“The cyclic AMP assay is a functional assay that is commonly used to determine the pharmacological behavior (agonists, antagonists, inverse agonists) of G-protein-coupled receptor (GPCR) ligands. Here, we describe the cyclic AMP assay that is carried out with commercially available non-radioligand ready-to-use kits and Chinese hamster ovarian (CHO) cells stably transfected with the human cannabinoid CB2 receptor.”
Tag Archives: agonists
Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.
:”The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.
CONCLUSION:
CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.”
Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.
“The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats.
In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment.
Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation.”
http://www.ncbi.nlm.nih.gov/pubmed/27230394
“The most dangerous drug in the world: ‘Devil’s Breath’ chemical from Colombia can block free will, wipe memory and even kill. Scopolamine often blown into faces of victims or added to drinks. Within minutes, victims are like ‘zombies’ – coherent, but with no free will. Drug is made from borrachero tree, which is common in Colombia” http://www.dailymail.co.uk/news/article-2143584/Scopolamine-Powerful-drug-growing-forests-Colombia-ELIMINATES-free-will.html
“Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.” http://www.ncbi.nlm.nih.gov/pubmed/27230394
The effect of cannabinoids on dinitrofluorobenzene-induced experimental asthma in mice.
“Cannabinoids have anti-inflammatory effects and can produce bronchodilation in the airways.
We have investigated the effects of cannabinoids on tracheal hyperreactivity and airway inflammation in dinitrofluorobenzene (DNFB)-induced experimental non-atopic asthma in mice.
These results show that cannabinoid CB1 receptor agonist can prevent tracheal hyperreactivity to 5-HT in DNFB-induced non-atopic asthma in mice.”
Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update.
“Modulation of the CB2 receptor is an interesting approach for pain and inflammation, arthritis, addictions, neuroprotection, and cancer, among other possible therapeutic applications, and is devoid of central side effects.
Structural diversity of CB2 modulator scaffolds characterized the patent literature.
Several CB2 agonists reached clinical Phase II for pain management and inflammation.
Other therapeutic applications need to be explored such as neuroprotection and/or neurodegeneration.”
Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages.
“Inflammatory response plays an important role in the activation and progress of many debilitating diseases. Natural products, like cannabidiol, a constituent of Cannabis sativa, and moringin, an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucomoringin present in Moringa oleifera seeds, are well known antioxidants also endowed with anti-inflammatory activity.
This is due to a covalent-based mechanism for ITC, while non-covalent interactions underlie the activity of CBD. Since these two mechanisms are distinct, and the molecular endpoints are potentially complementary, we investigated in a comparative way the protective effect of these compounds alone or in combination on lipopolysaccharide-stimulated murine macrophages.
Our results show that the cannabidiol (5μM) and moringin (5μM) combination outperformed the single constituents that, at this dosage had only a moderate efficacy on inflammatory (Tumor necrosis factor-α, Interleukin-10) and oxidative markers (inducible nitric oxide synthase, nuclear factor erythroid 2-related factor 2, nitrotyrosine). Significant upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3 was observed in cells treated with cannabidiol-moringin combination.
Treatment with the transient receptor potential vanilloid receptor 1 antagonist was detrimental for the efficacy of cannabidiol, while no effect was elicited by cannabinoid receptor 1 and cannabinoid receptor 2 antagonists. None of these receptors was involved in the activity of moringin.
Taken together, our in vitro results testify the anti-inflammatory, antioxidative, and anti-apoptotic effects of the combination of cannabidiol and moringin.”
Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease
“Brain disorders, including Alzheimer’s disease (AD), often involve specific early alterations in the metabolism of glucose in the brain.
The idea of alleviating symptoms of dementia by boosting cerebral energy metabolism has been toyed with for decades, yet safe pharmacological agents with well characterized mechanism of action are still lacking.
In this sense, we have investigated here the local cerebral glucoregulatory potential of the endocannabinoid system in rodents.
Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations.
Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents.
In conclusion, the present results provide the first direct pharmacological evidence in vitroand in vivo of a role of CB2R in central glucoregulation.
Additionally, we found that glucoregulation by endogenous CB2R signalling is negatively affected by β-amyloidosis, thought to be the first pathological step in AD.
Therefore, it would be interesting to perform further studies to define how CB2R mediated glucoregulation contributes to the recently discovered therapeutic potential of CB2R agonists in animal models of AD”
http://www.sciencedirect.com/science/article/pii/S0028390816300879
Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis
“Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive.
One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB2) is expressed primarily by immune cells.
Theoretically, selective CB2 agonists should be devoid of psychoactive effects.
In this study, we investigated therapeutic effects of a selective CB2 agonist on arthritis.
The present study suggests that a selective CB2 agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis.
This is the first report of therapeutic effect of a selective CB2 agonist on CIA.
Although the effect was mild, optimization of dosage and/or treatment protocol might enhance the effect.
Perhaps, more potent selective CB2agonists might solve this problem.
Cannabinoids are pharmacologically active components of Cannabis sativa.”
Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
“Breast cancer is the leading cause of cancer-related deaths among women aged 34–50 worldwide, and is the most commonly diagnosed metastasizing tumor in women of all ages. Despite advances in understanding breast cancer as a disease, there remains a critical need for novel disease-modifying therapeutics.
Nonspecific cannabinoids, cannabinoid receptor 2 (CB2)-selective, as well as cannabinoid receptor 1 (CB1)-selective compounds have yielded similar antitumor results in several tumor models. The lack of neuronal expression of CB2 receptors precludes CB2 selective compounds from inducing the psychotropic effects that typically accompany CB1 activation.
Our group and others have shown that CB2 agonists displaying selectivity for the CB2 receptor can decrease tumor cell viability and significantly attenuate cancer-induced bone pain without displaying psychoactive or addictive properties.
…antitumor effects of cannabinoids have been demonstrated in a variety of tumor models…
The antiproliferative effects of a CB2 agonist along with our previous work demonstrating significant efficacy in inhibiting bone cancer pain and slowing bone loss in a murine model of advanced breast cancer strongly suggest that CB2 agonists should be investigated in humans as adjunct therapy for advanced stages of breast cancer.
Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems.
The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.
Several groups have shown that both nonselective cannabinoid and CB2-specific compounds decrease breast cancer viability in vitro and in vivo: Δ9-tetrahydrocannabinol and CB2-selective agonist, JWH-133, have been demonstrated to exert considerable antitumoral effects…”
Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl.
“Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ9-THC) enhance some (antinociceptive) but not other (positive reinforcing) effects of mu opioid receptor agonists, suggesting that cannabinoids might be combined with opioids to treat pain without increasing, and possibly decreasing, abuse.
These data indicate that the discriminative stimulus effects of nalbuphine are more sensitive to attenuation by cannabinoids than those of fentanyl. That the discriminative stimulus effects of some opioids are more susceptible to modification by drugs from other classes has implications for developing maximally effective therapeutic drug mixtures with reduced abuse liability.”