-based medicine can help millions of patients worldwide. The development of safe, effective cannabis-based medicines must overcome the risk of adverse effects.


The authors thank David H. Rodrigues for manuscript review. This work was supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil.


Declared none.


1. Mechoulam R E. Cannabinoids as Therapeutics. Basel: Birkhäuser; 2005. p. 272.
2. Mechoulam R, Gaoni Y. A Total Synthesis of Dl-Delta-1-Tetrahydrocannabinol, the Active Constituent of Hashish. J. Am. Chem. Soc. 1965;87:3273–5. [PubMed]
3. Devane W A, Dysarz F A, 3rd, Johnson M R, Melvin L S, Howlett A C. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol. 1988;34(5):605–13. [PubMed]
4. Matsuda L A, Lolait S J, Brownstein M J, Young A C, Bonner T I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346(6284):561–4. [PubMed]
5. Herkenham M, Lynn A B, Johnson M R, Melvin L S, de Costa B R, Rice K C. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J. Neurosci. 1991;11(2):563–83. [PubMed]
6. Moldrich G, Wenger T. Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides. 2000;21(11):1735–42. [PubMed]
7. Martin W J, Patrick S L, Coffin P O, Tsou K, Walker J M. An examination of the central sites of action of cannabinoid-induced antinociception in the rat. Life Sci. 1995;56(23-24):2103–9. [PubMed]
8. Martin W J, Tsou K, Walker J M. Cannabinoid receptor-mediated inhibition of the rat tail-flick reflex after microinjection into the rostral ventromedial medulla. Neurosci. Lett. 1998;242(1):33–6. [PubMed]
9. Martin W J, Coffin P O, Attias E, Balinsky M, Tsou K, Walker J M. Anatomical basis for cannabinoid-induced antinociception as revealed by intracerebral microinjections. Brain Res. 1999;822(1-2):237–42. [PubMed]
10. Wang T, Collet J P, Shapiro S, Ware M A. Adverse effects of medical cannabinoids: a systematic review. CMAJ. 2008;178(13):1669–78. [PMC free article] [PubMed]
11. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003;362(9395):1517–26. [PubMed]
12. Smith P F. Symptomatic treatment of multiple sclerosis using cannabinoids: recent advances. Expert Rev. Neurother. 2007;7(9):1157–63. [PubMed]
13. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur. J. Biochem. 1995;232(1):54–61. [PubMed]
14. Pertwee R G, Howlett A C, Abood M E, Alexander S P, Di Marzo V, Elphick M R, Greasley P J, Hansen H S, Kunos G, Mackie K, Mechoulam R, Ross R A. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol Rev. 2010;62(4):588–631. [PubMed]
15. Howlett A C, Barth F, Bonner T I, Cabral G, Casellas P, Devane W A, Felder C C, Herkenham M, Mackie K, Martin B R, Mechoulam R, Pertwee R G. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev. 2002;54(2):161–202. [PubMed]
16. Arevalo-Martin A, Garcia-Ovejero D, Gomez O, Rubio-Araiz A, Navarro-Galve B, Guaza C, Molina-Holgado E, Molina-Holgado F. CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies. Br. J. Pharmacol. 2008;153(2):216–25. [PMC free article] [PubMed]
17. Benito C, Tolon R M, Pazos M R, Nunez E, Castillo A I, Romero J. Cannabinoid CB2 receptors in human brain inflammation. Br. J. Pharmacol. 2008;153(2):277–85. [PMC free article] [PubMed]
18. Munro S, Thomas K L, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61–5. [PubMed]
19. Cabral G A, Marciano-Cabral F. Cannabinoid receptors in microglia of the central nervous system: immune functional relevance. J. Leukoc. Biol. 2005;78(6):1192–7. [PubMed]
20. Patel K D, Davison J S, Pittman Q J, Sharkey K A. Cannabinoid CB(2) receptors in health and disease. Curr. Med. Chem. 2010;17(14):1393–410. [PubMed]
