Anti-inflammatory potential of delta-9-tetrahydrocannabinol in hyperinsulinemia: an experimental study

Posted on October 14, 2022 by David

“Background: Hyperinsulinemia (HI) means that the amount of insulin in the blood is higher than normal and is often associated with type 2 diabetes. It is known that delta-9-tetrahydrocannabinol (THC) obtained from a medicinal plant, Cannabis sativa, has therapeutic effects on many diseases.

Objective: This study aimed to investigate the effects of THC on inflammatory and oxidant status in rat pancreas with HI.

Methods: Rats were divided into groups; Control, HI, THC and HI + THC. Each group consists of 8 animals. HI and HI + THC groups were given 10% fructose in the drinking water for 12 weeks. In the last four weeks of the experiment, 1.5 mg kg^-1 THC was injected intraperitoneally daily into THC and HI + THC groups. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) were detected. JNK/SAPK and Grap2/p38 levels, total antioxidant and oxidant capacities (TAC and TOC) were analyzed in the pancreas.

Results: Levels of IL-6, NF-κβ, and TNF-α mRNA expression were higher in the pancreas with HI than in the control (p < 0.001 for all). THC treatment reduced the expression of IL-6, NF-κβ, and TNF-α mRNAs in the HI + THC group compared to the HI group (p < 0.001 for all). TOC increased in the HI group compared to the control group (p < 0.001). However, THC treatment reduced TOC levels in the HI + THC group compared to the HI group (p < 0.001).

Conclusion: According to the results, the THC treatment may regulate inflammation and TOC in rats with hyperinsulinemia. Thus, we can say that THC may have anti-inflammatory and antioxidant potential in metabolic disorders.”

https://pubmed.ncbi.nlm.nih.gov/36239881/

https://link.springer.com/article/10.1007/s11033-022-07996-9

Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in gastroparesis: A sex- and subtype-dependent observation

Posted on August 24, 2022 by David

“Background: Gastroparesis (GP) is a motility disorder of the stomach presenting with upper gastrointestinal symptoms in the setting of delayed gastric emptying. Endocannabinoids are involved in the regulation of GI function including motility. However, their role in the pathophysiology of GP has not been sufficiently investigated. Our goal was to compare the circulating levels of endocannabinoids and cannabimimetic fatty acid derivatives in GP versus control subjects.

Methods: The study compared plasma concentrations of endocannabinoids and their lipoamine and 2-acyl glycerol congeners, measured by high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS-MS), in adult patients with diabetic gastroparesis (DM-GP; n = 24; n = 16 female), idiopathic gastroparesis (ID-GP; n = 19; n = 11 female), diabetic patients without GP (DM; n = 19; n = 10 female), and healthy controls (HC; n = 18; n = 10 female). Data, presented as mean ± SEM, were analyzed with ANOVA (Sidak post hoc).

Key results: Endocannabinoids anandamide (AEA: 0.5 ± 0.1 nMol/L) and 2-arachidonoyl glycerol (2-AG: 2.6 ± 0.7 nMol/L) were significantly lower in female DM-GP patients vs. DM females (AEA: 2.5 ± 0.7 nMol/L and 2-AG: 9.4 ± 3.3 nMol/L). Other monoacylglycerols including 2-palmitoyl glycerol and 2-oleoyl glycerol were also lower in female DM-GP patients compared to DM females. No changes were observed in men.

Conclusions & inferences: Endocannabinoids and other fatty acid derivatives with cannabimimetic properties are reduced in female DM-GP patients. Since GP, particularly with diabetic etiology, is more prevalent among women and since cannabinoids are antiemetic, this decrease in levels may contribute to symptom development in these subjects. Targeting the endocannabinoid system may be a future therapeutic option in DM-GP patients.”

https://pubmed.ncbi.nlm.nih.gov/32779297/

“Targeting the endocannabinoid system may be a future therapeutic option in DM-GP patients.”

https://onlinelibrary.wiley.com/doi/full/10.1111/nmo.13961

The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders

Posted on July 26, 2022 by David

“Rapidly increasing worldwide prevalence of obesity and related pathologies encompassing coronary heart disease, hypertension, metabolic syndrome, or type 2 diabetes constitute serious threats to global health and are associated with a significantly elevated risk of premature death. Considering the enormous burden of these pathologies, novel therapeutic and preventive patterns are indispensable.

Dysregulation of one of the most complex biological systems in the human body namely, the endocannabinoid system (ECS) may result in metabolic imbalance and development of insulin resistance, type 2 diabetes, or non-alcoholic fatty liver disease. Furthermore, many studies showed that physical exercises, depending on their type, intensity, and frequency, exert various alterations within the ECS.

Emerging evidence suggests that targeting the ECS via physical activity may produce robust beneficial effects on the course of metabolic pathologies. However, the data showing a direct correlation between the ECS and physical activity in the aspect of metabolic health are very scarce. Therefore, the aim of this review was to provide the most up-to-date state of knowledge about the interplay between the ECS activity and physical exercises in the novel therapeutic and preventive approach toward metabolic pathologies.

