The Endocannabinoid System as a Therapeutic Target in Glaucoma.

Posted on February 18, 2016 by David

“Glaucoma is an irreversible blinding eye disease which produces progressive retinal ganglion cell (RGC) loss. Intraocular pressure (IOP) is currently the only modifiable risk factor, and lowering IOP results in reduced risk of progression of the disorder.

The endocannabinoid system (ECS) has attracted considerable attention as a potential target for the treatment of glaucoma, largely due to the observed IOP lowering effects seen after administration of exogenous cannabinoids.

However, recent evidence has suggested that modulation of the ECS may also be neuroprotective.

This paper will review the use of cannabinoids in glaucoma, presenting pertinent information regarding the pathophysiology of glaucoma and how alterations in cannabinoid signalling may contribute to glaucoma pathology.

Additionally, the mechanisms and potential for the use of cannabinoids and other novel agents that target the endocannabinoid system in the treatment of glaucoma will be discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/26881140

http://www.thctotalhealthcare.com/category/glaucoma-2/

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease.

Posted on February 18, 2016 by David

“The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago.

In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma.

The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss.

Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness.

The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26881135

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

Posted on February 18, 2016 by David

“Cannabis is one of the most prevalent drugs used in industrialized countries.

The main effects of Cannabis are mediated by two major exogenouscannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2.

Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes.

This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system.

As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology.

This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection.

Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases.

Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.”

http://www.ncbi.nlm.nih.gov/pubmed/26881099

Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier.

Posted on February 17, 2016 by David

“The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection.

The blood-brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention.

Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cell death (CB1), inflammation (CB2) and oxidative stress (possibly CB independent)-all processes that also damage the BBB.

Several examples of CB-mediated protection of the BBB have been found, such as inhibition of leukocyte influx and induction of amyloid beta efflux across the BBB.

Moreover, the CB receptors were shown to improve BBB integrity, particularly by restoring the tightness of the tight junctions. This review demonstrated that both CB receptors are able to restore the BBB and neuroprotection, but much uncertainty about the underlying signaling cascades still exists and further investigation is needed.”

http://www.ncbi.nlm.nih.gov/pubmed/24929655

Neuroprotective effects of the synthetic cannabinoid HU-210 in primary cortical neurons are mediated by phosphatidylinositol 3-kinase/AKT signaling.

Posted on February 17, 2016 by David

“Cannabinoids (CBs) are neuroprotective in vivo and in vitro.

…the PI 3-K/AKT signaling pathway mediates the neuroprotective effect of exogenous cannabinoids in primary CNS neurons.”

http://www.ncbi.nlm.nih.gov/pubmed/15607953

Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling

Posted on February 17, 2016 by David

Image result for the journal of neuroscience logo

“Cannabinoids exert pleiotropic actions in the CNS, including the inhibition of inflammatory responses and the enhancement of neuronal survival after injury… cannabinoid receptors are distributed widely in brain… Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling.

Limited clinical studies have suggested that cannabis might ameliorate the symptomatology in multiple sclerosis patients, and beneficial effects of synthetic cannabinoids have been reported in vivoin rodent models of multiple sclerosis.

Apart from their actions on motor and pain pathways, cannabinoids regulate the immune response by reducing the production of inflammatory mediators by leukocytes, astrocytes, and microglia, which may contribute to their beneficial effects.

The results of the present study also point to a direct role of cannabinoids in promoting the survival of oligodendrocyte progenitors, particularly in unfavorable conditions, as would be the case in demyelinating diseases. Studies in progress are aimed to evaluate the function of cannabinoids in other models affecting oligodendroglial survival.

http://www.jneurosci.org/content/22/22/9742.long

Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report.

Posted on February 11, 2016 by David

“This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits.

The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects.

The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use.

With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26807069

Peripubertal treatment with cannabidiol prevents the emergence of psychosis in an animal model of schizophrenia

Posted on February 10, 2016 by David

“Currently, the pharmacotherapy of schizophrenia is still associated with significant side effects and high rates of treatment resistance, causing a great deal of suffering to patients and their caregivers. Developing safe interventions able to prevent the emergence of full-blown psychosis would therefore represent a major advance.

Cannabidiol (CBD) is a non-psychotomimetic compound of Cannabis sativa that presents antipsychotic properties in animal models and humans.

However, despite the growing evidence of CBD’s neuroprotective effects and therapeutic application in schizophrenia, so far no study has addressed its potential as a preventive intervention.”

http://www.schres-journal.com/article/S0920-9964(16)30060-3/abstract

http://www.thctotalhealthcare.com/category/schizophrenia/

The molecular mechanism and effect of cannabinoid-2 receptor agonist on the blood-spinal cord barrier permeability induced by ischemia-reperfusion injury.

Posted on February 3, 2016 by David

“Previous studies have shown that modulation of the receptor-mediated endocannabinoid system during ischemia injury can induce potent neuroprotective effects.

However, little is known about whether cannabinoid-2 (CB2) receptor agonist would produce a protective effect on blood-spinal cord barrier (BSCB) during ischemia.

Taken together, all of these results suggested that JWH-015 might regulate the BSCB permeability and this effect could be related to paracellular and transcellular pathway.

And pharmacological CB2R ligands offer a new strategy for BSCB protection during ischemic injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26835555

Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures.

Posted on February 2, 2016 by David

“Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile.

β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity.

In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects.

Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice.

Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/26827298

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934