21. Van Sickle M D, Duncan M, Kingsley P J, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison J S, Marnett L J, Di Marzo V, Pittman Q J, Patel K D, Sharkey K A. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005;310(5746):329–32. [PubMed]
22. Carlisle S J, Marciano-Cabral F, Staab A, Ludwick C, Cabral G A. Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Int. Immunopharmacol. 2002;2(1):69–82. [PubMed]
23. Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N. Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J. Neurosci. 2003;23(4):1398–405. [PubMed]
24. Stella N. Cannabinoid signaling in glial cells. Glia. 2004;48(4):267–77. [PubMed]
25. Maresz K, Pryce G, Ponomarev E D, Marsicano G, Croxford J L, Shriver L P, Ledent C, Cheng X, Carrier E J, Mann M K, Giovannoni G, Pertwee R G, Yamamura T, Buckley N E, Hillard C J, Lutz B, Baker D, Dittel B N. Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat. Med. 2007;13(4):492–7. [PubMed]
26. Cabral G A, Raborn E S, Griffin L, Dennis J, Marciano-Cabral F. CB2 receptors in the brain: role in central immune function. Br. J. Pharmacol. 2008;153(2):240–51. [PMC free article] [PubMed]
27. Pietr M, Kozela E, Levy R, Rimmerman N, Lin Y H, Stella N, Vogel Z, Juknat A. Differential changes in GPR55 during microglial cell activation. FEBS Lett. 2009;583(12):2071–6. [PubMed]
28. Benito C, Nunez E, Tolon R M, Carrier E J, Rabano A, Hillard C J, Romero J. Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. J. Neurosci. 2003;23(35):11136–41. [PubMed]
29. Zhang J, Hoffert C, Vu H K, Groblewski T, Ahmad S, O'Donnell D. Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur. J. Neurosci. 2003;17(12):2750–4. [PubMed]
30. Yiangou Y, Facer P, Durrenberger P, Chessell I P, Naylor A, Bountra C, Banati R R, Anand P. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol. 2006;6:12. [PMC free article] [PubMed]
31. Walker J M, Huang S M. Cannabinoid analgesia. Pharmacol. Ther. 2002;95(2):127–35. [PubMed]
32. Devane W A, Hanus L, Breuer A, Pertwee R G, Stevenson L A, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946–9. [PubMed]
33. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski N E, Schatz A R, Gopher A, Almog S, Martin B R, Compton D R, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 1995;50(1):83–90. [PubMed]
34. Kreitzer A C, Regehr W G. Retrograde signaling by endocannabinoids. Curr. Opin. Neurobiol. 2002;12(3):324–30. [PubMed]
35. Sugiura T, Kishimoto S, Oka S, Gokoh M. Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog. Lipid Res. 2006;45(5):405–46. [PubMed]
36. Rodriguez de Fonseca F, Del Arco I, Bermudez-Silva F J, Bilbao A, Cippitelli A, Navarro M. The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol. 2005;40(1):2–14. [PubMed]
37. Ahn K, Johnson D S, Cravatt B F. Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders. Expert Opin. Drug Discov. 2009;4(7):763–784. [PMC free article] [PubMed]
38. Pertwee R G. Pharmacological actions of cannabinoids. Handb Exp. Pharmacol. 2005. pp. 1–51. [PubMed]
39. Felder C C, Joyce K E, Briley E M, Mansouri J, Mackie K, Blond O, Lai Y, Ma A L, Mitchell R L. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol. Pharmacol. 1995;48(3):443–50. [PubMed]
40. Reggio P H. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Curr. Med. Chem. 2010;17(14):1468–86. [PubMed]
41. Ashton J C, Wright J L, McPartland J M, Tyndall J D. Cannabinoid CB1 and CB2 receptor ligand specificity and the development of CB2-selective agonists. Curr. Med. Chem. 2008;15(14):1428–43. [PubMed]
42. Begg M, Pacher P, Batkai S, Osei-Hyiaman D, Offertaler L, Mo F M, Liu J, Kunos G. Evidence for novel cannabinoid receptors. Pharmacol. Ther. 2005;106(2):133–45. [PubMed]
