A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol

Posted on March 12, 2017 by David

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“Cannabidiol (CBD) is the second most abundant phytocannabinoid, after Δ⁹-tetrahydrocannabinol (THC) and was first isolated from the cannabis extract in 1940.

Given the increasing clinical use of CBD, and the numerous effects of CBD in the cardiovascular system, the aim of the present study was to systematically review and analyse in vivo studies evaluating the effects of CBD on alterations in haemodynamics.

From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke.

This meta-analysis and systematic review has highlighted the haemodynamic effects of CBD administration in vivo.

The positive effects induced by CBD include maintaining the fall in BP after global hypoxia, reducing the increase in MBP and HR post-stress, and increasing BF in ischaemia-reperfusion models.

It is possible that beneficial effects of CBD on haemodynamics occurs when the cardiovascular system is abnormally altered, suggesting that CBD may be used as a treatment for various cardiovascular disorders, such as hypertension, myocardial infarction and stroke.”

http://journal.frontiersin.org/article/10.3389/fphar.2017.00081/full

Inflammatory Regulation by Driving Microglial M2 Polarization: Neuroprotective Effects of Cannabinoid Receptor-2 Activation in Intracerebral Hemorrhage.

Posted on March 7, 2017 by David

“The cannabinoid receptor-2 (CB2R) was initially thought to be the “peripheral cannabinoid receptor.” Recent studies, however, have documented CB2R expression in the brain in both glial and neuronal cells, and increasing evidence suggests an important role for CB2R in the central nervous system inflammatory response.

Intracerebral hemorrhage (ICH), which occurs when a diseased cerebral vessel ruptures, accounts for 10-15% of all strokes. Although surgical techniques have significantly advanced in the past two decades, ICH continues to have a high mortality rate.

The aim of this study was to investigate the therapeutic effects of CB2R stimulation in acute phase after experimental ICH in rats and its related mechanisms.

These findings demonstrated that CB2R stimulation significantly protected the brain damage and suppressed neuroinflammation by promoting the acquisition of microglial M2 phenotype in acute stage after ICH.

Taken together, this study provided mechanism insight into neuroprotective effects by CB2R stimulation after ICH.”

https://www.ncbi.nlm.nih.gov/pubmed/28261199

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

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“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

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“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

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

Posted on January 3, 2017 by David

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“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 brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke.

Posted on December 26, 2016 by David

Neuropharmacology

“Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS).

Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke.

The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS.

RESULTS:

CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H⁺-MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation.

CONCLUSIONS:

CBD administration after Middle Cerebral Artery Occlusion (MCAO) led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/28012949

“Post-stroke administration of Cannabidiol (CBD) is neuroprotective in neonatal rats. CBD neuroprotection is sustained in the long term. CBD treatment led to functional recovery in both motor and sensorimotor domains. CBD modulated excitotoxicity, astrocyte dysfunction and microglial activation.”

https://www.sciencedirect.com/science/article/pii/S0028390816305810

Cannabinoid Type-2 Receptor Drives Neurogenesis and Improves Functional Outcome After Stroke.

Posted on December 3, 2016 by David

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“Stroke is a leading cause of adult disability characterized by physical, cognitive, and emotional disturbances. Unfortunately, pharmacological options are scarce.

The cannabinoid type-2 receptor (CB2R) is neuroprotective in acute experimental stroke by anti-inflammatory mechanisms.

CONCLUSIONS:

Our data support that CB2R is fundamental for driving neuroblast migration and suggest that an endocannabinoid tone is required for poststroke neurogenesis by promoting neuroblast migration toward the injured brain tissue, increasing the number of new cortical neurons and, conceivably, enhancing motor functional recovery after stroke.”

https://www.ncbi.nlm.nih.gov/pubmed/27899748

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

Posted on October 9, 2016 by David

“Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol.

It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury.

Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system.

In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent.

Of the CB₁ receptor-independent cannabis, the most important is CBD.

In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD.

In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.

The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.

In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.”

https://www.ncbi.nlm.nih.gov/pubmed/27713349

Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism.

Posted on July 29, 2016 by David

“We examined the neuroprotective mechanism of cannabidiol, non-psychoactive component of marijuana, on the infarction in a 4 h mouse middle cerebral artery (MCA) occlusion model in comparison with Delta(9)-tetrahydrocannabinol (Delta(9)-THC).

Both pre- and post-ischemic treatment with cannabidiol resulted in potent and long-lasting neuroprotection, whereas only pre-ischemic treatment with Delta(9)-THC reduced the infarction.

Unlike Delta(9)-THC, cannabidiol did not affect the excess release of glutamate in the cortex after occlusion.

Cannabidiol suppressed the decrease in cerebral blood flow by the failure of cerebral microcirculation after reperfusion and inhibited MPO activity in neutrophils.

Furthermore, the number of MPO-immunopositive cells was reduced in the ipsilateral hemisphere in cannabidiol-treated group.

Cannabidiol provides potent and long-lasting neuroprotection through an anti-inflammatory CB(1) receptor-independent mechanism, suggesting that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/17437545