Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice

Rahimi, A; Faizi, Mehrdad; Talebi, Fatemeh; Noorbakhsh, Farshid; Kahrizi, Farzad; Naderi, Nima

doi:10.1016/j.neuroscience.2015.01.030

Cited by 72 publications

(48 citation statements)

References 66 publications

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“…Recently, we reported that CBD administered systemically diminishes the CNS immune infiltration, microglial activation, axonal damage, and motor disabilities in myelin oligodendrocyte glycoprotein (MOG) 35-55-induced EAE mice (11). These observations were confirmed by several other groups (12)(13)(14) using various models of EAE. However, we would like to state that the group of Maresz et al (5) using a model of homogenized spinal cord-induced EAE did not find CBD to be effective in ameliorating the disease symptoms (see also 15).…”

Section: Endocannabinoids As Well As Cannabinoids Present Inmentioning

confidence: 62%

“…The mixtures (4, 5) and (12,13) were reacted with sodium borohydride in ethanol to give the compounds (6) and (14) in 30% yield and the compounds (7) and (15) in 60% yield. They were purified by silica gel chromatography.…”

Section: Resultsmentioning

confidence: 99%

“…Binding of HU-446 and HU-465 to the cannabinoid CB1 and CB2 receptors The compound HU-446 (6) which was derived from natural (À)-CBD binds very weakly to the cannabinoid receptors CB1 (K i value~1 lM) and CB2 (K i value >10 lM) ( Table 1). By contrast, its stereoisomer HU-465 (14), the derivative of synthetic (+)-CBD, behaves as a high affinity ligand of the CB2 receptor (K i value of 12.1 nM) as well as of the CB1 receptor (K i = 76.7 nM) although its affinity to CB1 is around six times lower than to CB2 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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HU‐446 and HU‐465, Derivatives of the Non‐psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells

et al. 2015

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Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here we have studied the anti-inflammatory effects of newly synthesized derivatives of natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) and of synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465) on activated myelin oligodendrocyte glycoprotein (MOG)35-55-specific mouse encephalitogenic T cells (T(MOG) ) driving EAE/MS-like pathologies. Binding assays followed by molecular modeling revealed that HU-446 has negligible affinity toward the cannabinoid CB1 and CB2 receptors while HU-465 binds to both CB1 and CB2 receptors at the high nanomolar concentrations (Ki = 76.7 ± 5.8 nm and 12.1 ± 2.3 nm, respectively). Both, HU-446 and HU-465, at 5 and 10 μm (but not at 0.1 and 1 μm), inhibited the MOG35-55-induced proliferation of autoreactive T(MOG) cells via CB1/CB2 receptor independent mechanisms. Moreover, both HU-446 and HU-465, at 5 and 10 μm, inhibited the release of IL-17, a key autoimmune cytokine, from MOG35-55-stimulated T(MOG) cells. These results suggest that HU-446 and HU-465 have anti-inflammatory potential in inflammatory and autoimmune diseases.

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Section: Endocannabinoids As Well As Cannabinoids Present Inmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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HU‐446 and HU‐465, Derivatives of the Non‐psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells

et al. 2015

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“…ameliorated spasticity or motor deficits in mice with CREAE or TMEV‐IDD, respectively, (Baker et al, ; Loria et al, ) and reduced the severity of neurobehavioral scores in mice with MOG‐induced EAE (Rahimi et al, ). Furthermore, the expression of inflammatory cytokines was greatly reduced by PEA both in TMEV‐IDD and MOG‐induced EAE mice (Loria et al, ; Rahimi et al, ), and these effects were accompanied by decreased demyelination and axonal damage in the latter model (Rahimi et al, ). These data suggest that exogenous PEA might be helpful to compensate or amplify the endogenous defence mechanism deployed by the cells or tissues to counteract neurodegenerative and neuro‐inflammatory processes.…”

Section: Pea and Neurological Disordersmentioning

confidence: 99%

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations

Petrosino

Marzo

2016

British J Pharmacology

248

292

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“…In animal models of acute, inflammatory and neuropathic pain, cannabinoid receptors appear to be involved in the modulation of pain via regulation of γ ‐aminobutyric acid (GABA) and glutamate, pointing to potential benefits of cannabinoids treatment for patients with MS . Moreover, treatment with CBD reduced the severity of neurobehavioral scores of experimental autoimmune encephalomyelitis and progressive MS in mice, pointing to a neuroprotective effect . Clinical studies have demonstrated that an oromucosal spray of nabiximols (THC and CBD in a ratio of approximately 1:1) reduced MS‐related spasticity .…”

Section: The Role Of Cannabinoids In Neurological Diseasesmentioning

confidence: 99%

The role of cannabinoids and leptin in neurological diseases

Ağar

2015

Acta Neurol Scand

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Cannabinoids exert a neuroprotective influence on some neurological diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis and epilepsy. Synthetic cannabinoid receptor agonists/antagonists or compounds can provide symptom relief or control the progression of neurological diseases. However, the molecular mechanism and the effectiveness of these agents in controlling the progression of most of these diseases remain unclear. Cannabinoids may exert effects via a number of mechanisms and interactions with neurotransmitters, neurotropic factors and neuropeptides. Leptin is a peptide hormone involved in the regulation of food intake and energy balance via its actions on specific hypothalamic nuclei. Leptin receptors are widely expressed throughout the brain, especially in the hippocampus, basal ganglia, cortex and cerebellum. Leptin has also shown neuroprotective properties in a number of neurological disorders, such as Parkinson's and Alzheimer's. Therefore, cannabinoid and leptin hold therapeutic potential for neurological diseases. Further elucidation of the molecular mechanisms underlying the effects on these agents may lead to the development of new therapeutic strategies for the treatment of neurological disorders.

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Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice

Cited by 72 publications

References 66 publications

HU‐446 and HU‐465, Derivatives of the Non‐psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells

HU‐446 and HU‐465, Derivatives of the Non‐psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations

The role of cannabinoids and leptin in neurological diseases

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