Cannabinoid receptor 1 deficiency in a mouse model of Alzheimer’s disease leads to enhanced cognitive impairment despite of a reduction in amyloid deposition.

“Alzheimer’s disease (AD) is characterized by amyloid-β deposition in amyloid plaques, neurofibrillary tangles, inflammation, neuronal loss, and cognitive deficits. Cannabinoids display neuromodulatory and neuroprotective effects and affect memory acquisition. Here, we studied the impact of cannabinoid receptor type 1 (CB1) deficiency on the development of AD pathology…

…the findings indicate that CB1 deficiency can worsen AD-related cognitive deficits and support a potential role of CB1 as a pharmacologic target.”

http://www.ncbi.nlm.nih.gov/pubmed/23838176

WIN55212-2 attenuates amyloid-beta-induced neuroinflammation in rats through activation of cannabinoid receptors and PPAR-γ pathway.

“Cannabinoids have been shown to exert neuroprotective effects in a plethora of neurodegenerative conditions.

Over the past decade, some studies demonstrate that cannabinoids can interact with nuclear peroxisome proliferator-activated receptors (PPARs).We investigated protective properties of WIN55212-2 (WIN, a non-selective cannabinoid receptor agonist) in beta-amyloid (Aβ)-induced neurodegeneration in rat hippocampus and possible involvement of PPAR-gamma (PPAR-γ). Aβ (1-42) was injected into the hippocampus of male rats. Animals were administered by intracerebroventricular rout the following treatments on days 1, 3, 5, 7: vehicle, WIN, GW9662 (selective PPAR-γ antagonist) plus WIN, AM251 (selective CB₁ receptor antagonist) plus WIN, SR144528 (selective CB₂ receptor antagonist) plus WIN, each of antagonists alone. Injection of Aβ-induced spatial memory impairment and a dramatic rise in hippocampal TNF-α, active caspase 3, nuclear NF-kB levels and TUNEL-positive neurons. WIN administration significantly improved memory function and diminished the elevated levels of these markers, while antagonizing either CB₁ or CB₂ receptor subtype partially attenuated the protective effects. Intriguingly, WIN significantly increased PPAR-γ level and transcriptional activity, the latter being partially inhibited with AM251 but not with SR144528. The enhancing effect on PPAR-γ pathway was crucial to WIN-induced neuroprotection since GW9662 partially reversed the beneficial actions of WIN. Co-administration of the three antagonists led to the complete abrogation of WIN effects.

Our findings indicate that WIN exerts neuroprotective and anti-inflammatory actions against Aβ damage through both CB₁ and CB₂ receptors. Of great note, both direct and CB₁-mediated increase in PPAR-γ signaling also contributes to WIN-induced neuroprotection.”

http://www.ncbi.nlm.nih.gov/pubmed/22634229

Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions.

“Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects

…Together, these results suggest that pharmacological CB2R ligands offer a new strategy for BBB protection during neuroinflammation.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325902/

Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1 neuropathogenesis.

“Anti-retroviral therapy (ART) has had a tremendous impact on the clinical outcomes of HIV-1 infected individuals. While ART has produced many tangible benefits, chronic, long-term consequences of HIV infection have grown in importance. HIV-1-associated neurocognitive disorder (HAND) represents a collection of neurological syndromes that have a wide range of functional cognitive impairments. HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1.

Based upon work in other models of neuroinflammation, kappa opioid receptors (KOR) and synthetic cannabinoids have emerged as having neuroprotective properties and the ability to dampen pro-inflammatory responses of glial cells; properties that may have a positive influence in HIV-1 neuropathogenesis. The ability of KOR ligands to inhibit HIV-1 production in human microglial cells and CD4 T lymphocytes, demonstrate neuroprotection, and dampen chemokine production in astrocytes provides encouraging data to suggest that KOR ligands may emerge as potential therapeutic agents in HIV neuropathogenesis.

 Based upon findings that synthetic cannabinoids inhibit HIV-1 expression in human microglia and suppress production of inflammatory mediators such as nitric oxide (NO) in human astrocytes, as well as a substantial literature demonstrating neuroprotective properties of cannabinoids in other systems, synthetic cannabinoids have also emerged as potential therapeutic agents in HIV neuropathogenesis.

