Cannabis may help stroke recovery

“CANNABIS may help to reduce brain damage after a stroke, new research suggests.

Chemical compounds found in the plant could help shrink the area of the brain affected by stroke, the study says.

Cannabinoids in the plant, as well as those that can be made artificially and those found naturally in the body, can also help improve brain function after a stroke attack, the authors said.

The study, which is to be presented to the annual UK Stroke Forum, examined previous studies conducted on the effect of the compound.

The authors, from the University of Nottingham, examined 94 studies evaluating the effects of cannabinoids on 1022 male rats, mice or monkeys.

They say the chemical “shows promise as a neuroprotective treatment for stroke”.

“This meta-analysis of pre-clinical stroke studies provides valuable information on the existing, and importantly, missing data on the use of cannabinoids as a potential treatment for stroke patients,” said lead author Dr Tim England, honorary consultant stroke physician at the University of Nottingham and Royal Derby Hospital.

Dr Dale Webb, director of research and information at the Stroke Association, added: “Stroke is the leading cause of adult disability in the UK, with more than half of all stroke survivors left dependent on others for everyday activities. With more people in the UK surviving a stroke, it’s never been more important to find new treatments to help more stroke patients make better recoveries.

“This new research is an example of the many new developments in the field of stroke which are being presented at this year’s UK Stroke Forum.

“The findings have identified the potential for cannabinoids to reduce brain damage caused by stroke.”

http://www.news.com.au/world/breaking-news/cannabis-may-help-stroke-recovery/story-e6frfkui-1226774100340

Chemicals in Marijuana May Help Stroke Victims

NewsBriefs

“Scientists at the National Institute of Mental Health (NIMH) said a chemical in marijuana may protect the brain from damage inflicted by a stroke.

Their study was reported in the Proceedings of the National Academy of Sciences (Aidan Hampson, et al., “Cannabidiol and Delta-9-tetrahydrocannabinol Are Neuroprotective Antioxidants,” Proceedings of the National Academy of Sciences, July 7, 1998, Vol. 95, Issue 14, p. 8268; “Pot Chemicals Might Inhibit Breast Tumors, Stroke Damage,” Dallas Morning News, July 13, 1998; Vanessa Thorpe, “Chemicals Help Brain Damage After Stroke,” The Independent (UK), July 19, 1998).

NIMH scientists researched the effects of two cannabinoids, cannabidiol and THC, on the brains of rats. THC is the ingredient in marijuana that causes a psychoactive effect. However, cannabidiol is “a better candidate,” in part, because it does not cause a “high” in the patient, said Aidan Hampson, a neuropharmacologist at NIMH who led the study.

The cannabinoids block a neurochemical, known as glutamate, that leads to the formation of toxic oxidizing molecules that kill brain cells. Glutamate is produced in the brain if the oxygen supply is cut off, for example, as the result of blood clot leading to a stroke.

Researchers found that cannabidiol is a more effective antioxidant than vitamins A and E, which already are known to block the damaging effects of glutamate.”

http://www.ndsn.org/julaug98/medmj1.html

CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies

Figure 2

“Amongst the various demyelinating diseases that affect the central nervous system, those induced by an inflammatory response stand out because of their epidemiological relevance. The best known inflammatory-induced demyelinating disease is multiple sclerosis, but the immune response is a common pathogenic mechanism in many other less common pathologies (e.g., acute disseminated encephalomyelitis and acute necrotizing haemorrhagic encephalomyelitis).

In all such cases, modulation of the immune response seems to be a logical therapeutic approach.

Cannabinoids are well known immunomodulatory molecules that act through CB1 and CB2 receptors. While activation of CB1 receptors has a psychotropic effect, activation of CB2 receptors alone does not. Therefore, to bypass the ethical problems that could result from the treatment of inflammation with psychotropic molecules, considerable effort is being made to study the potential therapeutic value of activating CB2 receptors.

In this review we examine the current knowledge and understanding of the utility of cannabinoids as therapeutic molecules for inflammatory-mediated demyelinating pathologies. Moreover, we discuss how CB2 receptor activation is related to the modulation of immunopathogenic states.