43. Dalton G D, Bass C E, Van Horn C G, Howlett A C. Signal transduction via cannabinoid receptors. CNS Neurol. Disord. Drug Targets. 2009;8(6):422–31. [PubMed]
44. Demuth D G, Molleman A. Cannabinoid signalling. Life Sci. 2006;78(6):549–63. [PubMed]
45. Howlett A C. Cannabinoid receptor signaling. Handb. Exp. Pharmacol. 2005. pp. 53–79. [PubMed]
46. Sharir H, Abood M E. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol. Ther. 2010;126(3):301–13. [PMC free article] [PubMed]
47. Rayman N, Lam K H, Laman J D, Simons P J, Lowenberg B, Sonneveld P, Delwel R. Distinct expression profiles of the peripheral cannabinoid receptor in lymphoid tissues depending on receptor activation status. J. Immunol. 2004;172(4):2111–7. [PubMed]
48. Klein T W, Newton C, Larsen K, Lu L, Perkins I, Nong L, Friedman H. The cannabinoid system and immune modulation. J. Leukoc. Biol. 2003;74(4):486–96. [PubMed]
49. Klein T W, Newton C, Friedman H. Cannabinoid receptors and immunity. Immunol. Today. 1998;19(8):373–81. [PubMed]
50. Giovannoni G. Cannabinoids and B cells: emerging targets for treating progressive multiple sclerosis. Mult. Scler. 2011;17(3):259–61. [PubMed]
51. Berdyshev E V, Schmid P C, Krebsbach R J, Schmid H H. Activation of PAF receptors results in enhanced synthesis of 2-arachidonoylglycerol (2-AG) in immune cells. FASEB J. 2001;15(12):2171–8. [PubMed]
52. Zhao Y, Liu Y, Zhang W, Xue J, Wu Y Z, Xu W, Liang X, Chen T, Kishimoto C, Yuan Z. WIN55212-2 ameliorates atherosclerosis associated with suppression of pro-inflammatory responses in ApoE-knockout mice. Eur. J. Pharmacol. 2010;649(1-3):285–92. [PubMed]
53. Klein T W. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol. 2005;5(5):400–11. [PubMed]
54. Howlett A C. The cannabinoid receptors. Prostaglandins Other Lipid Mediat. 2002;68-69:619–31. [PubMed]
55. Klegeris A, Bissonnette C J, McGeer P L. Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br. J. Pharmacol. 2003;139(4):775–86. [PMC free article] [PubMed]
56. Correa F, Mestre L, Molina-Holgado E, Arevalo-Martin A, Docagne F, Romero E, Molina-Holgado F, Borrell J, Guaza C. The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation. Mini Rev. Med. Chem. 2005;5(7):671–5. [PubMed]
57. Correa F, Docagne F, Mestre L, Clemente D, Hernangomez M, Loria F, Guaza C. A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells. Biochem. Pharmacol. 2009;77(1):86–100. [PubMed]
58. Jean-Gilles L, Gran B, Constantinescu C S. Interaction between cytokines, cannabinoids and the nervous system. Immunobiology. 2010;215(8):606–10. [PubMed]
59. Mestre L, Inigo P M, Mecha M, Correa F G, Hernangomez-Herrero M, Loria F, Docagne F, Borrell J, Guaza C. Anandamide inhibits Theiler's virus induced VCAM-1 in brain endothelial cells and reduces leukocyte transmigration in a model of blood brain barrier by activation of CB(1) receptors. J. Neuroinflamm. 2011;8:102. [PMC free article] [PubMed]
60. Engelhardt B, Ransohoff R M. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 2005;26(9):485–95. [PubMed]
61. Greenwood J, Heasman S J, Alvarez J I, Prat A, Lyck R, Engelhardt B. Review: leucocyte-endothelial cell crosstalk at the blood-brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol. Appl. Neurobiol. 2011;37(1):24–39. [PubMed]
62. Zoppi S, Perez Nievas B G, Madrigal J L, Manzanares J, Leza J C, Garcia-Bueno B. Regulatory role of cannabinoid receptor 1 in stress-induced excitotoxicity and neuroinflammation. Neuropsychopharmacology. 2011;36(4):805–18. [PMC free article] [PubMed]
63. Downer E J. Cannabinoids and innate immunity: taking a toll on neuroinflammation. Sci. World J. 2011;11:855–65. [PubMed]