This review focuses on these two classes of compounds and describes the immunomodulatory and neuroprotective properties attributed to each in the context of HIV neuropathogenesis.”

http://www.ncbi.nlm.nih.gov/pubmed/21850403

Cannabidiol (CBD): Fighting Inflammation & Aggressive Forms of Cancer

“Marijuana contains at least 60 known chemicals called cannabinoids, which activate cannabinoid receptors in your body. Tetrahydrocannabinol, or THC, is the main component responsible for the psychoactive effects, or “high,” marijuana is known for. While THC is known to have some medicinal value, there has been recent investigation into a new cannabinoid that is rumored to have more medicinal benefits than any single pharmaceutical drug on the market.”

“What is Cannabidiol (CBD)?

This cannabinoid is known as Cannabidiol (CBD), and is the second most abundant cannabinoid in cannabis. Research done by G.W. Pharmaceuticals suggests that CBD could be used for treating symptoms of rheumatoid arthritis and other autoimmune diseases, diabetes, nausea, bowel disorders, and many other hard-to-control side effects. According to an article from Projectcbd.com, CBD has even demonstrated neuroprotective effects, and its anti-cancer potential is currently being explored.

While it was originally believed that THC is a breakdown product of CBD, it is now known that both THC and CBD are actually metabolites of their decarboxylated acidic forms, THCa and CBDa. These acidic precursors are decarboxylated (essentially dried) by heat or extraction to produce THC and CBD; only then do they become psychoactive. The compound has medicinal benefits without the “high” that some patients do not desire. This makes CBD appealing to patients who are looking for an alternative to their current meds, which often have opiate-like effects.”

More: http://www.medicaljane.com/2012/12/20/cannabidiol-cbd-medicine-of-the-future/

Study: Cannabis may prevent brain damage – FOX

“Marijuana continues to be a paradox as it makes its way from illicit drug to wonder medicine being used to treat a number of symptoms and disorders more safely than traditional pharmaceuticals.”

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“In the latest news, cannabis, which has been associated with long-term cognitive deficits in chronic users, is now being tested as a treatment to preserve brain function after traumatic injury.

…some reports have shown that cannabis has neuroprotective effects. Studies have suggested that it has protective effects in neurodegenerative diseases like multiple sclerosis, Alzheimer’s, Huntington’s and Parkinson’s diseases.”

More: http://www.foxnews.com/health/2013/06/06/study-cannabis-may-prevent-brain-damage/

Read more: http://www.foxnews.com/health/2013/06/06/study-cannabis-may-prevent-brain-damage/#ixzz2VXJJw9yc

Marijuana component can halt brain damage – MSN

“Extremely low doses of THC – the psychoactive component of marijuana – protects the brain from long-term cognitive damage in case of injury from hypoxia (lack of oxygen), seizures, or toxic drugs, a new study has claimed.

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, Professor Yosef Sarne of Tel Aviv University”s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine in US found the drug has neuroprotective qualities as well.

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 jump start 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 said.

While performing experiments on the biology of cannabis, researchers found that low doses of the drug had a big impact on cell signalling, preventing cell death and promoting growth factors.

This finding led to a series of experiments designed to test the neuroprotective ability of THC in response to various brain injuries.

In the lab, the researchers injected mice with a single low dose of THC either before or after exposing them to brain trauma. A control group of mice sustained brain injury but did not receive the THC treatment.

When the mice were examined 3 to 7 weeks after initial injury, recipients of the THC treatment performed better in behavioural tests measuring learning and memory.

Additionally, biochemical studies showed heightened amounts of neuroprotective chemicals in the treatment group compared to the control group.

The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers concluded.”

More: http://news.in.msn.com/international/article.aspx?cp-documentid=253106176

Brain Damage can be Prevented by Low Doses Of Marijuana – MedIndia

“Researchers at Tel Aviv University have 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.

The current research by Prof. Yosef Sarne of Tel Aviv University’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine 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, Prof. Sarne said.

