Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.

The effect of THC was in part mediated by the cannabinoid receptor CB1.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…

In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models. 

This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

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

Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-d-aspartate-induced AF5 cell death.

Image result for delta-9-tetrahydrocannabinol

“One of the most promising potential medical applications of cannabinoids involves their ability to protect cells from a variety of toxic events.

Cannabinoids have been reported to protect neurons from death…

Cannabinoids, such as the pharmacologically active component of marijuana (-)Δ9-tetrahydrocannabinol (THC)…

The neuroprotective effects of Δ9-tetrahydrocannabinol (THC) were examined…

Protective effects of Delta(9)-tetrahydrocannabinol… THC may function as an antioxidant to increase cell survival… 

THC can produce receptor-independent neuroprotective or cellular protective effects at micromolar concentrations as a result of its antioxidant properties…

In conclusion, THC produces a potent neuroprotective effect…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824211/

Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity.

Image result for delta-9-tetrahydrocannabinol

“Excitotoxic neuronal death underlies many neurodegenerative disorders…

Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity…

…desensitization of CB(1) receptors diminishes the neuroprotective effects of cannabinoids.

This study demonstrates the importance of agonist efficacy and the duration of treatment on the neuroprotective effects of cannabinoids.

It will be important to consider these effects on neuronal survival when evaluating pharmacologic treatments that modulate the endocannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/17140550

“Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity” http://molpharm.aspetjournals.org/content/69/3/691.long

Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity

“Cannabinoids protect neurons from excitotoxic injury…

Endogenous or exogenous cannabinoids have shown neuroprotective effects…

The main finding reported here is that cannabinoids protect neurons from excitotoxic injury by a mechanism that involves the activation of CB1R and inhibition of NOS and PKA….

Cannabinoid receptor agonist drugs protect neurons…

By identifying the signaling pathways responsible for cannabinoid effects in animal models of disease and their human counterparts, it may be possible to design more specific and therefore more efficacious cannabinoid-based therapies.”

http://molpharm.aspetjournals.org/content/69/3/691.long

Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. http://www.ncbi.nlm.nih.gov/pubmed/17140550

Cannabinoids & Stress: Impact of HU-210 on behavioral tests of anxiety in acutely stressed mice.

“Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles.

Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs.

This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioural testing.

Exogenouscannabinoid administration induced distinct behavioural phenotypes in stressed and unstressed mice…

These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner.

This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.”

http://www.ncbi.nlm.nih.gov/pubmed/25707713

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

Hypothalamic POMC neurons promote cannabinoid-induced feeding.

“Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake.

Here we test whether CB1R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons.

We show that chemical promotion of CB1R activity increases feeding, and notably, CB1R activation also promotes neuronal activity of POMC cells…

Together, these results uncover a previously unsuspected role of POMC neurons in the promotion of feeding by cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/25707796

“Yale Study Finds “Marijuana Munchies” Linked to Brain Neurons”   http://wnpr.org/post/yale-study-finds-marijuana-munchies-linked-brain-neurons

“Mulling the marijuana munchies: How the brain flips the hunger switch” http://news.yale.edu/2015/02/18/mulling-marijuana-munchies-how-brain-flips-hunger-switch

“Effects Of Marijuana: Smoking Weed Gives You ‘The Munchies’ Because Of The Hunger Switch In Your Brain”  http://www.medicaldaily.com/effects-marijuana-smoking-weed-gives-you-munchies-because-hunger-switch-your-brain-322534

“Researchers discover truth about the munchies”                              http://www.west-info.eu/researchers-discover-truth-about-the-munchies/

Sativex in the management of multiple sclerosis-related spasticity: role of the corticospinal modulation.

“Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS).

This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement.

The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits…

Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms.

Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.”

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968

Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis.

“The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation.

Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor.

Importantly, the lead of this series (26, hCB2: K i = 0.39 nM, hCB1: K i > 3000 nM) was found to protect mice against experimental colitis after oral administration.”

http://www.ncbi.nlm.nih.gov/pubmed/25699149

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

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

“To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by proinflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).

CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases.

Cannabinoids can suppress inflammatory cytokines…

The levels of CB1 and CB2 can be up-regulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS”

http://www.ncbi.nlm.nih.gov/pubmed/25704169

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/