Δ9-Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors

Posted on May 2, 2017 by David

“It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage.

In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB₁) agonist, Δ⁹-tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil.

Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB₁ and opioid receptors.

Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.

There is some evidence from experiments with mice that increasing anandamide or 2-arachidonoyl glycerol content may lead to neuroprotection.

Collectively, our data demonstrate that AM 404 and THC protect against neuronal ischaemia-induced injury through a mechanism involving cannabinoid and opioid receptors but not vanilloid receptors.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189998/

CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.

Posted on March 4, 2017 by David

“The role of CB2 cannabinoid receptors (CB₂R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved.

The aim of this study was to evaluate the involvement of CB₂R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved.

Our results indicate that CB₂R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.”

https://www.ncbi.nlm.nih.gov/pubmed/28253997

Cannabidiol Prevents Cerebral Infarction Via a Serotonergic 5-Hydroxytryptamine1A Receptor–Dependent Mechanism

Posted on February 23, 2017 by David

Image result for stroke journal

“Cannabis contains ≈80 different cannabinoids, including the psychoactive component Δ⁹-tetrahydrocannabinol, and nonpsychoactive components, which include cannabidiol, cannabinol, and cannabigerol.

In those components, cannabidiol, a nonpsychoactive constituent of cannabis, was found to be an anticonvulsant in animal models of epilepsy and in humans with epilepsy. Moreover, cannabidiol has been shown to have antispasmodic, anxiolytic, antinausea, and antirheumatoid arthritic properties. In addition, cannabidiol has been shown to be protective against global and focal ischemic injury.

Cannabidiol has been reported to be a neuroprotectant, but the neuroprotective mechanism of cannabidiol remains unclear. We studied the neuroprotective mechanism of cannabidiol in 4-hour middle cerebral artery (MCA) occlusion mice.

Cannabidiol significantly reduced the infarct volume induced by MCA occlusion in a bell-shaped curve. Similarly, abnormal cannabidiol but not anandamide or methanandamide reduced the infarct volume.

Cannabidiol and abnormal cannabidiol reduced the infarct volume.

These results suggested that the neuroprotective effect of cannabidiol may be related to the increase in CBF through the serotonergic 5-HT_1A receptor.”

http://stroke.ahajournals.org/content/36/5/1071

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

Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

Posted on February 23, 2017 by David

fx1

“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury.

In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line.

This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

Cannabidiol (CBD) is a nonpsychoactive cannabinoid derived from Cannabis sativa and a weak CB1 and CB2 cannabinoid receptor antagonist, with very low toxicity for humans. It has recently been demonstrated in vivo and in vitro that CBD has a variety of therapeutic properties, exerting antidepressant, anxiolytic, anti-inflammatory, immunomodulatory, and neuroprotective effects. Our results provide novel insight into the neuroprotective properties of CBD, which involves the regulation of the mitochondrial bioenergetics and the glucose metabolism of hippocampal neurons during OGD/R injury.

In summary, our results suggest that CBD exerts a potent neuroprotective effect against ischemia/reperfusion injury by attenuating intracellular oxidative stress, enhancing mitochondrial bioenergetics, and optimizing glucose metabolism via the pentose-phosphate pathway, thus strengthening the antioxidant defenses and preserving the energy homeostasis of neurons. More in-depth studies are required to investigate the precise mechanism underlying the success of CBD treatment and to determine the actual role of CBD in cerebral ischemia.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247568/

“Cannabidiol may soon be used in the emergency room to fight effects of stroke and cardiac emergencies” http://www.naturalnews.com/2017-02-21-cannabidiol-may-soon-be-used-in-the-emergency-room-to-fight-effects-of-stroke-cardiac-emergencies.html

β-Caryophyllene/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway.

Posted on February 6, 2017 by David

“This work was conducted to prepare β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex (HPβCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats.

Overall, the findings demonstrated the protective effects of HPβCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPβCD/BCP in the therapy of vascular dementia in the future.”

https://www.ncbi.nlm.nih.gov/pubmed/28154534

“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

“Cyclodextrin” https://en.wikipedia.org/wiki/Cyclodextrin

Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.

Posted on January 23, 2017 by David

Image result for Redox Biol.

“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury.

In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line.

This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.”

https://www.ncbi.nlm.nih.gov/pubmed/28110213

Cannabis, Tobacco, Alcohol Use, and the Risk of Early Stroke

Posted on January 3, 2017 by David

Image result for ahajournals

“Current knowledge on cannabis use in relation to stroke is based almost exclusively on clinical reports. By using a population-based cohort, we aimed to find out whether there was an association between cannabis use and early-onset stroke, when accounting for the use of tobacco and alcohol.

Conclusions—We found no evident association between cannabis use in young adulthood and stroke, including strokes before 45 years of age. Tobacco smoking, however, showed a clear, dose–response shaped association with stroke.”

http://stroke.ahajournals.org/content/early/2016/12/27/STROKEAHA.116.015565

“New Study: Cigarettes Tied To Increased Stroke Risk But Not Marijuana” http://www.weednews.co/new-study-cigarettes-tied-to-increased-stroke-risk-but-not-marijuana/

Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia.

Posted on November 28, 2016 by David

Image result for Prog Neuropsychopharmacol Biol Psychiatry.

“This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice.

Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21).

Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO.

In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels.

CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals.

Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.”

https://www.ncbi.nlm.nih.gov/pubmed/27889412

Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia.

Posted on November 20, 2016 by David

Image result for Eur J Pharmacol.

“Excitotoxicity and imbalance of sodium and calcium homeostasis trigger pathophysiologic processes in cerebral ischemia which can accelerate neuronal death.

Neuroprotective role of cannabidiol (CBD), one of the main non-psychoactive phytocannabinoids of the cannabis plant, has attracted attention of many researchers in the neurodegenerative diseases studies.

The present investigation was designed to determine whether cannabidiol can alleviate the severity of ischemic damages and if it is able to exert its anti-excitotoxic effects through sodium and calcium regulation.

The present results indicate that administration of cannabidiol (100 and 200 ng/rat) in the MCAO-induced cerebral ischemia caused a remarkable reduction in neurological deficit, infarction, brain edema, and BBB permeability in comparison with the vehicle group. Up-regulation of NCX2 and NCX3 in cannabidiol-received groups was also observed.

These findings support the view that the reduction of ischemic injuries elicited by cannabidiol can be at least partly due to the enhancement of NCX protein expression and its cerebro-protective role in those cerebral territories supplied by MCA.”

https://www.ncbi.nlm.nih.gov/pubmed/27856160

Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid.

Posted on September 7, 2016 by David

Image result for J Pharmacol Exp Ther

“Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis.

Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFalpha) production after head injury. In the present study, we demonstrate the ability of HU-211 to suppress TNFalpha production and to rescue mice and rats from endotoxic shock after LPS (Escherichia coli 055:B5) inoculation.

Administration of LPS to Sprague-Dawley rats resulted in a 30% reduction in the mean arterial blood pressure within 30 min, which persisted for 3 hr. HU-211, given 2 to 3 min before LPS, completely abolished the typical hypotensive response. Furthermore, the drug also markedly suppressed in vitro TNFalpha production and nitric oxide generation (by >90%) by both murine peritoneal macrophages and rat alveolar macrophage cell line exposed to LPS.

HU-211 may, therefore, have therapeutic implications in the treatment of TNFalpha-mediated pathologies.”

http://www.ncbi.nlm.nih.gov/pubmed/9353414