“Hemopressin, so-called because of its hypotensive effect, belongs to the derivatives of the hemoglobin α-chain. It was isolated from rat brain membrane homogenate by the use of catalytically inactive forms of endopeptidase 24.15 and neurolysin. Hemopressin has antihyperalgesic features that cannot be prevented by the opioid receptor antagonist, naloxone.
Here, we further confirm that hemopressins can modulate CB1 receptors and can have a slight modulatory effect on the opioid system.”
“The present study investigated the type 1 cannabinoid receptor (CB1R) as a potential candidate to mediate the homeostatic responses triggered by 24 hours of water deprivation (WD), which constitutes primarily a hydroelectrolytic challenge and also significantly impacts energy homeostasis.
The present results demonstrated for the first time that CB1R mRNA expression is increased in the hypothalamus of WD rats. Furthermore, the administration of ACEA, a CB1R selective agonist, potentiated WD-induced dipsogenic effect, whereas AM251, a CB1R antagonist, attenuated not only water but also salt intake in response to WD. In parallel with the modulation of thirst and salt appetite, we confirmed that CB1Rs are essential for the development of appropriated neuroendocrine responses…
In conclusion, the present study demonstrated that CB1Rs participate in the homeostatic responses regulating fluid balance and energy homeostasis during WD.”
“Variations in environmental aversiveness influence emotional memory processes in rats. We have previously shown that cannabinoid effects on memory are dependent on the stress level at the time of training as well as on the aversiveness of the environmental context. Here, we investigated whether the hippocampal endocannabinoid system modulates memory retrieval depending on the training-associated arousal level…
The present findings indicate that the endocannabinoid 2-AG in the hippocampus plays a key role in the selective regulation of spatial memory retrieval of stressful experience, shedding light on the neurobiological mechanisms involved in the impact of stress effects on memory processing.
Endogenous cannabinoids play a central role in the modulation of memory for emotional events. Here we demonstrate that the endocannabinoid 2-arachidonoylglycerol in the hippocampus, a brain region crucially involved in the regulation of memory processes, selectively modulates spatial memory recall of stressful experiences. Thus, our findings provide evidence that the endocannabinoid 2-arachidonoylglycerol is a key player in mediating the impact of stress on memory retrieval.
These findings can pave the way to new potential therapeutic intervention for the treatment of neuropsychiatric disorders, such as post-traumatic stress disorder, where a previous exposure to traumatic events could alter the response to traumatic memory recall leading to mental illness.”
“Macrophages are pivotal effector cells in immune responses and tissue remodeling by producing a wide spectrum of mediators, including angiogenic and lymphangiogenic factors.
Activation of cannabinoid receptor types 1 and 2 has been suggested as a new strategy to modulate angiogenesis in vitro and in vivo.
We investigated whether human lung-resident macrophages express a complete endocannabinoid system by assessing their production of endocannabinoids and expression of cannabinoid receptors…
Activation of cannabinoid receptors on tissue-resident macrophages might be a novel strategy to modulate macrophage-assisted vascular remodeling in cancer and chronic inflammation.”
“Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.” http://www.ncbi.nlm.nih.gov/pubmed/26459312
https://link.springer.com/article/10.1007%2Fs13277-015-4182-8
“Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research.
Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system.
This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others.
Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.”
“Chronic diseases are due to deviations of fundamental physiological systems, with different pathologies being characterised by similar malfunctioning biological networks.
The ensuing compensatory mechanisms may weaken the body’s dynamic ability to respond to further insults and reduce the efficacy of conventional single target treatments.
The multitarget, systemic, and prohomeostatic actions emerging for plant cannabinoids exemplify what might be needed for future medicines.
Indeed, two combined cannabis extracts were approved as a single medicine (Sativex®), while pure cannabidiol, a multitarget cannabinoid, is emerging as a treatment for paediatric drug-resistant epilepsy.
Using emerging cannabinoid medicines as an example, we revisit the concept of polypharmacology and describe a new empirical model, the ‘therapeutic handshake’, to predict efficacy/safety of compound combinations of either natural or synthetic origin.”
“This study aimed to address the questions of whether Δ(9)-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1 A receptors in vitro and (ii) induce any apparent 5-HT₁A receptor-mediated antipsychotic effects in vivo…
Our findings suggest that THCV can enhance 5-HT₁A receptor activation, and that some of its apparent antipsychotic effects may depend on this enhancement.
We conclude that THCV has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia.”
“Exercise is rewarding, and long-distance runners have described a runner’s high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia.
A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid).
Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running.
We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors.
We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner’s high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.”
http://www.ncbi.nlm.nih.gov/pubmed/26438875
“Activation of the endocannabinoid system through CB1, CB2 and additional receptor subtypes results in the inhibition of a broad range of cancers.
The endocannabinoid system was discovered through research focusing on the classical cannabinoid agonist, ?9-tetrahydrocannabinol (?9-THC), and other synthetic cannabinoids.
This proposal will focus on the potential treatment of human breast cancer using cannabinoids as selective antitumor agents.
We have found that cannabinoid compounds activating CB1, CB2 and additional receptor subtypes can inhibit breast cancer cell proliferation and invasiveness and we have discovered down-stream targets that potentially link cannabinoid receptor stimulation to these effects.
Furthermore, our preliminary studies provide evidence that endogenous endocannabinoid tone tonically inhibits metastatic breast cancer cell proliferation and invasiveness through the activation of cannabinoid receptors.
Our preliminary data also suggests that cannabinoid compounds possess selective efficacy, having less adverse effects on the normal human cells from which the breast cancers arise.
Since toxicity in healthy tissue limits the efficacy of current cancer treatments, discovering the mechanism behind selective efficacy in human tissues is of clinical importance.
Cannabinoids can inhibit multiple types of tumor growth in vivo…
Testing the hypotheses outlined in the application may lead to the development of effective inhibitors of breast, and perhaps other, cancers.
This research may also elucidate novel mechanisms related to the anticancer activity of cannabinoids, and will serve to develop the career of the candidate in the field of cancer biology.”