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

Getting High on the Endocannabinoid System

“The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health.

Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind.

By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.

…either stimulating or inhibiting the endocannabinoid system could have beneficial effects.

The most direct route of THC administration is by smoking marijuana or other forms of cannabis. Yet purified, FDA-approved medicinal preparations of THC are available in pill form… Why not just take a pill? There are several reasons that some patients prefer puffing over swallowing. One quantitatively minor factor is potential lethality.

It is possible to get a fatal overdose by swallowing too many THC pills at once, whereas documented evidence of death simply from smoking too much cannabis does not seem to exist.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/

The Health Benefits of Medical Cannabis

marijuanaplant

“Few people may know this but cannabis, or marijuana, had been popular as a remedy since ancient times.

It was in 2727 B.C. when there was the first record of its use in China. It was also familiar to ancient Greeks, Romans and people from the Middle East.

It was only during 1600 when cannabis use began to be regulated and restricted…

It was only recently that the public knew that cannabis has many benefits which were previously unknown to many people. Cannabis has been legalized in some states because it is non-toxic, can be moderately used by adults and has some beneficial effects on health.

Medical Cannabis

Medical cannabis is the term used to refer to the use of marijuana, cultivated with medical seeds, and other cannabinoid substances for treating health problems. Marijuana is a mixture of green, brown, crumpled and dried leaves from the marijuana plant. This mixture of leaves are rolled up and smoked like a cigar or cigarette or smoked through a pipe. It can also be mixed with food and eaten. Its mode of administration to the user includes vaporizing or smoking dried buds, consuming extracts and the ingestion of capsules. Synthetic cannabinoids are even available in some countries such as dronabinol and nabilone. While in some countries the recreational use of marijuana is illegal, in some countries its medical use is legal.”

http://www.doctortipster.com/19879-the-health-benefits-of-medical-cannabis.html

Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

“The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer.

The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors… Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models…

Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.

The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.”

http://www.ncbi.nlm.nih.gov/pubmed/24634659

“Considering the numerous complex pathological mechanisms involved in the progression of AD, treatments targeting a single causal or modifying factor offer limited benefit. Cannabinoids, however, exhibit pleiotropic activity, targeting in parallel several processes that play key roles in AD…”

Full: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

“Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation…Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.jneurosci.org/content/25/8/1904.long

Marijuana as a possible treatment for HIV and cancer

Marijuana

“There’s been some interesting research on using THC (tetrahydrocannabinol), the principal psychoactive drug in marijuana, to help fight HIV, and damage cancer cells in some leukemias and possibly malignant tumors.

…the possibility exists that information from both of these research studies may produce beneficial results in the treatment of HIV and cancer.”

More: http://americablog.com/2014/02/marijuana-treatment-hiv-cancer.html

Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’

“Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the ‘runner’s high’, which may function to encourage habitual aerobic exercise. Endocannabinoids (eCBs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise…”

Recent work supports direct links between eCB signaling and exercise in humans…

It is possible that neurobiological rewards induced by eCB signaling are an ancient human trait that evolved to encourage aerobic activity, and that the rewards explain the evolution…

The fact that running, and endurance exercise in general, remains an enjoyable and psychologically beneficial recreational activity for tens of millions of humans today suggests that we still may respond to a neurobiological trait that evolved early in our lineage.”

http://jeb.biologists.org/content/215/8/1331.long

Physical activity and the endocannabinoid system: an overview.

“Recognized as a “disease modifier”, physical activity (PA) is increasingly viewed as a more holistic, cost-saving method for prevention, treatment and management of human disease conditions.

The traditional view that PA engages the monoaminergic and endorphinergic systems has been challenged by the discovery of the endocannabinoid system (ECS), composed of endogenous lipids, their target receptors, and metabolic enzymes.

Indeed, direct and indirect evidence suggests that the ECS might mediate some of the PA-triggered effects throughout the body.

Moreover, it is now emerging that PA itself is able to modulate ECS in different ways.

Against this background, in the present review we shall discuss evidence of the cross-talk between PA and the ECS, ranging from brain to peripheral districts and highlighting how ECS must be tightly regulated during PA, in order to maintain its beneficial effects on cognition, mood, and nociception, while avoiding impaired energy metabolism, oxidative stress, and inflammatory processes.”

http://www.ncbi.nlm.nih.gov/pubmed/24526057

Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB 2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model.

“The aim of this study was to characterize the influence of WIN 55,212-2 (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model…

These preclinical data would suggest that WIN in combination with clonazepam, phenobarbital and valproate is associated with beneficial anticonvulsant pharmacodynamic interactions in the mouse 6 Hz-induced psychomotor seizure test.”

http://www.ncbi.nlm.nih.gov/pubmed/24549572

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

Pro-resolution, protective and anti-nociceptive effects of a cannabis extract in the rat gastrointestinal tract.

“Cannabis is widely used for treating a number of gastrointestinal ailments…

In the present study, we tested the effects (in rats) of a simple extract of medicinal cannabis (called “MFF”) for its ability to promote resolution of colitis…

These results demonstrate that a simple extract of medicinal cannabis can significantly enhance resolution of inflammation and injury, as well as prevent injury, in the gastrointestinal tract. Interestingly, different cannabinoid receptors were involved in some of the effects. MFF may serve as the basis for a simple preparation of cannabis that would produce beneficial effects in the GI tract with reduced systemic toxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/23756391