
“The cannabinoid receptor 2 (CB2R) has been considered as a potential therapeutic target to ameliorate the neuroinflammation and cognitive impairments of Alzheimer’s disease (AD). However, there has been little research on the diverse roles of CB2R in regulating different forms of cognitive abilities and underlying neuroinflammatory mechanisms. Thus, the focus of the present study was to investigate the effects of CB2R activation on cognitive abilities, activation and phenotype conversion of microglia, and dendrite complexity.
Results showed that CB2R activation normalized the cortex-dependent novel object recognition memory deficit in a novel object recognition test (P < 0.05) and CB2R activation was ineffective for hippocampus-dependent spatial cognitive dysfunction in the Morris water maze test (P > 0.05). Moreover, activation of CB2R did not affect the formation of plaque in either the cortex or hippocampus (P > 0.05). Interestingly, in the cortex but not in the hippocampus of APP/PS1 mice, there was decreased immunofluorescence intensity of Iba1, M1 to M2 microglial phenotype conversion, and restored dendritic complexity after a long treatment period of CB2R agonist (All P < 0.05).
Our results demonstrated that CB2R activation exerts a beneficial role in novel object recognition ability concomitant with region-specific regulation in microglia-mediated neuroinflammation and dendritic complexity in AD-model mice.”
https://www.ncbi.nlm.nih.gov/pubmed/31150731
https://www.sciencedirect.com/science/article/pii/S0304394019303581?via%3Dihub
“Currently, the involvement of the endocannabinoid system in cancer development and possible options for a cancer-regressive effect of
“Obesity is characterized by chronic low-grade inflammation that contributes to development of cardiometabolic disorders.
“The acute toxicity of organophosphorus-based compounds is primarily a result of acetylcholinesterase inhibition in the central and peripheral nervous systems. The resulting cholinergic crisis manifests as seizure, paralysis, respiratory failure and neurotoxicity. Though overstimulation of muscarinic receptors is the mechanistic basis of central organophosphorus (OP) toxicities, short-term changes in synapse physiology that precede OP-induced seizures have not been investigated in detail. To study acute effects of OP exposure on synaptic function, field excitatory postsynaptic potentials (fEPSPs) were recorded from Schaffer collateral synapses in the mouse hippocampus CA1 stratum radiatum during perfusion with various OP compounds. Administration of the OPs paraoxon, soman or VX rapidly and stably depressed fEPSPs via a presynaptic mechanism, while the non-OP proconvulsant tetramethylenedisulfotetramine had no effect on fEPSP amplitudes. OP-induced presynaptic long-term depression manifested prior to interictal spiking, occurred independent of recurrent firing, and did not require NMDA receptor currents, suggesting that it was not mediated by activity-dependent calcium uptake. Pharmacological dissection revealed that the presynaptic endocannabinoid type 1 receptor (CB1R) as well as postsynaptic M1 and M3 muscarinic acetylcholine receptors were necessary for OP-LTD. Administration of CB1R antagonists significantly reduced survival in mice after a soman challenge, revealing an acute protective role for endogenous CB1R signaling during OP exposure. Collectively these data demonstrate that the endocannabinoid system alters glutamatergic synaptic function during the acute response to OP acetylcholinesterase inhibitors.”
“Cannabis and synthetic 

“Increases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6 months or longer after the patient’s last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited effectiveness. Therefore, the development of novel treatment strategies is an important preclinical research focus and an urgent need for patients. Approaches to prevent CIPN have yielded disappointing results since these compounds may interfere with the anti-tumor properties of chemotherapeutic agents. Nevertheless, the first (serotonin noradrenaline reuptake inhibitors [SNRIs], anticonvulsants, tricyclic antidepressants) and second (5% lidocaine patches, 8% capsaicin patches and weak opioids such as tramadol) lines of treatment for CIPN have shown some efficacy. The clinical challenge of CIPN management in cancer patients and the need to target novel therapies with long-term efficacy in alleviating CIPN are an ongoing focus of research. The endogenous
“Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.”