Tag Archives: neuroprotection

Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

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“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/

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

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“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…

 We have previously reported that CBD  has a potent and long-lasting neuroprotective effect when administered both pre- and post-ischemia, whereas only pre-ischemic treatment with delta9-THC reduced the infarction size…

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…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036658/

http://www.thctotalhealthcare.com/category/stroke-2/

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury.

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/25206720

Cannabinoids: a novel treatment for glaucoma

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Acta Ophthalmologica

“…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

http://www.thctotalhealthcare.com/category/glaucoma-2/

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease.

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“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.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/

http://www.thctotalhealthcare.com/category/huntingtons/

Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity.

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Brain

“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.”

 http://brain.oxfordjournals.org/content/132/11/3152.long

http://www.thctotalhealthcare.com/category/huntingtons/

Mechanisms of control of neuron survival by the endocannabinoid system.

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“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.

Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.

Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.

Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.

Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/18781978

Cannabinoids and Neuroprotection in Stroke

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“One of the most recently described neural signaling systems is that mediated by endogenous cannabinoids (endocannabinoids). Cannabinoids have recently been shown to attenuate neuronal injury induced by hypoxia and glucose deprivation in cell culture, as well as injury induced in rat brain following both global and focal cerebral ischemia in vivo.

Two endocannabinoids have been characterized in detail: N-arachidonylethanolamide and 2-arachidonylglycerol. Cannabinoid CB1 and CB2receptors have been cloned and an alternatively spliced CB1A isoform has been identified.

The development of metabolically stable, synthetic, enantiomeric cannabinoid receptor agonists and of CB1 and CB2 receptor antagonists has greatly aided the characterization of cannabinoid receptor-mediated processes, although certain aspects of cannabinoid signaling in some systems remain poorly understood.

Indirect evidence suggests that cannabinoids might serve as endogenous regulators of ischemic neuronal injury, but several recent reports provide more direct evidence bearing on such a role.

The author’s own findings provide evidence for CB1 receptor-mediated neuroprotection in vivo, but non-receptor-mediated protection in vitro.”

http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=3&p_RefId=129&p_IsPs=Y

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection

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“Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site.

Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid receptors, the molecular target for marijuana-derived compounds.

Indeed, activation of cannabinoid receptors reduces the production and diffusion of harmful mediators.

Here, we provide evidence that an exception to this pattern is found in experimental autoimmuneencephalomyelitis (EAE), a mouse model of multiple sclerosis…

Our data suggest that the high level of CNS IFN-gamma associated with EAE disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458883/

Targeting the Endocannabinoid System for Neuroprotection: A 19F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.

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“Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection…
The endocannabinoid system has been implicated as a therapeutic target for analgesia, anti-emesis, and neuroprotection… These findings provide a potential new therapeutic modality for neuroprotection through dual inhibition of FAAH and anandamide carrier proteins…”

Figure 1