We believe that this paper, at least in part, will fulfill the existing gap in knowledge and encourage researchers to further explore this very complex yet interesting link between the ECS, its action in physical activity, and subsequent positive outcomes for metabolic health.”

https://pubmed.ncbi.nlm.nih.gov/35328503/

“To the best of our knowledge, this is the first review directly and comprehensively discussing the uncharted link between physical activity and its influence on the endocannabinoid signaling in the aspect of beneficial effects in the management of metabolic disorders. Considering the very alarming worldwide prevalence of these diseases as well as the unexplored potential of the topic, we believe that this paper, at least in part, will encourage researchers toward investigating this interesting, yet very complicated interplay. ECS and physical activity constitute robust and valuable therapeutic and preventive approaches that may significantly contribute to the decreased socioeconomic burden and the reduced annual number of patients suffering from obesity and other metabolic disorders. The future investigation should primarily encompass further discovery of the link between physical activity, alterations within endocannabinoid signaling and subsequently improved metabolic status of overweight, obese, and diabetic individuals.”

https://www.mdpi.com/1422-0067/23/6/3083/htm

“Exercise activates the endocannabinoid system”

https://pubmed.ncbi.nlm.nih.gov/14625449/

α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabis sativa

Posted on July 20, 2022 by David

“Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts.

Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of -7.5 and -6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in vitro assay on α-glucosidase revealed that THC and CBD exhibited good inhibitory activity, with the IC₅₀ values of 3.0 ± 0.37 and 5.5 ± 0.28 μg/ml, respectively.

These were better than the standard drug, acarbose (IC₅₀ of 488.6 ± 10.23 μg/ml).

Furthermore, two standardized cannabinoid extracts, SCE-I (C. sativa leaf extract) and SCE-II (C. sativa inflorescence extract) exhibited stronger inhibitory activity than THC and CBD, with the IC₅₀ values of 1.2 ± 0.62 and 0.16 ± 0.01 μg/ml, respectively.

The present study provides the first evidence that the standardized cannabinoid extracts containing THC and CBD have greater potential than CBD and THC in application as an α-glucosidase inhibitor.”

https://pubmed.ncbi.nlm.nih.gov/35856057/

https://www.sciencedirect.com/science/article/pii/S2665927122001046?via%3Dihub

Vascular responses disrupted by fructose-induced hyperinsulinemia improved with delta-9- tetrahydrocannabinol

Posted on June 29, 2022 by David

“Objectives: In recent years, cannabinoids have been shown to have beneficial effects on diabetic vascular complications.

Vascular complications due to fructose-induced hyperinsulinemia (HI) and diabetic vascular complications have similar mechanisms.

The aim of this experimental study was to observe whether the cannabinoid agonist delta-9-tetrahydrocannabinol (THC) has an ameliorating effect on fructose-induced HI and vascular responses in the aortic ringof rats with HI.

Methods: A total of 24 rats were categorized into 4 groups: control (standard food pellets and water), HI (water containing 10% fructose provided for 12 weeks), THC (1.5 mg/kg/day intraperitoneal administration for 4 weeks), and THC+HI.Body weight was measured again on the last day of the study and the serum insulin level was measured with an enzyme-linked immunosorbent assay. The acetylcholine (ACh) maximum relaxant effect in aortic rings pre-contractedwith noradrenaline (NA) was evaluated.

Results: The body weight of THC and THC+HI groups was lower compared with that of the controls (p<0.01). Increasedinsulin level as a result of fructose consumption decreased with THC administration (p<0.01) while the glucose level increased in all other groups compared with the control group (p<0.01, p<0.05). The NA Emax value decreased in thegroup receiving THC treatment (p<0.01). The increased ACh pD2 value in the HI groups also decreased in the THCtreatment group (p<0.0001). The decreased maximum inhibition value in the HI group increased significantly with THC administration (p<0.001).

Conclusion: THC demonstrated beneficial effects on fructose-induced HI. THC improved ACh-induced endothelialdependent relaxation in HI rat aortic rings.”

http://acikerisim.demiroglu.bilim.edu.tr:8080/xmlui/handle/11446/4516

https://internationalbiochemistry.com/jvi.aspx?un=IJMB-83703&volume=

Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy

Posted on June 7, 2022 by David

“Diabetic complications, chiefly seen in long-term situations, are persistently deleterious to a large extent, requiring multi-factorial risk reduction strategies beyond glycemic control. Diabetic cardiomyopathy is one of the most common deleterious diabetic complications, being the leading cause of mortality among diabetic patients. The mechanisms of diabetic cardiomyopathy are multi-factorial, involving increased oxidative stress, accumulation of advanced glycation end products (AGEs), activation of various pro-inflammatory and cell death signaling pathways, and changes in the composition of extracellular matrix with enhanced cardiac fibrosis. The novel lipid signaling system, the endocannabinoid system, has been implicated in the pathogenesis of diabetes and its complications through its two main receptors: Cannabinoid receptor type 1 and cannabinoid receptor type 2, alongside other components. However, the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated. This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy. These mechanisms include oxidative/ nitrative stress, inflammation, accumulation of AGEs, cardiac remodeling, and autophagy. A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.”

