“While activation of cannabinoid (CB2) receptors has been shown to be neuroprotective, no studies have examined whether this neuroprotection is directed at cerebral arterioles and no studies have examined whether activation of CB2 receptors can rescue cerebrovascular dysfunction during a chronic disease state such as type 1 diabetes (T1D).
Our goal was to test the hypothesis that administration of a CB2 agonist (JWH-133) would improve impaired endothelial (eNOS)- and neuronal (nNOS)- dependent dilation of cerebral arterioles during T1D.
In vivo diameter of cerebral arterioles in nondiabetic and T1D rats was measured in response to an eNOS-dependent agonist (adenosine 5′-diphosphate; ADP), an nNOS-dependent agonist (N-methyl-D-aspartate; NMDA), and an NOS-independent agonist (nitroglycerin) before and 1 hour following JWH-133 (1 mg/kg IP). Dilation of cerebral arterioles to ADP and NMDA was greater in nondiabetic than in T1D rats.
Treatment with JWH-133 increased responses of cerebral arterioles to ADP and NMDA in both nondiabetic and T1D rats. Responses of cerebral arterioles to nitroglycerin were similar between nondiabetic and T1D rats, and JWH-133 did not influence responses to nitroglycerin in either group. The restoration in responses to the agonists by JWH-133 could be inhibited by treatment with a specific inhibitor of CB2 receptors (AM-630; 3 mg/kg IP).
Thus, activation of CB2 receptors can potentiate reactivity of cerebral arterioles during physiologic and pathophysiologic states. We speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular diseases via a mechanism that can increase cerebral blood flow.”
https://pubmed.ncbi.nlm.nih.gov/32979391/
“Activation of CB2 receptors improves cerebral vascular function. Activation of CB2 receptors improves responses in type 1 diabetes. We speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular disease that can contribute to the pathogenesis of stroke.”
https://www.sciencedirect.com/science/article/pii/S0026286220301370?via%3Dihub
“Diabetes is a chronic disease associated with a high number of complications such as peripheral neuropathy, which causes sensorial disturbances and may lead to the development of diabetic neuropathic pain (DNP). The current treatment for DNP is just palliative and the drugs may cause severe adverse effects, leading to discontinuation of treatment. Thus, new therapeutic targets need to be urgently investigated.
“Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes.
“Genus Cannabis belong to family Cannabaceae and is traditionally used as medicinal plant against many diseases notably asthma, malaria, treatment of skin diseases, diabetes and headache. The plant Cannabis sativa L. is flowering and an annual herbaceous plant located to eastern Asia but now of cosmopolitan distribution due to extensive cultivation.
“The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality.
“The synthetic atypical cannabinoid Abn-CBD, a 
“Phytocannabinoids (pCBs) are a large family of meroterpenoids isolated from the plant Cannabis sativa. Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best investigated phytocannabinoids due to their relative abundance and interesting bioactivity profiles. In addition to various targets, THC and CBD are also well-known agonists of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor involved in energy homeostasis and lipid metabolism. In the search of new pCBs potentially acting as PPARγ agonists, we identified cannabimovone (CBM), a structurally unique abeo-menthane pCB, as a novel PPARγ modulator via a combined computational and experimental approach. The ability of CBM to act as dual PPARγ/α agonist was also evaluated. Computational studies suggested a different binding mode toward the two isoforms, with the compound able to recapitulate the pattern of H-bonds of a canonical agonist only in the case of PPARγ. Luciferase assays confirmed the computational results, showing a selective activation of PPARγ by CBM in the low micromolar range. CBM promoted the expression of PPARγ target genes regulating the adipocyte differentiation and prevented palmitate-induced insulin signaling impairment. Altogether, these results candidate CBM as a novel bioactive compound potentially useful for the treatment of insulin resistance-related disorders.”
“Cardiovascular complications are the major cause of mortality in diabetic patients. However, the molecular mechanisms underlying diabetes-associated arrhythmias are unclear.
“The cellular microenvironment plays a critical role in the maintenance of bone marrow-derived mesenchymal stem cells (BM-MSCs) and their subsequent cell lineage differentiation. Recent studies suggested that individuals with adipocyte-related metabolic disorders have altered function and adipogenic potential of adipose stem cell subpopulations, primarily BM-MSCs, increasing the risk of heart attack, stroke or diabetes.