“We investigated whether glutamate receptor subunit 2 (GluR2) is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice…
In conclusion, GluR2 up-regulation is involved in neuroprotection of EA pretreatment against GCI through CB1R, suggesting that GluR2 may be a novel target for stroke intervention.”
“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.
In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…
The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.
The effect of THC was in part mediated by the cannabinoid receptor CB1.
These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.
THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…
In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models.
This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.
In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.
The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”
“The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain.
In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function.
The CB1 receptor also confers neuroprotection in various experimental models of striatal damage…
Here, by using an array of pharmacological, genetic and pharmacogenetic approaches, we show that (1) CB1receptor engagement protects striatal cells from excitotoxic death via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin complex 1 pathway, which, in turn, (2) induces brain-derived neurotrophic factor (BDNF) expression through the selective activation of BDNF gene promoter IV, an effect that is mediated by multiple transcription factors.
Collectively, these findings unravel a molecular link between CB1 receptor activation and BDNF expression, and support the relevance of the CB1/BDNF axis in promoting striatal neuron survival.”
“Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparuminfection that might cause permanent neurological deficits.
Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties.
In the present work, we evaluated the effects of CBD in a murine model of CM.
CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6).
Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.”
http://www.ncbi.nlm.nih.gov/pubmed/25595981
“Cannabidiol adjuvant treatment increases survival in the murine model of CM. Cannabidiol adjuvant treatment promotes rescue of behavioral and cognitive function.”
https://www.sciencedirect.com/science/article/pii/S0306452215000196
“Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system.
Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms.
However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease.
… we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability.
Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels.
In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans…
… demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo.
Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.”
http://www.ncbi.nlm.nih.gov/pubmed/25537576
http://www.thctotalhealthcare.com/category/experimental-autoimmune-encephalomyelitis/
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
“Cannabis contains over 60 different terpeno-phenol compounds…
cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV) are known as non-psychoactive components of cannabis.
These compounds have shown anti-inflammatory, immunosuppressive, analgesic, anxiolytic and anti-cancer effects…
Cannabinoids may play a role in neuroprotection in disorders such as stroke, Parkinson’s disease, traumatic brain injury and epilepsy…
It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury…
Accumulating data now suggest that cannabinoid CB1 receptors contribute to neuroprotection… Emerging data now support the evidence of the anti-inflammatory action of CBD…
These results suggest that CBD may prevent post-ischemic injury progressively induced by ischemic stroke….
…anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.
The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.
In the last 10 years, it has been possible to demonstrate that CBD has the following unique therapeutic profile: 1) a cannabinoid receptor-independent mechanism, 2) long-lasting cerebro- protective effect after ischemic stroke, and lack of development of tolerance.
Moreover, CBD has almost no side effects, including psychotropic activity.
Preliminary studies highlight the fact that the multifunctional actions of CBD may lead to benefits in more complex systems within the brain after ischemic stroke.
CBD offers new therapeutic possibilities for treating ischemic stroke…”
“One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death.
Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.
Among them, the endocannabinoid system emerges as a natural system of neuroprotection.
The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant.
The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.”
“…cannabinoids are emerging novel agents for the treatment of glaucoma.
Although increased intraocular pressure (IOP) is a risk factor, associated retinal damage is of prime concern. This study determines the ability of cannabinoids to decrease IOP and confer neuroprotection…
Conclusion: Topically applied cannabinoids are effective agents that reduce IOP and confer neuroprotection and are prime candidates for potential glaucoma treatment.”
http://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2014.T022.x/abstract
“Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders… Cannabinoids may also offer neuroprotection in Huntington’s disease (HD)…
Here, we examined this hypothesis in a rat model ofHuntington’s disease (HD)…
Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed…
…neuroprotection was attained exclusively with antioxidant cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC; or cannabidiol (CBD)…
In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-alpha.
Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD.”
“Cannabinoid-derived drugs are promising agents for the development of novel neuroprotective strategies.
…in Huntington’s disease there is a very early downregulation of CB1 receptors in striatal neurons that, together with the undesirable psychoactive effects triggered by CB1 receptor activation, foster the search for alternative pharmacological treatments.
These findings support a pivotal role for CB2 receptors in attenuating microglial activation and preventing neurodegeneration that may pave the way to new therapeutic strategies for neuroprotection in Huntington’s disease as well as in other neurodegenerative disorders with a significant excitotoxic component.
Overall, the reduction of neuronal CB1 receptors and the upregulation of microglial CB2 receptors support a crucial role for the ECB system in the pathogenesis of Huntington’s disease.
The use of drugs targeting the ECB system via CB1 receptors aimed at restoring neurochemical alterations and palliating symptoms might constitute an interesting strategy for the management of Huntington’s disease and other neurodegenerative disorders with a significant excitotoxicity component.”