While performing experiments on the biology of cannabis, Prof. Sarne and his fellow researchers discovered that low doses of the drug had a big impact on cell signalling, preventing cell death and promoting growth factors. This finding led to a series of experiments designed to test the neuroprotective ability of THC in response to various brain injuries.

In the lab, the researchers injected mice with a single low dose of THC either before or after exposing them to brain trauma. A control group of mice sustained brain injury but did not receive the THC treatment. When the mice were examined 3 to 7 weeks after initial injury, recipients of the THC treatment performed better in behavioral tests measuring learning and memory. Additionally, biochemical studies showed heightened amounts of neuroprotective chemicals in the treatment group compared to the control group.

The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers concluded.

One explanation for this effect is pre- and post-conditioning, whereby the drug causes minute damage to the brain to build resistance and trigger protective measures in the face of much more severe injury, explained Prof. Sarne.

The low dosage of THC is crucial to initiating this process without causing too much initial damage.

According to Prof. Sarne, there are several practical benefits to this treatment plan. Due to the long therapeutic time window, this treatment can be used not only to treat injury after the fact, but also to prevent injury that might occur in the future.

For example, cardiopulmonary heart-lung machines used in open heart surgery carry the risk of interrupting the blood supply to the brain, and the drug can be delivered beforehand as a preventive measure. In addition, the low dosage makes it safe for regular use in patients at constant risk of brain injury, such as epileptics or people at a high risk of heart attack.

Prof. Sarne is now working in collaboration with Prof. Edith Hochhauser of the Rabin Medical Center to test the ability of low doses of THC to prevent damage to the heart. Preliminary results indicate that they will find the same protective phenomenon in relation to cardiac ischemia, in which the heart muscle receives insufficient blood flow.

His research findings were published in the journals Behavioural Brain Research and Experimental Brain Research.” 

 

THC Can Prevent Brain Damage – Study

“Marijuana became popular as a recreational drug and as its legalization movement became more popular, studies were conducted on its therapeutic properties. 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. But self-reported milder symptoms often claim that only marijuana helps…

Prof. Yosef Sarne in the Department of Physiology and Pharmacology at Tel Aviv University says that the drug can go beyond symptoms – it also has neuroprotective qualities. 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…

The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers conclude…

According to Sarne, there are several practical benefits to this treatment plan. Due to the long therapeutic time window, this treatment can be used not only to treat injury after the fact, but also to prevent injury that might occur in the future. For example, cardiopulmonary heart-lung machines used in open heart surgery carry the risk of interrupting the blood supply to the brain, and the drug can be delivered beforehand as a preventive measure. In addition, the low dosage makes it safe for regular use in patients at constant risk of brain injury, such as epileptics or people at a high risk of heart attack.

Sarne is now working with Prof. Edith Hochhauser of the Rabin Medical Center to test the ability of low doses of THC to prevent damage to the heart. Preliminary results indicate that they will find the same protective phenomenon in relation to cardiac ischemia, in which the heart muscle receives insufficient blood flow.”

More: http://www.science20.com/news_articles/thc_can_prevent_brain_damage_study-113512

Extremely low doses of THC protect the brain from long-term cognitive damage

Conditioning the brain. Extremely low doses of marijuana’s psychoactive component protect brain before and after injury, says Tel Aviv University researcher.

While performing experiments on the biology of cannabis, Prof. Sarne and his fellow researchers discovered that low doses of the drug had a big impact on cell signalling, preventing cell death and promoting growth factors. This finding led to a series of experiments designed to test the neuroprotective ability of THC in response to various brain injuries.

In the lab, the researchers injected mice with a single low dose of THC either before or after exposing them to brain trauma. A control group of mice sustained brain injury but did not receive the THC treatment. When the mice were examined 3 to 7 weeks after initial injury, recipients of the THC treatment performed better in behavioral tests measuring learning and memory. Additionally, biochemical studies showed heightened amounts of neuroprotective chemicals in the treatment group compared to the control group.”

More: http://www.news-medical.net/news/20130531/Extremely-low-doses-of-THC-protect-the-brain-from-long-term-cognitive-damage.aspx