Tag Archives: neuroprotective

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/

Chronic cannabinoid receptor stimulation selectively prevents motor impairments in a mouse model of Huntington’s disease.

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“Huntington’s disease (HD) is a devastating neurodegenerative disease…

The endocannabinoid system (ECS) is a relevant candidate to participate in the etiopathology of HD as it is a key modulator of brain function, especially in areas primarily affected by HD…

… improving ECS function may constitute a useful strategy to eliminate or at least delay the appearance of HD symptoms…

…chronic administration was able to prevent the appearance of motor deficits, to increase the number of striatal huntingtin inclusions and to prevent the loss of striatal medium-sized spiny neurons, without affecting the social or cognitive alterations.

These findings suggest that prolonged administration of cannabinoid receptor agonists could be an appropriate strategy for selectively improving motor symptoms and stimulating neuroprotective processes in HD patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25123645

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

Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer’s Disease Transgenic Mice.

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“Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer’s disease (AD).

Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo…

This study is the first to demonstrate CBD’s ability to prevent the development of a social recognition deficit in AD transgenic mice.

Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.”

http://www.ncbi.nlm.nih.gov/pubmed/25024347

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

Researchers study neuroprotective properties in cannabis

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“With more states opting to legalize the sale of medical marijuana, researchers are taking a closer look at the use of cannabis to treat chronic illnesses.

Dr. Manny Alvarez, senior managing health editor of FoxNews.com, recently sat down with the Medicine Hunter, Chris Kilham, to find out how it’s being studied.

Dr. Manny: Now from the medical marijuana perspective, as far as the treatment of chronic illnesses, what is it about cannabis that makes it that special?

Medicine Hunter: Well, it seems that there are primarily two things – there’s the THC, that’s what people associated with getting high. And that appears to have a saliatory effect on the eyes in case of glaucoma. For people who are suffering from chemotherapy and can’t eat, it helps to get their appetite back. And we also know that it is a potent pain reliever – and science on that goes back to the 1890s.

But there’s another agent in cannabis that is getting more attention now, and that is called cannabidiol. And this is something that you can swallow by the bucket-full, and it won’t get you high at all. But it appears to have profound nerve-protective and brain-enhancing properties. And interestingly enough, it also induces an anti-anxiety effect.

So this appears to be a very important agent, perhaps useful in the treatment of neurodegenerative disorders.

DM: Are they extracting that particular chemical off the marijuana?

MH: There seem to be two pathways that people are taking.  You’ve got G.W. pharmaceuticals in Britain that has come out with a whole cannabis fluid spray. You’ve got people also isolating cannabidiol and playing with that in the lab.

I don’t know how this is all going to settle out – I mean, as a whole-plant person, I’m inclined toward the whole extract. But it does appear that this may also have anti-cancer properties, and that’s very intriguing.

DM: Is marijuana addictive?

MH: I would say that people can absolutely become dependent upon it.  But not physiologically addictive.  And, as you know, that’s not just parsing terms – I mean physiological addiction, you go through very grave withdrawal.

But people can become dependent on it just as they can on any substance.

DM: Tell me about this study in the American Journal of Pediatrics talking about pregnant Jamaican women and the use of pot.

MH: Melanie Dreher, who is the dean of nursing at Rush Medical Center inChicago, did a study in Jamaica. It was actually published in the American Journal of Pediatrics in 1994, but now it’s re-circulating because of all the interest in the neuroprotective properties.

Basically, she studied women during their entire pregnancy, and then studied the babies about a year after birth. And what she studied was a group of women who did smoke cannabis during pregnancy and those who didn’t. She expected to see a difference in the babies as far as birth weight and neuro tests, but there was no difference whatsoever. The differences that the researchers did notice, that are unexplained and kind of curious are that the babies of the women who had smoked cannabis — and we’re talking about daily use during their pregnancy — socialized more quickly, made eye contact more quickly and were easier to engage.

We don’t know why this is so, but all the old saws of smoking during pregnancy will result in low birth weight did not show up — at least in the Jamaican study. In U.S. studies where we’ve seen a similar investigation, women have concurrently been abusing alcohol and other drugs as well.

Alvarez said it’s interesting to note that there may be neuroprotective properties present in cannabis and the cannibidiol extract, but that smoking of any kind in pregnant women is discouraged.”

