Tag Archives: neuroprotective

Cannabis Compound Could Help With Alzheimer’s Disease

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cannabis 

“Neuroscientists suspect the main active ingredient in cannabis, called cannabidiol, could help prevent or reverse early stage brain damage and memory loss from Alzheimer’s disease, according to Australian newspaper the Sydney Morning Herald.

Tim Karl, a senior research fellow with Neuroscience Research Australia, said cannabidiol doesn’t have the same psychoactive effects as marijuana’s main component, THC (meaning it won’t get you high), but it does have anti-inflammatory, antioxidant and possible brain protective effects.

“Back in the day cannabis was used for medical purposes,” he said. “I’m talking 200 years, 100 years back, then at some point people discovered it had other effects and, as quite often happens in our society, people decided it was a bad drug.

But (cannabis isn’t) one compound, it is a mixture of 60 different compounds, and you just have to look at those different compounds because some of them might be good for you.””

Read more: http://www.blisstree.com/2013/02/06/sex-relationships/cannabis-brain/

Update on the Role of Cannabinoid Receptors after Ischemic Stroke

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“The endocannabinoid system is considered as a major modulator of the cerebral blood flow, neuroinflammation, and neuronal survival… Evidence from animal models and in vitro studies suggests a global protective role for cannabinoid receptors agonists in ischemic stroke…Given its potent anti-inflammatory activities on circulating leukocytes, the CB2 activation has been proven to produce protective effects against acute poststroke inflammation. In this paper, we will update evidence on different cannabinoid-triggered avenues to reduce inflammation and neuronal injury in acute ischemic stroke…

Synthetic cannabinoids have been also investigated in animal models showing an improvement of the ischemic injury in the liver, heart, and brain. Furthermore, phytocannabinoids have been also isolated from the Cannabis sativa. Since this plant contains about 80 different cannabinoids, a strong work is still needed to test all these active compounds. This delay in cannabinoid research might be also due to the very low dose of certain cannabinoids in the plant. Thus, since Δ9-tetrahydrocannabidiol (THC) and cannabidiol (CBD) represent up to 40% of the total cannabinoid mass, these compounds have been considered as the most active mediators…

The encouraging therapeutic results of this study are in partial contrast with previous case reports, suggesting a potential relationship between stroke and chronic cannabis abuse in young human beings…

We believe that the “cannabinoid” approach represents an interesting therapeutic strategy still requiring further validations to improve neurologic and inflammatory outcomes in ischemic stroke.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337695/

Modulation of Cannabinoid Receptor Activation as a Neuroprotective Strategy for EAE and Stroke

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“These results provide evidence that alteration of the activation patterns of the various cannabinoid receptors warrant consideration for future therapeutic strategies.

Interest in the medicinal use of Cannabis sativa (marijuana) has a long historical record, extending back thousands of years. In comparison to the extensive history for medicinal applications of marijuana, the existence of an “endocannabinoid system”, with important homeostatic and pathologic functions, has only recently gained appreciation. The endocannabinoid system consists of endogenously produced cannabinoids, their receptors, and the enzymes responsible for their synthesis and degradation…

Although used in ancient Greece, Rome, and China for therapeutic purposes, concern about the use of cannabinoids as a drug of abuse has dampened interest in developing the potential therapeutic benefits of these compounds. However, a better understanding of the biologic effects has led recently to an upsurge in interest for the development of therapeutic drugs through modification of the endocannabinoid system. An additional incentive was provided by the development of synthetic cannabinoid analogs and specific inhibitors of cannabinoid receptors. Several excellent reviews cover the therapeutic potential of cannabinoids….

The present review is focused on the effects of CB2 receptor activation in models of multiple sclerosis (experimental autoimmune encephalomyelitis) and stroke (middle cerebral occlusion/reperfusion).

In summary, selective CB2 receptor agonists and CB1 receptor antagonists have significant potential for neuroprotection in animal models of two devastating diseases that currently lack effective treatment options.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855650/

Modulation of The Balance Between Cannabinoid CB1 and CB2 Receptor Activation During Cerebral Ischemic/Reperfusion Injury

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“A number of investigations have shown that CB2 receptor activation has anti-inflammatory therapeutic potential in various CNS diseases, such as multiple sclerosis, traumatic brain injury and Alzheimer’s disease. Because inflammatory responses have been shown to be important contributors to secondary injury following cerebral ischemia; the CB2 receptor has been investigated as a potential therapeutic target in stroke…

The most striking changes were obtained by combing a CB1 antagonist with a CB2 agonist. This combination elevated the cerebral blood flow during ischemia and reduced infarction by 75%…during cerebral ischemia/reperfusion injury, inhibition of CB1 receptor activation is protective while inhibition of CB2 receptor activation is detrimental.

 The greatest degree of neuroprotection was obtained by combining an inhibitor of CB1 activation with an exogenous CB2 agonist.

