Treatment with a Heme Oxygenase 1 Inducer Enhances the Antinociceptive Effects of µ-Opioid, δ-Opioid, and Cannabinoid 2 Receptors during Inflammatory Pain.

Posted on September 11, 2014 by David

“The administration of µ-opioid receptor (MOR), δ-opioid receptor (DOR), and cannabinoid 2 receptor (CB2R) agonists attenuates inflammatory pain.

We investigated whether treatment with the heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the local effects and expression of MOR, DOR, or CB2R during chronic inflammatory pain…

This study shows that the HO-1 inducer (CoPP) increased the local antinociceptive effects of MOR, DOR, and CB2R agonists during inflammatory pain by altering the peripheral expression of MOR and DOR.

Therefore, the coadministration of CoPP with local morphine, DPDPE, or JWH-015 may be a good strategy for the management of chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25204546

Cannabinoid CB2 receptor (CB2R) stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord hemisection by ERK1/2 inactivation.

Posted on September 5, 2014 by David

“Spinal cord injury (SCI) is a devastating condition… Modulation of the endocannabinoid system (ECS) counteracts neurodegeneration, and pharmacological modulation of type-2 cannabinoid receptor (CB2R) is a promising therapeutic target for several CNS pathologies, including SCI…

These findings implicate the ECS, particularly CB2R, as part of the endogenous neuroprotective response that is triggered after SCI.

Thus, CB2R modulation might represent a promising therapeutic target that lacks psychotropic effects and can be used to exploit ECS-based approaches to counteract neuronal degeneration.”

http://www.ncbi.nlm.nih.gov/pubmed/25188514

http://www.thctotalhealthcare.com/category/spinal-cord-injury/

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease.

Posted on August 18, 2014 by David

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“Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders… Cannabinoids may also offer neuroprotection in Huntington’s disease (HD)…

Here, we examined this hypothesis in a rat model ofHuntington’s disease (HD)…

Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed…

…neuroprotection was attained exclusively with antioxidant cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC; or cannabidiol (CBD)…

In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-alpha.

Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/

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

Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity.

Posted on August 18, 2014 by David

Brain

“Cannabinoid-derived drugs are promising agents for the development of novel neuroprotective strategies.

…in Huntington’s disease there is a very early downregulation of CB₁ receptors in striatal neurons that, together with the undesirable psychoactive effects triggered by CB₁ receptor activation, foster the search for alternative pharmacological treatments.

These findings support a pivotal role for CB₂ receptors in attenuating microglial activation and preventing neurodegeneration that may pave the way to new therapeutic strategies for neuroprotection in Huntington’s disease as well as in other neurodegenerative disorders with a significant excitotoxic component.

Overall, the reduction of neuronal CB₁ receptors and the upregulation of microglial CB₂ receptors support a crucial role for the ECB system in the pathogenesis of Huntington’s disease.

The use of drugs targeting the ECB system via CB₁ receptors aimed at restoring neurochemical alterations and palliating symptoms might constitute an interesting strategy for the management of Huntington’s disease and other neurodegenerative disorders with a significant excitotoxicity component.”

http://brain.oxfordjournals.org/content/132/11/3152.long

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

Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease.

Posted on August 18, 2014 by David

“Here, we show that the genetic deletion of CB2 receptors in a slowly progressing HD mouse model accelerates the onset of motor deficits and increases their severity.

Treatment of mice with a CB2 receptor agonist extends life span and suppresses motor deficits, synapse loss, and CNS inflammation…

CB2 receptor signaling in peripheral immune cells suppresses neurodegeneration in HD mouse models

The development of peripherally restricted CB2 receptor agonists holds promise for treating HD and other neurodegenerative diseases.

In summary, our results suggest CB2 receptor signaling in peripheral immune cells has an important role in HD and other neurodegeneration disorders. Further elucidation of the molecular mechanisms that underlie these effects may lead to novel therapeutic strategies to treat these disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753072/

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

Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.

Posted on July 27, 2014 by David

Figure 1.

“To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology…

Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1…

…our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death.

CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).”

http://www.fasebj.org/content/22/10/3685.long

Mechanisms of control of neuron survival by the endocannabinoid system.

Posted on July 6, 2014 by David

“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.

Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.

Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.

Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.

Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/18781978

Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington’s disease brain.

Posted on July 1, 2014 by David

“Huntington’s disease (HD) is an inherited neurological disease with motor, cognitive and psychiatric symptoms. Characterised by neuronal degeneration, HD pathology is initially apparent in the striatum and cortex.

Considerable research has recently suggested that the neurological immune response apparent in brain injury and disease may provide a valuable therapeutic target.

Cannabinoid CB2 receptors are localised and up-regulated on a number of peripheral immune cell types following inflammation and injury.

…our observation that CB2 is present on blood vessel cells, with increased CD31 co-localisation in HD may represent a new context for CB2 therapeutic approaches to neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24978314

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

Activation of cannabinoid 2 receptors protects against cerebral ischemia by inhibiting neutrophil recruitment

Posted on June 24, 2014 by David

Figure 1.

“THE CONSEQUENCES OF ISCHEMIC INJURY in liver, heart, and brain can be ameliorated by cannabinoids, a group of diverse compounds that include constituents of the plant Cannabis sativa (phytocannabinoids), endogenous lipids (endocannabinoids), and synthetic substances. Most of the effects of cannabinoids are mediated by the G-protein-coupled receptors cannabinoid receptor 1 (CB₁) and cannabinoid receptor 2 (CB_2)…

Cannabinoids protect against ischemic stroke…

Activation of the cannabinoid 2 receptor (CB₂) reduces ischemic injury in several organs…

In conclusion, our data demonstrate that by activating p38 in neutrophils, CB₂ agonists inhibit neutrophil recruitment to the brain and protect against ischemic brain injury.”

http://www.fasebj.org/content/24/3/788.long

Cannabis gives stroke patients hope

Posted on June 24, 2014 by David

“New research by University of Otago scientists suggests some mechanisms in the brain targeted by cannabis could become drugs targets to counter brain cell damage after a stroke.

Researchers from the Medical School’s Department of Pharmacology and Toxicology have been the first in the world to show the cannabinoid CB2 receptor appears in the rat brain following a stroke. Their findings were published recently in the journal Neuroscience Letters.

Dr John Ashton says the CB2 receptor is a protein produced as part of the body’s immune response system.

“This response is triggered by stroke and causes the inflammation that leads to damage in the area of the brain around where the stroke has occurred.

“If the inflammation can be stopped or reduced then it offers the hope of reducing the extent of the damage caused by stroke – and CB2 offers a potential target for such a drug.””

http://www.sciencealert.com.au/news/20071404-15007.html

“Cerebral hypoxia-ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain. The presence of CB2-positive cells in the brain following stroke may provide a novel strategy for cannabinoid-mediated intervention into stroke induced neurodegeneration without the psychoactive effects of CB1 receptor stimulation.” https://www.ncbi.nlm.nih.gov/pubmed/17123706