64. Prinz M, Garbe F, Schmidt H, Mildner A, Gutcher I, Wolter K, Piesche M, Schroers R, Weiss E, Kirschning C J, Rochford C D, Bruck W, Becher B. Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J. Clin. Invest. 2006;116(2):456–64. [PMC free article] [PubMed]
65. Aravalli R N, Peterson P K, Lokensgard J R. Toll-like receptors in defense and damage of the central nervous system. J. Neuroimmune Pharmacol. 2007;2(4):297–312. [PubMed]
66. Jack C S, Arbour N, Manusow J, Montgrain V, Blain M, McCrea E, Shapiro A, Antel J P. TLR signaling tailors innate immune responses in human microglia and astrocytes. J. Immunol. 2005;175(7):4320–30. [PubMed]
67. Mishra B B, Gundra U M, Teale J M. Expression and distribution of Toll-like receptors 11-13 in the brain during murine neurocysticercosis. J. Neuroinflamm. 2008;5:53. [PMC free article] [PubMed]
68. Mishra B B, Mishra P K, Teale J M. Expression and distribution of Toll-like receptors in the brain during murine neurocysticercosis. J. Neuroimmunol. 2006;181(1-2):46–56. [PMC free article] [PubMed]
69. Tang S C, Arumugam T V, Xu X, Cheng A, Mughal M R, Jo D G, Lathia J D, Siler D A, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson M P. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc. Natl. Acad. Sci. U. S. A. 2007;104(34):13798–803. [PubMed]
70. Bsibsi M, Ravid R, Gveric D, van Noort J M. Broad expression of Toll-like receptors in the human central nervous system. J. Neuropathol. Exp. Neurol. 2002;61(11):1013–21. [PubMed]
71. Takeda K, Akira S. TLR signaling pathways. Semin. Immunol. 2004;16(1):3–9. [PubMed]
72. Facchinetti F, Del Giudice E, Furegato S, Passarotto M, Leon A. Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide. Glia. 2003;41(2):161–8. [PubMed]
73. Waksman Y, Olson J M, Carlisle S J, Cabral G A. The central cannabinoid receptor (CB1) mediates inhibition of nitric oxide production by rat microglial cells. J. Pharmacol. Exp. Ther. 1999;288(3):1357–66. [PubMed]
74. Froger N, Orellana J A, Cohen-Salmon M, Ezan P, Amigou E, Saez J C, Giaume C. Cannabinoids prevent the opposite regulation of astroglial connexin43 hemichannels and gap junction channels induced by pro-inflammatory treatments. J. Neurochem. 2009;111(6):1383–97. [PubMed]
75. Cabral G A, Harmon K N, Carlisle S J. Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation. Adv. Exp. Med. Biol. 2001;493:207–14. [PubMed]
76. Molina-Holgado F, Molina-Holgado E, Guaza C, Rothwell N J. Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures. J. Neurosci. Res. 2002;67(6):829–36. [PubMed]
77. Downer E J, Clifford E, Gran B, Nel H J, Fallon P G, Moynagh P N. Identification of the synthetic cannabinoid R(+)WIN55,212-2 as a novel regulator of IFN regulatory factor 3 activation and IFN-beta expression: relevance to therapeutic effects in models of multiple sclerosis. J. Biol. Chem. 2011;286(12):10316–28. [PMC free article] [PubMed]
78. Booz G W. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic. Biol. Med. 2011;51(5):1054–61. [PMC free article] [PubMed]
79. Mukhopadhyay P, Rajesh M, Horvath B, Batkai S, Park O, Tanchian G, Gao R Y, Patel V, Wink D A, Liaudet L, Hasko G, Mechoulam R, Pacher P. Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic. Biol. Med. 2011;50(10):1368–81. [PMC free article] [PubMed]
80. Cassol-Jr O J, Comim C M, Silva B R, Hermani F V, Constantino L S, Felisberto F, Petronilho F, Hallak J E, De Martinis B S, Zuardi A W, Crippa J A, Quevedo J, Dal-Pizzol F. Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture. Brain Res. 2010;1348:128–38. [PubMed]
81. Ruiz-Valdepenas L, Martinez-Orgado J A, Benito C, Millan A, Tolon R M, Romero J. Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study. J. Neuroinflamm. 2011;8(1):5. [PMC free article] [PubMed]
