“The endocannabinoid system (ECS) is abundantly expressed in the brain. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of endocannabinoids. In this review, we highlight the new advances in cannabinoid signaling, focusing on a key component of the ECS, the type-1cannabinoid receptor (CB 1). In recent years, the development of new imaging and molecular tools has demonstrated that this receptor can be distributed in many cell types (e.g., neuronal or glial cells) and intracellular compartments (e.g., mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB 1 receptors according to their specific localization (e.g., glutamatergic or GABAergic neurons). Moreover, this receptor is expressed in the periphery, where it can modulate periphery-brain connections. Finally, the better understanding of the CB 1 receptor structure led researchers to propose interesting and new allosteric modulators. Thus, the advances and the new directions of the CB 1 receptor field will provide new insights and better approaches to profit from its interesting therapeutic profile.”
Category Archives: Endocannabinoid System
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
Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts.
“Recently, it has also been demonstrated that the pleiotropic cannabinoid system is involved in both liver and pancreatic fibrosis. Furthermore, cannabinoids may play a pro- or anti-fibrogenic role depending on their interaction with CB1r or CB2r.
This raises the possibility that pharmacologic modulation of the endocannabinoid system could be a target to limit tissue damage in pathologic fibrosis.
It has been demonstrated that the endocannabinoid system is up-regulated in pathologic fibrosis and that modulation of the cannabinoid receptors might limit the progression of uncontrolled fibrogenesis.
Both CB1 and CB2 receptors were over-expressed in dcSSc fibroblasts compared with healthy controls.
Our preliminary findings suggest that cannabinoids are provided with an anti-fibrotic activity, thereby possibly representing a new class of agents targeting fibrosis diseases.”
http://rheumatology.oxfordjournals.org/content/48/9/1050.long
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.”
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
Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer.
“Breast cancer is the second leading cause of cancer deaths among women.
Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system.
Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood.
We observed that estrogen receptor-α negative (ERα-) breast cancer cells highly express epidermal growth factor receptor (EGFR) as well as insulin-like growth factor-I receptor (IGF-IR). We also observed IGF-IR upregulation in ERα+ breast cancer cells.
In addition, we found that higher CNR2 expression correlates with better recurrence free survival in ERα- and ERα+ breast cancer patients.
Our studies showed that CNR2 activation inhibited EGF and IGF-I-induced migration and invasion of ERα+ and ERα- breast cancer cells.
In conclusion, we show that CNR2 activation suppresses breast cancer through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes.”
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.”
Synthetic cannabinoid receptor agonists and antagonists: implication in CNS disorders.
“Since the discovery of the cannabinoid receptors, numerous studies associate the endocannabinoid system with several physiological and pathological processes including cancer, appetite, fertility, memory, neuropathic and inflammatory pain, obesity, and neurodegenerative diseases.
Over the last two decades, several researches have been dedicated extensively on the cannabinoid receptors ligands since the direct activation of cannabinoid receptors results in several beneficial effects, in the brain and in the periphery.
During past years, cannabinoid CB1 and CB2 receptor ligands from plants or lab were rapidly developed and then various new structures were reported to be cannabinoids.
The CB1 and CB2 receptor ligands offer several therapeutic opportunities for several CNS-related diseases.
Based on the scientific literature, this review provides an overview of CB1 and CB2 receptor synthetic ligands obtained from drug research and in particular those synthesized for therapeutic purposes and potential clinical applications for central nervous system disorders.”
Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.
“Cannabinoid receptor 2 (CB2), a G protein-coupled receptor (GPCR), is a promising target for the treatment of neuropathic pain, osteoporosis, immune system, cancer, and drug abuse.”