Low doses of marijuana component can protect brain against injury

Low doses of marijuana component can protect brain against injury

 

 

 

 

 

 

“Though marijuana is a well-known recreational drug, extensive scientific research has been conducted on the therapeutic properties of marijuana in the last decade. Medical cannabis is often used by sufferers of chronic ailments, including cancer and post-traumatic stress disorder, to combat pain, insomnia, lack of appetite, and other symptoms.

Now Prof. Yosef Sarne of Tel Aviv University’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine says that the drug has neuroprotective qualities as well. He has found that extremely low doses of THC—the psychoactive component of marijuana—protects the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs. Brain damage can have consequences ranging from mild cognitive deficits to severe neurological damage.

Previous studies focused on injecting high doses of THC within a very short time frame—approximately 30 minutes—before or after injury. Prof. Sarne’s current research, published in the journals Behavioural Brain Research and Experimental Brain Research, demonstrates that even extremely low doses of THC—around 1,000 to 10,000 times less than that in a conventional marijuana cigarette—administered over a wide window of 1 to 7 days before or 1 to 3 days after injury can jumpstart biochemical processes which protect brain cells and preserve cognitive function over time.

This treatment, especially in light of the long time frame for administration and the low dosage, could be applicable to many cases of brain injury and be safer over time…”

More: http://medicalxpress.com/news/2013-05-doses-marijuana-component-brain-injury.html

Marijuana’s THC Can Halt Brain Damage

Cannabis. Image: Hupu2, Wikimedia

“Though marijuana is a well-known recreational drug, extensive scientific research has been conducted on the therapeutic properties of marijuana in the last decade. Medical cannabis is often used by sufferers of chronic ailments, including cancer and post-traumatic stress disorder, to combat pain, insomnia, lack of appetite and other symptoms.

Now Prof. Yosef Sarne of Tel Aviv Univ.’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine says that the drug has neuroprotective qualities as well. He has found that extremely low doses of THC — the psychoactive component of marijuana — protects the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures or toxic drugs. Brain damage can have consequences ranging from mild cognitive deficits to severe neurological damage.

Previous studies focused on injecting high doses of THC within a very short time frame — approximately 30 minutes — before or after injury. Sarne’s current research, published in the journals Behavioural Brain Research and Experimental Brain Research, demonstrates that even extremely low doses of THC — around 1,000 to 10,000 times less than that in a conventional marijuana cigarette — administered over a wide window of one to seven days before or one to three days after injury can jumpstart biochemical processes which protect brain cells and preserve cognitive function over time.

This treatment, especially in light of the long time frame for administration and the low dosage, could be applicable to many cases of brain injury and be safer over time, Sarne says.”

More: http://www.laboratoryequipment.com/news/2013/05/marijuanas-thc-can-halt-brain-damage

Muscular Dystrophy-Cannabinoids-Symptom Relief

“Cannabinoids Help Muscular Dystrophy Symptoms: Cannabinoids are now known to have the capacity for neuromodulation, via direct, receptor-based mechanisms, at numerous levels within the nervous system. 

These provide therapeutic properties that may be applicable to the treatment of neurological disorders, including anti-oxidative, neuroprotective effects, analgesia, anti-inflammatory actions, immunomodulation, modulation of glial cells and tumor growth regulation. 

Beyond that, the cannabinoids have also been shown to be “remarkably safe with no potential for overdose.”

(vaporizing) Marijuana:

“miraculously improved his quality of life so much so that he left his family and friends in New Jersey to live in California, where he can readily get his medication.”

Sublingual (under the tongue)-tincture (alcohol based) or infused oil (olive or food grade glycerin or coconut)

Topicals (salves, ointments, balms) for muscle pain and spasms.

Cannabinoids:  increase appetite, analgesic (rid pain), muscle relaxant, saliva reduction, bronchodialation,  and sleep induction.

 

CBD-rich strains are best choice.  Sativa dominant x Indica.”

More: http://medicalmarijuana.com/medical-marijuana-treatments/MD

[Cannabinoids in multiple sclerosis — therapeutically reasonable?].

“For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies. Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS.

Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS.

 Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms.

 Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties. However, results from clinical trials do not allow the recommendation for the general use of cannabinoids in MS.

This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS”

http://www.ncbi.nlm.nih.gov/pubmed/16052440

Update on the Role of Cannabinoid Receptors after Ischemic Stroke

“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

“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

“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

“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

“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.

“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