82. Eubanks L M, Rogers C J, Beuscher A E t, Koob G F, Olson A J, Dickerson T J, Janda K D. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol. Pharm. 2006;3(6):773–7. [PMC free article] [PubMed]
83. Esposito G, Scuderi C, Savani C, Steardo L, Jr, De Filippis D, Cottone P, Iuvone T, Cuomo V, Steardo L. Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br. J. Pharmacol. 2007;151(8):1272–9. [PMC free article] [PubMed]
84. Ramirez B G, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos M L. Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J. Neurosci. 2005;25(8):1904–13. [PubMed]
85. Mazzola C, Micale V, Drago F. Amnesia induced by beta-amyloid fragments is counteracted by cannabinoid CB1 receptor blockade. Eur. J. Pharmacol. 2003;477(3):219–25. [PubMed]
86. Chen B, Bromley-Brits K, He G, Cai F, Zhang X, Song W. Effect of synthetic cannabinoid HU210 on memory deficits and neuropathology in Alzheimer's disease mouse model. Curr. Alzheimer Res. 2010;7(3):255–61. [PubMed]
87. Blazquez C, Chiarlone A, Sagredo O, Aguado T, Pazos M R, Resel E, Palazuelos J, Julien B, Salazar M, Borner C, Benito C, Carrasco C, Diez-Zaera M, Paoletti P, Diaz-Hernandez M, Ruiz C, Sendtner M, Lucas J J, de Yebenes J G, Marsicano G, Monory K, Lutz B, Romero J, Alberch J, Gines S, Kraus J, Fernandez-Ruiz J, Galve-Roperh I, Guzman M. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease. Brain. 2011;134(Pt 1):119–36. [PubMed]
88. Dowie M J, Howard M L, Nicholson L F, Faull R L, Hannan A J, Glass M. Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington's disease transgenic mice. Neuroscience. 2010;170(1):324–36. [PubMed]
89. Lastres-Becker I, Bizat N, Boyer F, Hantraye P, Brouillet E, Fernandez-Ruiz J. Effects of cannabinoids in the rat model of Huntington's disease generated by an intrastriatal injection of malonate. Neuroreport. 2003;14(6):813–6. [PubMed]
90. Sagredo O, Gonzalez S, Aroyo I, Pazos M R, Benito C, Lastres-Becker I, Romero J P, Tolon R M, Mechoulam R, Brouillet E, Romero J, Fernandez-Ruiz J. Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington's disease. Glia. 2009;57(11):1154–67. [PMC free article] [PubMed]
91. Pintor A, Tebano M T, Martire A, Grieco R, Galluzzo M, Scattoni M L, Pezzola A, Coccurello R, Felici F, Cuomo V, Piomelli D, Calamandrei G, Popoli P. The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology. 2006;51(5):1004–12. [PubMed]
92. Consroe P, Laguna J, Allender J, Snider S, Stern L, Sandyk R, Kennedy K, Schram K. Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacol. Biochem. Behav. 1991;40(3):701–8. [PubMed]
93. Price D A, Martinez A A, Seillier A, Koek W, Acosta Y, Fernandez E, Strong R, Lutz B, Marsicano G, Roberts J L, Giuffrida A. WIN55,212-2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Eur. J. Neurosci. 2009;29(11):2177–86. [PMC free article] [PubMed]
94. Tagliaferro P, Javier R A, Onaivi E S, Evrard S G, Lujilde J, Brusco A. Neuronal cytoskeleton and synaptic densities are altered after a chronic treatment with the cannabinoid receptor agonist WIN 55,212-2. Brain Res. 2006;1085(1):163–76. [PubMed]
95. Gonzalez S, Scorticati C, Garcia-Arencibia M, de Miguel R, Ramos J A, Fernandez-Ruiz J. Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson's disease. Brain Res. 2006;1073-1074:209–19. [PubMed]
96. Lastres-Becker I, Molina-Holgado F, Ramos J A, Mechoulam R, Fernandez-Ruiz J. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. Neurobiol. Dis. 2005;19(1-2):96–107. [PubMed]
97. Haga S, Akai K, Ishii T. Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol. 1989;77(6):569–75. [PubMed]