More research is needed when it comes to medical marijuana, he added.”

http://www.foxnews.com/health/2012/03/20/researchers-study-neuroprotective-properties-in-cannabis/

“Study: Cannabis may prevent brain damage” http://www.foxnews.com/health/2013/06/06/study-cannabis-may-prevent-brain-damage/

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury.

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“Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae.

Because of the fact that there is still no specific treatment for perinatal brain lesions due to the complexity of neonatal hypoxic-ischemic pathophysiology, the search of new neuroprotective therapies is of great interest.

In this regard, therapeutic possibilities of the endocannabinoid system have grown lately.

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.

Concerning perinatal asphyxia, the neuroprotective role of this endogenous system is emerging these years.

The present review mainly focused on the current knowledge of the cannabinoids as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

http://www.ncbi.nlm.nih.gov/pubmed/21788999

[The cannabinoid system and its importance in the perinatal period].

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“The cannabinoid system has been recently described, including the endogenous ligands, mainly arachidonic acid derivatives, and their specific receptors. Endocannabinoids are involved in the modulation of synaptic transmission, through which they exert their psychoactive, motor and antinociceptive effects, among others; they also exert extraneural effects, mainly immunomodulation and vasodilation.

Recent data suggest that the cannabinoid system might play an important role in human ontogeny and could participate in the implantation and early development of the embryo, in fetal brain development, and in the beginning of breast feeding after birth.

In addition, the vasodilatory effect of cannabinoids, together with inhibition of the release of excitotoxic amino acids and cytokines, as well as modulation of oxidative stress and the toxic production of nitric oxide, justify the growing evidence pointing to a possible neuroprotective effect of cannabinoids in perinatal asphyxia.”

http://www.ncbi.nlm.nih.gov/pubmed/16266619

Cannabinoids: well-suited candidates for the treatment of perinatal brain injury.

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“Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth… the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited. Hence, there is a dramatic need to develop new effective therapies aimed to prevent acute brain damage and enhance the endogenous mechanisms of long-term brain repair.

The endocannabinoid system is an endogenous neuromodulatory system involved in the control of multiple central and peripheral functions. An early responder to neuronal injury, the endocannabinoid system has been described as an endogenous neuroprotective system that once activated can prevent glutamate excitotoxicity, intracellular calcium accumulation, activation of cell death pathways, microglia activation, neurovascular reactivity and infiltration of circulating leukocytes across the blood-brain barrier.

The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species.

Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration) to neonatal brain injury has been described in independent studies.”

http://www.ncbi.nlm.nih.gov/pubmed/24961520

The Cannabinoid WIN55212-2 Promotes Neural Repair After Neonatal Hypoxia–Ischemia

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Figure 1.

“In the last years, cannabinoids have emerged as promising neuroprotective agents in several animal paradigms of acute and degenerative brain damage. Most neuroprotective effects of cannabinoids result from the activation of cannabinoid Type 1 (CB1R) and Type 2 (CB2R) receptors in neural and immune cells.

Besides, the stimulating effect of cannabinoids on proliferation, survival, and differentiation of neural progenitor cells provides interesting prospects for long-term neural repair after acute brain damage.

The endocannabinoid system has been involved in the modulation of neural stem cells proliferation, survival and differentiation as well as in the generation of new oligodendrocyte progenitors in the postnatal brain. The present work aims to test the effect of the synthetic Type 1 and Type 2 cannabinoid receptor agonist WIN55212-2 on these processes in the context of neonatal rat brain hypoxia–ischemia (HI)…

Our results suggest that the activation of the endocannabinoid system promotes white and gray matter recovery after neonatal HI injury…

In conclusion, we have demonstrated that the synthetic cannabinoid WIN55212-2 enhances SVZ cell proliferation, oligodendrogenesis, white matter remyelination, and neuroblast generation after neonatal HI.

These findings, summed to the previously described neuroprotective properties of cannabinoids after acute brain damage, may possess therapeutic repercussions in the long-term management of neonatal HI encephalopathy, a prevalent and devastating condition for which no pharmacological treatments are yet available.”

http://stroke.ahajournals.org/content/41/12/2956.full