“Stimulation of cannabinoid type 1 (CB1) receptor in the rostral ventrolateral medulla (RVLM) increases renal sympathetic nerve activity (RSNA) and blood pressure (BP) in rats.
Thus, we hypothesized that abnormal expression of CB1 receptor in the RVLM may play a critical role in the pathogenesis of essential hypertension.
Taken together, our results suggested that alterations of CB1 receptor desensitization in the RVLM may play a role in the pathogenesis of essential hypertension.”
“We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone.
CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity.
Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue.
CNR1 is upregulated in states of type 2 diabetes and insulin resistance.
Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis.
Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.”
“The irritant properties of all smoke will naturally tend to promote a pro-inflammatory immune response with the corresponding production of potentially carcinogenic free radicals. However, cannabis promotes immune deviation to an anti-inflammatory Th2 response via immune-system specific CB2 receptors. Thus, the natural pharmacological properties of marijuana’s cannabinoids, that are not present in tobacco smoke, would minimize potential irritant initiated carcinogenesis. In contrast, the pharmacological activities of tobacco smoke would tend to amplify its carcinogenic potential by inhibiting the death of genetically damaged cells. Together these observations support the epidemiological study of the Kaiser Foundation that did not find cannabis smoking to be associated with cancer incidence. Additionally, the demonstrated cancer killing activities of cannabinoids has been ignored. Cannabinoids have been shown to kill some leukemia and lymphoma, breast and prostate, pheochromocytoma, glioma and skin cancer cells in cell culture and in animals.” http://www.bmj.com/rapid-response/2011/10/29/science-based-evaluation-cannabis-and-cancer
“Researchers at UT Southwestern Medical Center report the most detailed 3-D structure to date of the brain receptor that binds and responds to the chemical at the root of marijuana’s high.
Their high-resolution structure of the human cannabinoid receptor 1 (CB1) and its binding site for the chemical tetrahydrocannabinol (THC) should lead to a better understanding of how marijuana affects the brain.
The research also could aid discovery of new treatments for conditions that target the receptor, said Dr. Daniel Rosenbaum, Assistant Professor of Biophysics and Biochemistry at UT Southwestern.”
https://www.sciencedaily.com/releases/2016/11/161116131935.htm
“The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG), as well as the widely consumed plant (phyto)cannabinoid Δ9-tetrahydrocannabinol (THC)1. The cannabinoid receptors have been the targets of intensive drug discovery efforts owing to the therapeutic potential of modulators for controlling pain2, epilepsy3, obesity4, and other maladies. Although much progress has recently been made in understanding the biophysical properties of GPCRs, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. We used GPCR engineering and lipidic cubic phase (LCP) crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6 Å resolution. The extracellular surface of CB1, including the highly conserved membrane-proximal amino-terminal (N-terminal) region, is distinct from other lipid-activated GPCRs and forms a critical part of the ligand binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function, and will aid the design and optimization of cannabinoid system modulators for therapeutic ends.”
“Cannabinoid receptor type-2 (CB2, CB2 Receptor, or CB2-R) mediates analgesia, via two mechanisms. CB2 receptors contained in peripheral immune tissue mediates analgesia by altering cytokine profiles, and thus has little adverse effects on central nervous systems. CB2 is also expressed in the neurons and glial cells of the Central Nervous System (CNS). This neuronal expression may also contribute to pain attenuation. The CB2 receptor has been proposed as a potential target in treating chronic pain of several etiologies.”
“β-caryophyllene, which is a constituent of many essential oils, has been known to be a selective agonist of the cannabinoid receptor type-2 and to exert cannabimimetic anti-inflammatory effects in animals.
On the whole, this study demonstrates that the combination of β-caryophyllene, baicalin and (+)-catechin exerts synergistic suppressive effects on macrophages in vitro.
This composition may be a useful as an anti-inflammatory treatment strategy.”
“The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials.
Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor.
CB1 receptors appear to mediate anti-inflammatory effects of EA in a rat model of migraine.”
“The G protein-coupled cannabinoid receptors CB1, CB2, GPR18, and GPR55 regulate neurotransmission, pain, and inflammation and have been intensively investigated as potential drug targets. Each of these GPCRs is coupled to multiple effector proteins mediating divergent cellular signals. The ligand bias of cannabinoid-targeted compounds is only beginning to be quantified. Research into cannabinoid bias is now revealing correlations between bias in cell culture and functional outcomes in vivo. We present an example study of cannabinoid bias in the context of Huntington disease. In future, an understanding of cannabinoid receptor structure and quantification of ligand bias will optimize drug selection matched to patient population and disease.”
“Indole-based compounds, such as the alkyl-indole (AI) compound WIN55212-2, activate the cannabinoid receptors, CB1 and CB2, two well-characterized G protein-coupled receptors (GPCR). Reports indicate that several indole-based cannabinoid agonists, including WIN55212-2, lack selectivity and interact with at least two additional targets: AI-sensitive GPCRs and microtubules. Studying how indole-based compounds modulate the activity of these 4 targets has been difficult as selective chemical tools were not available. Here we report the pharmacological characterization of six newly-developed indole-based compounds (ST-11, ST-23, ST-25, ST-29, ST-47 and ST-48) that exhibit distinct binding affinities at AI-sensitive receptors, cannabinoid CB1 and CB2 receptors and the colchicine site of tubulin. Several compounds exhibit some level of selectivity for AI-sensitive receptors, including ST-11 that binds AI-sensitive receptors with a Kd of 52nM and appears to have a weaker affinity for the colchicine site of tubulin (Kd=3.2μM) and does not bind CB1/CB2 receptors. Leveraging these characteristics, we show that activation of AI-sensitive receptors with ST-11 inhibits both the basal and stimulated migration of the Delayed Brain Tumor (DBT) mouse glioma cell line. Our study describes a new series of indole-based compounds that enable the pharmacological and functional differentiation of alkylindole-sensitive receptors from cannabinoidreceptors and microtubules.”