In conclusion, the results of this investigation demonstrate dynamic changes in the expression of CB1 and CB2 receptors during cerebral ischemic/reperfusion injury in mice. The effects of stimulation of these receptors on damage ischemia/reperfusion injury differed dramatically. Stimulation of the CB2 receptor was found to be neuroprotective, while inhibition of the CB1 receptor was also protective,too. The combination of a CB2 agonist and a CB1 antagonist provided the greatest degree of protection and indicated a synergistic effect derived from combining these agents. Therefore, changing the balance of stimulation of these receptors by endogenous cannabinoids may provide an important therapeutic strategy during stroke.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577828/

Role of cannabinoids and endocannabinoids in cerebral ischemia

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“The human costs of stroke are very large and growing; it is the third largest cause of death in the United States and survivors are often faced with loss of ability to function independently. There is a large need for therapeutic approaches that act to protect neurons from the injury produced by ischemia and reperfusion… 

 Overall, the available data suggest that inhibition of CB1 receptor activation together with increased CB2 receptor activation produces beneficial effects.

These studies support the hypothesis that activation of the CB1 receptor by highly efficacious, exogenous agonists during the acute phase of ischemia decreases the likelihood of the occurrence of a detrimental event at the time of ischemia and thereby reduces the amount of infarction and neuronal death long-term… A protective role of the CB1 receptor is also supported by studies…

While it is possible that the ECS will be added to the long list of neuroprotective agents that show promise in animals and do not work in humans, there are a few reasons to be optimistic about this class of drugs. First, many of the other agents did not work because they do not cross the blood brain barrier. While the considerable lipophilicity of the cannabinoids poses its own set of problems, these drugs have no problems entering the brain. Second, the ECS is multifactorial and could “cover” multiple biochemical pathways in a single drug. Third, manipulations of the ECS has been shown to be beneficial in several preclinical models. Only time and further research will answer the most important question, are the cannabinoids of therapeutic benefit in humans suffering from stroke?”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581413/

 

Endocannabinoids and cannabinoid receptors in ischaemia–reperfusion injury and preconditioning

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“This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R-induced tissue damage.

In this review, we will discuss the triggers and sources of endocannabinoid production during various forms of I/R injury (myocardial, cerebral, hepatic and retinal ischaemia, and circulatory shock) and preconditioning, as well as the diverse role of these novel mediators and their receptors in these processes. We will also overview the accumulating evidence obtained through the use of various synthetic CB1/CB2 receptor ligands, with particular focus on the novel role of CB2 receptors, suggesting that the modulation of the endocannabinoid system can be therapeutically exploited in various forms of I/R injury.

Cerebral I/R (stroke)

The first evidence for the neuroprotective effect of CBs came from the stroke research field from studies using synthetic non-psychotropic CB Dexanabinol/HU-211, which exerted its beneficial effects through CB1/CB2-independent mechanisms.

Collectively, it appears that both CB1 agonists and antagonists may afford neuroprotective effects against cerebral I/R…

There is considerable interest in the development of selective CB2 receptor agonists, which are devoid of psychoactive properties of CB1 agonists, for various inflammatory disorders. Further studies should also establish the therapeutic window of protection during the reperfusion phase with the currently available CB2 receptor agonists, and new compounds should also be designed with better in vivo bioavailability, to devise clinically relevant treatment strategies against various forms of I/R. Nevertheless, the recently observed beneficial effects of CB2 receptor agonists in hepatic and other forms of I/R, coupled with the absence of psychoactive properties, and antifibrotic effects of CB2 receptor in the liver suggest that this approach may represent a novel promising strategy against various forms of I/R injury and other inflammatory disorders.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219536/

CB1 cannabinoid receptor induction in experimental stroke.

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“Cannabinoids protect cortical neurons from ischemic injury by interacting with CB1 receptors. Because a variety of neuroprotective genes are induced in cerebral ischemia, we examined the effect of experimental stroke, produced by 20 minutes of middle cerebral artery occlusion in rats, on CB1 receptor expression.

Western blotting and immunohistochemistry showed that CB1 expression on neurons was increased in the arterial boundary zone of the cortical mantle, beginning by 2 hours and persisting for 72 hours or more after ischemia.

These findings are consistent with a neuroprotective role for endogenous cannabinoid signaling pathways and with a potential therapeutic role in stroke for drugs that activate CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/10939579

Cannabidiol Relieves Psychosis in Schizophrenia, Why is it Illegal?

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“A molecule in cannabis (CBD) has shown to relieve anxiety and symptoms of psychosis in people diagnosed with schizophrenia, though many patients are denied or discouraged from this medicine with fewer side effects than pharmaceutical products because the DEA has deemed the cannabis plant to be “illegal”. The U.S. government needs to answer “why?” this medicine warrents time in prison when nobody is being harmed.

 Investigators concluded, “Our results provide evidence that the non-cannabimimetic constituent of marijuana, cannabidiol, exerts clinically relevant antipsychotic effects that are associated with marked tolerability and safety, when compared with current medications. … The results … potentially represent a completely new mechanism in the treatment of schizophrenia.”