98. Gowran A, Noonan J, Campbell V A. The Multiplicity of Action of Cannabinoids: Implications for Treating Neuro-degeneration. CNS Neurosci. Ther. 2011;17:637–644. [PubMed]
99. Kofalvi A, Rodrigues R J, Ledent C, Mackie K, Vizi E S, Cunha R A, Sperlagh B. Involvement of cannabinoid receptors in the regulation of neurotransmitter release in the rodent striatum: a combined immunochemical and pharmacological analysis. J. Neurosci. 2005;25(11):2874–84. [PubMed]
100. Pisani A, Fezza F, Galati S, Battista N, Napolitano S, Finazzi-Agro A, Bernardi G, Brusa L, Pierantozzi M, Stanzione P, Maccarrone M. High endogenous cannabinoid levels in the cerebrospinal fluid of untreated Parkinson's disease patients. Ann. Neurol. 2005;57(5):777–9. [PubMed]
101. Chen C M. Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington's disease. Chang Gung Med. J. 2011;34(2):135–52. [PubMed]
102. Ross C A, Tabrizi S J. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 2011;10(1):83–98. [PubMed]
103. Lastres-Becker I, Berrendero F, Lucas J J, Martin-Aparicio E, Yamamoto A, Ramos J A, Fernandez-Ruiz J J. Loss of mRNA levels, binding and activation of GTP-binding proteins for cannabinoid CB1 receptors in the basal ganglia of a transgenic model of Huntington's disease. Brain Res. 2002;929(2):236–42. [PubMed]
104. Lastres-Becker I, Fezza F, Cebeira M, Bisogno T, Ramos J A, Milone A, Fernandez-Ruiz J, Di Marzo V. Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington's disease. Neuroreport. 2001;12(10):2125–9. [PubMed]
105. Croxford J L, Miller S D. Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212. J. Clin. Invest. 2003;111(8):1231–40. [PMC free article] [PubMed]
106. Hippen K L, Merkel S C, Schirm D K, Sieben C M, Sumstad D, Kadidlo D M, McKenna D H, Bromberg J S, Levine B L, Riley J L, June C H, Scheinberg P, Douek D C, Miller J S, Wagner J E, Blazar B R. Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity. Sci. Transl. Med. 2011;3(83):83ra41. [PMC free article] [PubMed]
107. Antony J M, Deslauriers A M, Bhat R K, Ellestad K K, Power C. Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants? Biochim. Biophys. Acta. 2011;1812(2):162–76. [PubMed]
108. Lyman W D, Sonett J R, Brosnan C F, Elkin R, Bornstein M B. Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J. Neuroimmunol. 189;23(1):73–81. [PubMed]
109. Achiron A, Miron S, Lavie V, Margalit R, Biegon A. Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis: implications for the treatment of acute relapses of multiple sclerosis. J. Neuroimmunol. 2000;102(1):26–31. [PubMed]
110. Arevalo-Martin A, Vela J M, Molina-Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J. Neurosci. 2003;23(7):2511–6. [PubMed]
111. Lou Z Y, Zhao C B, Xiao B G. Immunoregulation of experimental autoimmune encephalomyelitis by the selective CB1 receptor antagonist. J. Neurosci. Res. 2012;90(1):84–95. [PubMed]
112. Kmietowicz Z. Cannabis based drug is licensed for spasticity in patients with MS. BMJ . 2010;340:c3363. [PubMed]
113. R113 Rezende RM, Oliveira RP, Rabelo SM, Alves AC, Gomes-Santos AC, Guimarães FL, Freitas MA, Amaral SS, Cunha AP, Weiner HL, Miyoshic A, Faria AMC. Oral administration of Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+Foxp3+ and CD4+LAP+ regulatory T cells. Manuscript in preparation. [PMC free article] [PubMed]
114. Hegde V L, Hegde S, Cravatt B F, Hofseth L J, Nagarkatti M, Nagarkatti P S. Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells. Mol. Pharmacol. 2008;74(1):20–33. [PMC free article] [PubMed]

Articles from Current Neuropharmacology are provided here courtesy of Bentham Science Publishers