“The relationship between cannabis use and diabetes is puzzling. Although cannabis users versus non-users should theoretically have a higher likelihood of diabetes, epidemiological studies suggest otherwise. However, previous epidemiological studies have not considered the potential confounding effects of mental health disorders. As such, the relationship between cannabis use and diabetes was examined while accounting for a range of potential confounders, including mental health disorders.
Category Archives: Diabetes
Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics.
“Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes without adverse neuropsychiatric effects.
We previously reported a human hCB1b isoform that is selectively enriched in pancreatic beta-cells and hepatocytes, providing a potential peripheral therapeutic hCB1R target. It is unknown whether there are peripherally enriched mouse and rat CB1R (mCB1 and rCB1, respectively) isoforms.
In this study, we found no evidence of peripherally enriched rodent CB1 isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1, intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced variant including all 6 exons.
Using RNAscope in situ hybridization, we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in GABAergic neurons in the hippocampus and cortex. RT-qPCR reveals that mCB1A and mCB1B are enriched in the brain, while mCB1B is not expressed in the pancreas or the liver. Rat rCB1R isoforms are differentially expressed in primary cultured neurons, astrocytes, and microglia.
We also investigated modulation of Cnr1 expression by insulin in vivo and carried out in silico modeling of CB1R with JD5037, a peripherally restricted CB1R inverse agonist, using the published crystal structure of hCB1R.
The results provide models for future CB1R peripheral targeting.”
Sub-chronic treatment with cannabidiol but not with URB597 induced a mild antidepressant-like effect in diabetic rats.
“Depression associated with diabetes has been described as a highly debilitating comorbidity. Due to its complex and multifactorial mechanisms, the treatment of depression associated with diabetes represents a clinical challenge.
Cannabidiol (CBD), the non-psychotomimetic compound derived from Cannabis sativa, has been pointed out as a promising compound for the treatment of several psychiatric disorders.
Here, we evaluated the potential antidepressant-like effect of acute or sub-chronic treatment with CBD in diabetic rats using the modified forced swimming test (mFST).
Also, to better understand the functionality of the endocannabinoid system in diabetic animals we also evaluated the effect of URB597, a fatty acid amide hydrolase inhibitor.
Acute treatment with either CBD or URB induced an antidepressant-like effect in NGL rats, but not in DBT rats. However, sub-chronic treatment with CBD (only at a dose of 30 mg/kg), but not with URB597, induced a mild antidepressant-like effect in DBT animals. Neither body weight nor blood glucose levels were altered by treatments.
Considering the importance of the endocannabinoid system to the mechanism of action of many antidepressant drugs, the mild antidepressant-like effect of the sub-chronic treatment with CBD, but not with URB597 does not invalidate the importance of deepening the studies involving the endocannabinoid system particularly in DBT animals.”
https://www.ncbi.nlm.nih.gov/pubmed/29885450
“The pharmacological importance of cannabidiol (CBD) has been in study for several years.
CBD is the major nonpsychoactive constituent of plant 
“Patients with obesity are susceptible to hypertension and diabetes. Over-activation of 
“Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans.
Obesity is associated with up-regulation of the endocannabinoid system, and blocking the 
“The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena.
In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving.
Moreover,