 “Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer,” Zuardi writes. Let’s look at a few of these in detail, shall we?

1. Antiepileptic action
“In 1973, a Brazilian group reported that CBD was active in … blocking convulsions produced in experimental animals.”

2. Sedative action
“In humans with insomnia, high doses of CBD increased sleep duration compared to placebo.”

3. Anxiolytic action
“CBD induce[s] a clear anxiolytic effect and a pattern of cerebral activity compatible with an anxiolytic activity.”

4. Antipsychcotic action
“[C]linical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients.”

5. Antidystonic action
“CBD … had antidystonic effects in humans when administered along with standard medication to five patients with dystonia, in an open study.”

6. Antioxidative action
“[I]t was demonstrated that CBD can reduce hydroperoxide-induced oxidative damage as well as or better than other antioxidants. CBD was more protective against glutamate neurotoxicity than either ascorbate or a-tocopherol, indicating that this drug is a potent antioxidant.”

7. Neuroprotective action
“A marked reduction in the cell survival was observed following exposure of cultured rat pheochromocytoma PC12 cells to beta-A peptide. Treatment of the cells with CBD prior to beta-A exposure significantly elevated the cell survival.”

8. Antiinflammatory action
“CBD, administered i.p. or orally, has blocked the progression of arthritis.”

9. Cardioprotective action
“CBD induces a substantial cardioprotective effect.”

10. Action on diabetes
“CBD treatment of NOD (non-obese diabetic) mice before the development of the disease reduced its incidence from 86% in the non-treated control mice to 30% in CBD-treated mice. … It was also observed that administration of CBD to 11-14 week old female NOD mice, which were either in a latent diabetes stage or had initial symptoms of diabetes, ameliorated the manifestations of the disease.”

11. Antiemetic action
“The expression of this conditioned retching reaction was completely suppressed by CBD and delta9-THC, but not by ondansetron, [an] antagonist that interferes with acute vomiting.”

12. Anticancer action
“A study of the effect of different cannabinoids on eight tumor cell lines, in vitro, has clearly indicated that, of the five natural compounds tested, CBD was the most potent inhibitor of cancer cell growth.”

In sum, the past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.

What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD (which, under federal law, remains a Schedule I drug defined as having “no currently accepted medical use”)? Perhaps it’s time someone asks John Walters or the DEA?” 

Read more: http://rinf.com/alt-news/latest-news/cannabidiol-relieves-psychosis-in-schizophrenia-why-is-it-illegal/17827/

Pot Compound Reduces Anxiety

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“According to clinical trial data published online in The Journal of Psychopharmacology, the administration of the non-psychoactive component of marijuana [cannabinoid cannabidiol (CBD)] reduces anxiety in subjects with social anxiety disorder (SAD).

The anti-anxiety activity of oral doses of CBD in ten subjects was assessed by investigators at the University of Sao Paulo in Brazil in a double blind, placebo-controlled trial.

Researchers concluded, “CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.”

This study is the first clinical trial to investigate the effects of cannabinoid cannabidiol on human pathological anxiety and its underlying brain mechanisms.

Previous studies in the context of CBD have suggested that the compound possesses anti-inflammatory activity, anti-cancer activity, and neuroprotective effects – among other therapeutic properties.

The study “Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report,” appeared online in The Journal of Psychopharmacology.”

http://www.imarijuana.com/news/pot-compound-reduces-anxiety

Targeting the endocannabinoid system in Alzheimer’s disease.

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“The endocannabinoid system is rapidly emerging as a potential drug target for a variety of immune-mediated central nervous system diseases. There is a growing body of evidence suggesting that endocannabinoid interventions may have particular relevance to Alzheimer’s disease. Here we present a review of endocannabinoid physiology, the evidence that underscores its utility as a potential target for intervention in Alzheimer’s disease, and suggest future pathways of research.

Inflammation and oxidative stress are generally accepted as a critical risk factor for the development of AD, and interventions such as cannabinoids that attenuate these risks without arresting microglial activity and have innate neuroprotective benefits are attractive as potential preventative treatments for AD.

There is a potential for the development of CB1 interventions, whether agonists or antagonists, with applications for a variety of cognitive disorders including neurodegenerative disorders and schizophrenia. The recent discovery of a CB1 receptor Positron Emission Tomography tracer for clinical use may provide the opportunity to evaluate the impact of the regional distribution of CB1 receptors in brain on domain-specific cognitive performance (memory, executive function, praxis) in healthy individuals. Additionally, if AD is a disease of overproduction of eCBs, this may be visualized in case-control CB1receptor binding studies.

The emerging data suggest that the eCB system is a potential target for immune and/or cognitive intervention in AD. A wealth of available chemical compounds capable of intervening in the eCB system at a variety of levels and the success with which these compounds have been used in animal models suggest the potential for human drug development. What is missing is a clear direction for that development based on a concise conceptualization of eCB system function in both health and in neurodegenerative and inflammatory conditions such as AD. Focused experiments are now required to move the field forward.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889705/