“Recent studies have indicated that type 2 cannabinoid receptor (CB2R) agonists reduce neurodegeneration after brain injury through anti-inflammatory activity.
The purpose of this study was to examine the time-dependent interaction of CB2R and inflammation in stroke brain.
In conclusion, our data support a time-dependent neuroprotection of CB2 agonist in an animal model of stroke.
Delayed post- treatment with PPAR-γ agonist induced behavioral recovery and microglial suppression; early treatment with CB2R agonist suppressed neurodegeneration in stroke animals.”
“The bone remodeling process is influenced by various factors, including estrogens and transmitters of the endocannabinoid system. In osteoblasts, cannabinoid receptors 2 (CB-2) are expressed at a much higher level compared to CB-1 receptors. Previous studies have shown that estrogens could influence CB-2 receptor expression.
In the present study, the possible interactions of a specific CB-2 agonist and a specific CB-2 antagonist/inverse agonist with 17-β-estradiol were investigated in primary human osteoblasts (HOB)…
In conclusion, for the first time a synergistic interaction between 17-β-estradiol and specific CB-2 antagonist/inverse agonist was observed in HOB.
Understanding the molecular pathways of this interaction would be of great importance in developing more efficient and safer drugs for treating or preventing bone diseases.”
“Synthetic cannabinoids (SCBs), also known under the brand names of “Spice,” “K2,” “herbal incense,” “Cloud 9,” “Mojo” and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors.
Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis.
This is likely due to SCBs being direct agonists of the cannabinoidreceptors, whereas THC is a partial agonist.
Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants.
The largest group of users is men in their 20s who participate in polydrug use.
The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use.
Treatment mostly involves symptom management and supportive care.
More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.”
“Cannabinoid CB1 receptors (CB1Rs) mediate the presynaptic effects of endocannabinoids in the central nervous system (CNS) and most behavioral effects of exogenous cannabinoids.
Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the CB1R C-terminus and can attenuate constitutive CB1R-mediated inhibition of Ca(2+) channel activity.
We now demonstrate cellular colocalization of CRIP1a at neuronal elements in the CNS and show that CRIP1a inhibits both constitutive and agonist-stimulated CB1R-mediated guanine nucleotide-binding regulatory protein (G-protein) activity.
These results confirm that CRIP1a inhibits constitutive CB1R activity and demonstrate that CRIP1a can also inhibit agonist-stimulated CB1R signaling and downregulation of CB1Rs. Thus, CRIP1a appears to act as a broad negative regulator of CB1R function.”
“Sustained administration of cannabinoid agonists acting on neuronal CB1 receptors (CB1Rs) are proposed for treating spasticity and chronic pain…
Our data suggest that CB1Rs may control the circuit gateway regulating the inflow of sensory afferent inputs into the locomotor circuits, indicating a potential site of action for restricting peripheral signals disruptive for locomotor activity.”
“Activation of cannabinoid receptor-2 (CB2) results in β-endorphin release from keratinocytes, which then acts on primary afferent neurons to inhibit nociception.
Our data also suggest that stimulation of MAPK contributes to the peripheral analgesic effect of CB2 receptor agonists.”
“The pharmacological (and recreational) effects of cannabis have been known for centuries. However, it is only recently that one has identified two subtypes of G-protein-coupled receptors, namely CB1 and CB2-receptors, which mediate the numerous effects of delta9-tetrahydrocannabinol and other cannabinoids.
Logically, the existence of cannabinoid-receptors implies that endogenous ligands for these receptors (endocannabinoids) exist and exert a physiological role. Hence, arachidonoylethanolamide (anandamide) and sn-2 arachidonoylglycerol, the first two endocannabinoids identified, are formed from plasma membrane phospholipids and act as CB1 and/or CB2 agonists.
The presence of both CB1 and CB2-receptors in the rat heart is noteworthy.
This endogenous cardiac cannabinoid system is involved in several phenomena associated with cardioprotective effects.
The reduction in infarct size following myocardial ischemia, observed in rats exposed to either LPS or heat stress 24 hours before, is abolished in the presence of a CB2-receptor antagonist.
Endocannabinoids and synthetic cannabinoids, the latter through either CB1 or CB2-receptors, exert direct cardioprotective effects in rat isolated hearts.
The ability of cannabinoids to reduce infarct size has been confirmed in vivo in anesthetized mice and rats. This latter effect appears to be mediated through CB2-receptors.
Thus, the endogenous cardiac cannabinoid system, through activation of CB2-receptors, appears to be an important mechanism of protection against myocardial ischemia.”
“Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, is a cannabinoid agonist that exerts its effects by activating at least two specific receptors (CB1 and CB2) that belong to the seven transmembrane G-protein coupled receptor (GPCR) family.
Both CB1 and CB2 mRNA and proteins are present in the heart.
THC treatment was beneficial against hypoxia in neonatal cardiomyocytes in vitro.
We also observed a neuroprotective effect of an ultra low dose of THC when applied to mice before brain insults.
The present study was aimed to test and characterize the cardioprotective effects of a very low dose of THC…
All protocols of THC administration were found to be beneficial.
CONCLUSION:
A single ultra low dose of THC before ischemia is a safe and effective treatment that reduces myocardial ischemic damage.”
“Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions…
The present study was designed to investigate the central (CB1) and the peripheral (CB2)cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia.
The antagonist for the CB2, but not CB1 receptor antagonist abolished the protective effect of THC.
In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors.
Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors.
L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection provided by THC.
Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production.
An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.”
