Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.

“Experimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine.

Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception.

…recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain…

In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine…


These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”

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Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

“… we have reported here for the first time the potent and efficacious modulatory effects by some phytocannabinoids on TRPA1- and TRPM8-mediated [Ca2+]ielevation…

Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.”

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The endocannabinoid system, cannabinoids, and pain.

“The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation… Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions.

Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints.

 However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles.

This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.”

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Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial.

“Clinical reports indicate that cannabinoids may alleviate pain in different pain conditions, including multiple sclerosis related pain…

Randomised double blind placebo controlled crossover trial… To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis…


Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.”

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Anandamide deficiency and heightened neuropathic pain in aged mice.

“Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly. We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.

We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.

 R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.

Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.

This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury…”


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Controlling 2-arachidonoylglycerol metabolism as an anti-inflammatory strategy.

“The endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation.

 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is dependent on its endogenous levels, which are tightly controlled by several hydrolases, monoacylglycerol lipase and α/β-hydrolase domain 6 and 12.

 Moreover, 2-AG is also a substrate of cyclooxygenase-2, and this reaction leads to the formation of prostaglandin glycerol esters, the effects of which remain to be fully elucidated.

 In this review we discuss the multiple mechanisms by which 2-AG controls inflammation and the therapeutic potential of 2-AG metabolism inhibitors.”

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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.”


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Marijuana May Help Fight Brain Damage

“Marijuana may actually help protect the brain against injury, a new study suggests.”

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“While marijuana is most commonly known as a recreational drug, an increasingly number of studies show that the plant has many therapeutic qualities like relieving pain, insomnia, lack of appetite and other symptoms associated with conditions like cancer and PTSD.

Now a new study reveals that very low doses of Tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, may protect the brain from long-term cognitive damage in the wake of injury from hypoxia, seizures or toxic drugs.”


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Cannabinoids Attenuate Cancer Pain and Proliferation in a Mouse Model

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“Oral cancer represents 3% of all cancers and its overall survival rate of 50% places it among the worst of all cancers

For many years cannabinoids have been used for medicinal and recreational purposes.

Recently, studies have focused on the therapeutic effects of cannabinoids on different cancers. The current study was the first to investigate the therapeutic effects of synthetic cannabinoids on oral cancer.

We investigated the effects of cannabinoid receptor agonists on (1) oral cancer cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse cancer model.

Here we demonstrate the anti-nociceptive and anti-proliferative effects of systemic administration of cannabinoid receptor agonists on human oral cancer cells.

Our results suggest that systemic administration of cannabinoids decease oral cancer pain.

Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation.

The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer.

The present findings suggest that cannabinoid treatment may be a promising alternative therapy for oral cancer pain management. Furthermore, CBr2 agonism is not only palliative, but it may also be effective in inhibiting oral cancer growth, making the agonist a particularly desirable therapeutic agent.”

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Marijuana mouth spray for cancer patients tough to abuse – NBC

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“The medical marijuana drug Sativex, which could be approved in the United States in the coming years as a treatment for pain relief, has little potential for abuse, experts say.

The British pharmaceutical company GW Pharmaceuticals is currently testing the drug, which is delivered as a mouth spray and called Sativex, in clinical trials. The company plans to seek U.S. Food and Drug Administration approval for the drug as a treatment for cancer pain when the trials are completed, likely sometime in 2014, a spokesperson for GW Pharmaceuticals told MyHealthNewsDaily.

The active ingredients in Sativex, known as cannabinoids, are derived from the cannabis plant. It is the first marijuana-based drug to be made by extracting the compounds from the plant, rather than synthesizing them. Two other drugs, Marinol and Cesamet, based on synthetic cannabinoids, were approved by the FDA in the 1980s.”


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