The activation of CB2receptors results in the modulation of the inflammatory response, restraining one of the agents responsible for the progress of demyelination and neuronal death, the ultimate causes of the symptoms in pathologies such as MS and EAE.

The modulation of inflammatory molecules through CB2 receptors could also enhance remyelination, stimulating the survival of oligodendrocyte precursors and neural stem/precursor cells, and their development into mature oligodendrocytes.

…this raises the possibility that CB2 agonists could have the potential to promote brain repair.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219542/#!po=48.0769

Multiple sclerosis may disrupt endocannabinoid brain protection mechanism

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“Since the discovery of the endocannabinoids [eCB; anandamide and 2-arachidonoylglycerol (2-AG), various pathological conditions were shown to increase the eCB tone and to inhibit molecular mechanisms that are involved in the production, release, and diffusion of harmful mediators such as proinflammatory cytokines or excess glutamate.

In this issue of PNAS, Witting et al.  demonstrate that, unexpectedly and contrary to the effects of other brain diseases, cell damage induced by experimental autoimmune encephalomyelitis (EAE), an immune-mediated disease widely used as a laboratory model of multiple sclerosis (MS), does not lead to enhancement of eCB levels, although the cannabinoid receptors remain functional.

Nearly two decades ago, Lyman et al.  reported that Δ9-THC, the psychoactive component of marijuana, suppresses the symptoms of EAE. A few years later, Wirguin et al. reported the same effect by Δ8-THC, a more stable and less psychotropic analogue of Δ9-THC.

Thus, THC was shown to inhibit both clinical and histological signs of EAE even before the endocannabinoids were described.

THC was also shown to control spasticity and tremor in chronic relapsing EAE, a further autoimmune model of MS , and to inhibit glutamate release via activation of the CB1-cannabinoid receptor in EAE. Moreover, mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration after immune attack in EAE.

Thus, the brain loses some of its endogenous neuroprotective capacity, but it may still respond to exogenous treatment with 2-AG or other CB1 agonists. Assuming that the biochemical changes taking place in the EAE model of MS are similar to those in MS itself, these results represent a biochemical-based support to the positive outcome noted with cannabinoid therapy in MS.

These data suggest that the high level of IFN-γ in the CNS, noted in mice with EAE, disrupts eCB-mediated neuroprotection, while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458835/

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

“Cannabis has been used to treat disease since ancient times. Δ9 -Tetrahydrocannabinol (Δ9 -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis.

Cannabis and Δ9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ9 -THC limit tolerability.

CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models.

The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors.

CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive.

More recent anecdotal reports of high-ratio CBD:Δ9 -THC medical marijuana have claimed efficacy, but studies were not controlled.

CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy.”

http://www.ncbi.nlm.nih.gov/pubmed/24854329

Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity.

“Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties…

Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity…

Our results indicate that Δ9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.”

http://www.ncbi.nlm.nih.gov/pubmed/24844285

Full-text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028295/

A restricted population of CB1 cannabinoid receptors with neuroprotective activity.

“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…

The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/24843137

The influence of cannabinoids on generic traits of neurodegeneration

“In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure.

Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties.

Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full

Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice.

“Patients suffering from Alzheimer’s disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces…

The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model.

Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.”

http://www.ncbi.nlm.nih.gov/pubmed/24577515

Protective Effects of Cannabidiol Against Hippocampal Cell Death and Cognitive Impairment Induced by Bilateral Common Carotid Artery Occlusion in Mice.

“The present study investigated whether cannabidiol (CBD), a major non-psychoactive constituent of marijuana, protects against hippocampal neurodegeneration and cognitive deficits induced by brain ischemia in adult mice…

These findings suggest a protective effect of CBD on neuronal death induced by ischemia and indicate that CBD might exert beneficial therapeutic effects in brain ischemia. The mechanisms that underlie the neuroprotective effects of CBD in BCCAO mice might involve the inhibition of reactive astrogliosis.”

http://www.ncbi.nlm.nih.gov/pubmed/24532152