https://pubmed.ncbi.nlm.nih.gov/35664549/

“Diabetes-induced cardiomyopathy is a deleterious complication of the cardiovascular system characterized by structural and functional changes in the myocardium that ultimately lead to cardiac failure. The mechanisms underlying the development of diabetic cardiomyopathy are complex and involve several pathogenic pathways. A great body of evidence supported a special role of oxidative/nitrative stress and inflammation in the pathogenesis of diabetic cardiomyopathy. The endocannabinoid system has been implicated in the development of several pathological conditions including cardiovascular disorders. Several mechanisms have been proposed as targets by which cannabinoids and the endocannabinoid system could modulate cardiovascular disorders and recent evidence suggested the involvement of this system in the pathogenesis of diabetic cardiomyopathy. Indeed, the manipulation of the endocannabinoid system could represent a promising therapeutic approach for diabetic cardiomyopathy, and several mechanisms have been proposed for this role including its effects on oxidative/nitrative stress, inflammatory pathways, and autophagy together with possible effects on cardiac remodeling. However, more research is needed to define the exact mechanisms of the intervention of the different components of this system in diabetic cardiomyopathy.”

https://www.wjgnet.com/1948-9358/full/v13/i5/387.htm

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Posted on September 10, 2021 by David

“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Cannabidiol – A phytocannabinoid that widely affects sphingolipid metabolism under conditions of brain insulin resistance

Posted on August 27, 2021 by David

Biomedicine & Pharmacotherapy “Obesity-related insulin resistance (IR) and attenuated brain insulin signaling are significant risk factors for neurodegenerative disorders, e.g., Alzheimer’s disease. IR and type 2 diabetes correlate with an increased concentration of sphingolipids, a class of lipids that play an essential structural role in cellular membranes and cell signaling pathways.

Cannabidiol (CBD) is a nonpsychoactive constituent of Cannabis sativa plant that interacts with the endocannabinoidome. Despite known positive effects of CBD on improvement in diabetes and its aftermath, e.g., anti-inflammatory and anti-oxidant effects, there are no studies evaluating the effect of phytocannabinoids on the brain insulin resistance and sphingolipid metabolism. Our experiment was carried out on Wistar rats that received a high-fat diet and/or intraperitoneal CBD injections.

In our study, we indicated inhibition of de novo synthesis and salvage pathways, which resulted in significant changes in the concentration of sphingolipids, e.g., ceramide and sphingomyelin. Furthermore, we observed reduced brain IR and decreased tau protein phosphorylation what might be protective against neuropathologies development.

We believe that our research will concern a new possible therapeutic approach with Cannabis -plant derived compounds and within a few years, cannabinoids would be considered as prominent substances for targeting both metabolic and neurodegenerative pathologies.”

https://pubmed.ncbi.nlm.nih.gov/34435590/

“CBD might be an essential factor that leads to the reduction of brain IR. Thus, we believe that our research will concern a new possible therapeutic approach with a Cannabis-plant derived compounds and within a few years, those substances would be considered as prominent compounds for targeting both metabolic and neurodegenerative pathologies.”

https://www.sciencedirect.com/science/article/pii/S0753332221008404?via%3Dihub

Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes

Posted on August 12, 2021 by David

“Δ9-Tetrahydrocannabivarin (THCV) is a cannabis-derived compound with unique properties that set it apart from the more common cannabinoids, such as Δ9-tetrahydrocannabinol (THC). The main advantage of THCV over THC is the lack of psychoactive effects. In rodent studies, THCV decreases appetite, increases satiety, and up-regulates energy metabolism, making it a clinically useful remedy for weight loss and management of obesity and type 2 diabetic patients. The distinctions between THCV and THC in terms of glycemic control, glucose metabolism, and energy regulation have been demonstrated in previous studies. Also, the effect of THCV on dyslipidemia and glycemic control in type 2 diabetics showed reduced fasting plasma glucose concentration when compared to a placebo group. In contrast, THC is indicated in individuals with cachexia. However, the uniquely diverse properties of THCV provide neuroprotection, appetite suppression, glycemic control, and reduced side effects, etc.; therefore, making it a potential priority candidate for the development of clinically useful therapies in the future. Hopefully, THCV could provide an optional platform for the treatment of life-threatening diseases.”

https://pubmed.ncbi.nlm.nih.gov/33526143/

“The psychoactive effects of THC in marijuana are the main reasons for its classification as a Schedule I substance, even though it is the THC that the U.S. Food and Drug Administration (FDA) approved for appetite stimulation and weight gain. In contrast to THC, clinical and therapeutic advantages of THCV regarding its lack of psychoactive effects in human studies are of great value in pharmacotherapy. It is envisioned that the unique and diverse characteristics of THCV could be explored for further development into clinically useful medicines for the treatment of life-threatening diseases.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-0016-7

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Posted on July 24, 2021 by David

“In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite.

The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB₁); cannabinoid receptor 2 (CB₂), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion.

The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers.

The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers.

In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.”

https://pubmed.ncbi.nlm.nih.gov/34205169/

https://www.mdpi.com/1420-3049/26/11/3389

www.thctotalhealthcare.com

Category Archives: Diabetes