A restricted population of CB1 cannabinoid receptors with neuroprotective activity.

“The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain…

The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/24843137

Targeting the Endocannabinoid System for Neuroprotection: A 19F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.

“Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection…
The endocannabinoid system has been implicated as a therapeutic target for analgesia, anti-emesis, and neuroprotection… These findings provide a potential new therapeutic modality for neuroprotection through dual inhibition of FAAH and anandamide carrier proteins…”

Figure 1

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

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Neuroprotection and reduction of glial reaction by cannabidiol treatment after sciatic nerve transection in neonatal rats.

“The clinical use of neurotrophic factors is difficult due to side effects and elevated costs, but other molecules might be effective and more easily obtained. Among them, some are derived from Cannabis sativa.

Cannabidiol (CBD) is the major non-psychotropic component found on the surface of such plant leaves.

The present study aimed to investigate the neuroprotective potential of CBD…

The present results show that CBD possesses neuroprotective characteristics that may, in turn, be promising for future clinical use.”

http://www.ncbi.nlm.nih.gov/pubmed/23981015

CB1 and CB2 Cannabinoid Receptor Antagonists Prevent Minocycline-Induced Neuroprotection Following Traumatic Brain Injury in Mice.

“Traumatic brain injury (TBI) and its consequences represent one of the leading causes of death in young adults. This lesion mediates glial activation and the release of harmful molecules and causes brain edema, axonal injury, and functional impairment. Since glial activation plays a key role in the development of this damage, it seems that controlling it could be beneficial and could lead to neuroprotective effects. Recent studies show that minocycline suppresses microglial activation, reduces the lesion volume, and decreases TBI-induced locomotor hyperactivity up to 3 months. The endocannabinoid system (ECS) plays an important role in reparative mechanisms and inflammation under pathological situations by controlling some mechanisms that are shared with minocycline pathways. We hypothesized that the ECS could be involved in the neuroprotective effects of minocycline. To address this hypothesis, we used a murine TBI model in combination with selective CB1 and CB2 receptor antagonists (AM251 and AM630, respectively). The results provided the first evidence for the involvement of ECS in the neuroprotective action of minocycline on brain edema, neurological impairment, diffuse axonal injury, and microglial activation, since all these effects were prevented by the CB1 and CB2 receptor antagonists.”

http://www.ncbi.nlm.nih.gov/pubmed/23960212

Regulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseases. A focus on traditional medicines and flavonoids.

“Herbal medicine has long been used to treat neural symptoms. Although the precise mechanisms of action of herbal drugs have yet to be determined, some of them have been shown to exert anti-inflammatory and/or anti-oxidant effects in a variety of peripheral systems.

 Now, as increasing evidence indicates that neuroglia-derived chronic inflammatory responses play a pathological role in the central nervous system, anti-inflammatory herbal medicine and its constituents are being proved to be a potent neuroprotector against various brain pathologies.

 Structural diversity of medicinal herbs makes them valuable source of novel lead compounds against therapeutic targets that are newly discovered by genomics, proteomics, and high-throughput screening.”

http://www.ncbi.nlm.nih.gov/pubmed/15956812

Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation.

“There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768535/

Activation of Cortical Type 2 Cannabinoid Receptors Ameliorates Ischemic Brain Injury, Study Suggests

“A new study published in the March issue of The American Journal of Pathology suggests that cortical type 2 cannabinoid (CB2) receptors might serve as potential therapeutic targets for cerebral ischemia.

Researchers found that the cannabinoid trans-caryophyllene (TC) protected brain cells from the effects of ischemia in both in vivo and in vitro animal models. In rats, post-ischemic treatment with TC decreased cerebral infarct size and edema. In cell cultures composed of rat cortical neurons and glia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R), TC decreased neuronal injury and mitochondrial depolarization, specifically through type 2 cannabinoid receptor (CB2R) pathways.

“To our knowledge, novel data presented in this study provide evidence for the first time supporting a previously unappreciated role of cortical CB2R, especially neuronal CB2Rs, in ischemia,” says lead investigator Won-Ki Kim, PhD, of the Department of Neuroscience, College of Medicine, Korea University in Seoul. “This study suggests that further investigation is warranted to establish the clinical usefulness of TC as a preventative and therapeutic agent for treatment of stroke.””

More: http://www.sciencedaily.com/releases/2013/02/130221141140.htm

New Study: Cannabinoids Protect the Brain and Heart From Injury

“Cannabis is in the news again for its purported medicinal benefits, with researchers in Israel last week indicating it may help prevent trauma to the brain in certain circumstances and may also help with cardiac problems. A few months ago an English pharmaceutical company that manufactures cannabinoids announced it was developing a new treatment for epilepsy using them.”

Los Angeles City Council Votes To Ban Medical Marijuana Dispensaries

“Prof. Yosef Sarne in the Adelson Center for the Biology of Addictive Diseases in the Department of Physiology and Pharmacology at Tel Aviv University says that cannabis has neuro-protective qualities. He has found that extremely low doses of tetrahydrocannabinol or THC- the psychoactive component of marijuana- can protect the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs.”

More: http://jewishbusinessnews.com/2013/06/09/new-study-cannabinoids-protect-the-brain-and-heart-from-injury/