“Rescue of Impaired metabotropic glutamate receptor 5 (mGluR5)-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats…
Restoring endocannabinoid signaling allows mGluR5 activation to increase infralimbic output hence inhibit pain behaviors and mitigate pain-related cognitive deficits.”
“Serious clinical liabilities associated with the prescription of opiates for pain control include constipation, respiratory depression, pruritus, tolerance, abuse, and addiction.
A recognized strategy to circumvent these side effects is to combine opioids with other antinociceptive agents.
The combination of opiates with the primary active constituent of cannabis, Δ9-tetrahydrocannabinol, produces enhanced antinociceptive actions, suggesting that cannabinoid receptor agonists can be opioid sparing…
Here, we tested whether elevating the endogenous cannabinoid 2-arachidonylglycerol (2-AG) through the inhibition of its primary hydrolytic enzyme monoacylglycerol lipase (MAGL), will produce opioid sparing effects…
These findings, taken together, suggest that MAGL inhibition produces opiate sparing events with diminished tolerance, constipation, and cannabimemetic side effects.”
“The endocannabinoid system is implicated in the neurobiology of cocaine addiction, although it is not clear how cocaine regulates brain CB1 and CB2receptors, especially during adolescence, a critical moment for shaping adult response to drug use.
This study evaluated CB1 and CB2 protein levels in prefrontal cortex (PFC) and hippocampus (HC) by western blot analysis with specific and validated antibodies: (1) basally during adolescence (post-natal day PND 40, PND 47, PND 54), (2) by a sensitizing regimen of cocaine (15mg/kg, 7 d, i.p.) during different windows of adolescence vulnerability (PND 33-39, PND 40-46, PND 47-53), and (3) following repeated cocaine administration during adolescence (PND 33-39) in adulthood (PND 64).
The results demonstrated a dynamic and opposite basal modulation of CB1 and CB2 receptors in PFC and HC during adolescence. CB1 receptor levels were increased while CB2 receptors were decreased as compared to adulthood with asymptotes values around mid adolescence (PND 47) both in PFC (CB1: +45±22, p<0.05; CB2: -24±6%, p<0.05) and HC (CB1: +53±23, p<0.05; CB2: -20±8%, p<0.05).
Interestingly, cocaine only altered CB1(+55±10%, p<0.05) and CB2 (-25±10%, p<0.05) receptors when administered during early adolescence and only in PFC. However, the changes observed in PFC by repeated cocaine administration in adolescence were transient and did not endure into adulthood.
These results identified a period of vulnerability during adolescence at which cocaine dysregulated the content of CB receptors in PFC, suggesting an opposite role for these receptors in the effects mediated by cocaine.“
“The basolateral nucleus of the amygdala (BLA) is critical to the pathophysiology of anxiety-driven alcohol drinking and relapse.
The endogenouscannabinoid/type 1 cannabinoid receptor (eCB/CB1 ) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis.
Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats.
Here, we investigated the potential disruption of eCB/CB1signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol.
In the naïve rat BLA, the CB1agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity.
This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system.
In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms.
Notably, CB1 activation impaired ethanol’s facilitation of GABAergic transmission across both groups, but the AM251-induced and ethanol-induced facilitation of GABA release was additive, suggesting independent presynaptic sites of action.
Collectively, the present findings highlight a critical CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state.”
“The research of new therapeutic strategies for neuropathic pain represents a major current priority.
Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain.
One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system.
This system is highly expressed in neurons and immune cells, and it plays a crucial role in the development of neuropathic pain.
Preclinical studies have provided important findings, revealing the potential interest of the endocannabinoid system for the treatment of neuropathic pain.
These studies have reported the analgesic effects of cannabinoid agonists in multiple neuropathic pain models, and they have identified specific targets within this system to develop more effective and safe analgesic compounds.
Several clinical studies suggest that cannabinoids significantly reduced neuropathic pain…“
“Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation.
Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1receptors.”
“One of the most common psychological consequences of stroke is post-stroke depression (PSD). While more than 30 percent of stroke patients eventually develop PSD, the neurobiological mechanisms underlying such a phenomenon have not been well investigated.
Given the critical involvement of hypothalamic-pituitary-adrenal axis and endocannabinoid system in response to stressful stimuli, we evaluated the hypothesis that cannabinoid receptors in the hypothalamus are critical for modulation of post-stroke depression-like behaviors in rats.
Taken together, these results suggest that decreased CB1 receptor expression is likely associated with the development of post-stroke depression, and CB2 receptor may be a potential therapeutic target for the treatment post-stroke depressive disorders.”
“The cannabinoid receptor gene 1 (CNR1) encodes the human cannabinoid receptor CB1.
This receptor has a widespread distribution in the central nervous system (CNS), the main ligands being anandamide, 2-araquidonoil glycerol and marijuana constituents.
There is evidence to suggest an anti-neoplastic effect of these ligands in glial tissues mediated through stimulation of the receptor.
http://www.ncbi.nlm.nih.gov/pubmed/21156413
“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159
“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death.” http://www.ncbi.nlm.nih.gov/pubmed/15275820
“Cannabinoids, the active components of Cannabis sativa…” http://www.ncbi.nlm.nih.gov/pubmed/17952650
“Cannabinoid compounds are unique to cannabis and provide some interesting biological properties.
These compounds along with endocannabinoids, a group of neuromodulator compounds in the body especially in brain, express their effects by activation of G-protein-coupled cannabinoid receptors, CB1 and CB2.
There are several physiological properties attributed to the endocannabinoids including pain relief, enhancement of appetite, blood pressure lowering during shock, embryonic development, and blocking of working memory.
On the other hand, activation of endocannabinoid system may be suppresses evolution and progression of several types of cancer.
According to the results of recent studies, CB receptors are over-expressed in cancer cell lines and application of multiple cannabinoid or cannabis-derived compounds reduce tumor size through decrease of cell proliferation or induction of cell cycle arrest and apoptosis along with desirable effect on decrease of tumor-evoked pain.
Therefore, modulation of endocannabinoid system by inhibition of fatty acid amide hydrolase (FAAH), the enzyme, which metabolized endocannabinoids, or application of multiple cannabinoid or cannabis-derived compounds, may be appropriate for the treatment of several cancer subtypes. This review focuses on how cannabinoid affect different types of cancers.”
“The endocannabinoid system can modulate energy homeostasis by regulating feeding behaviour as well as peripheral energy storage and utilization.
Importantly, many of its metabolic actions are mediated through the cannabinoid type 1 receptor (CB1R), whose hyperactivation is associated with obesity and impaired metabolic function.
Herein, we explored the effects of administering rimonabant, a selective CB1R inverse agonist, upon key metabolic parameters in young (4 month old) and aged (17 month old) adult male C57BL/6 mice…
Collectively, our findings indicate a key role for CB1R in aging-related insulin resistance and metabolic dysfunction and highlight CB1R blockade as a potential strategy for combating metabolic disorders associated with aging.”