The pharmacology and therapeutic role of cannabidiol in diabetes

In recent years, cannabidiol (CBD), a non-psychotropic cannabinoid, has garnered sub- stantial interest in drug development due to its broad pharmacological activity and multi-target effects. Diabetes is a chronic metabolic disease that can damage multiple organs in the body, leading to the development of complications such as abnor- mal kidney function, vision loss, neuropathy, and cardiovascular disease. CBD has demonstrated significant therapeutic potential in treating diabetes mellitus and its com- plications owing to its various pharmacological effects. This work summarizes the role of CBD in diabetes and its impact on complications such as cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy. Strategies for discovering molecular targets for CBD in the treatment of diabetes and its complications are also proposed. Moreover, ways to optimize the structure of CBD based on known targets to generate new CBD analogues are explored.

Tetrahydrocannabivarin (THCV) Protects Adipose-Derived Mesenchymal Stem Cells (ASC) against Endoplasmic Reticulum Stress Development and Reduces Inflammation during Adipogenesis

The endoplasmic reticulum (ER) fulfills essential duties in cell physiology, and impairment of this organelle’s functions is associated with a wide number of metabolic diseases. When ER stress is generated in the adipose tissue, it is observed that the metabolism and energy homeostasis of the adipocytes are altered, leading to obesity-associated metabolic disorders such as type 2 diabetes (T2D). In the present work, we aimed to evaluate the protective effects of ∆9-tetrahydrocannabivarin (THCV, a cannabinoid compound isolated from Cannabis sativa L.) against ER stress in adipose-derived mesenchymal stem cells. Our results show that pre-treatment with THCV prevents the subcellular alteration of cell components such as nuclei, F-actin, or mitochondria distribution, and restores cell migration, cell proliferation and colony-forming capacity upon ER stress. In addition, THCV partially reverts the effects that ER stress induces regarding the activation of apoptosis and the altered anti- and pro-inflammatory cytokine profile. This indicates the protective characteristics of this cannabinoid compound in the adipose tissue. Most importantly, our data demonstrate that THCV decreases the expression of genes involved in the unfolded protein response (UPR) pathway, which were upregulated upon induction of ER stress. Altogether, our study shows that the cannabinoid THCV is a promising compound that counters the harmful effects triggered by ER stress in the adipose tissue. This work paves the way for the development of new therapeutic means based on THCV and its regenerative properties to create a favorable environment for the development of healthy mature adipocyte tissue and to reduce the incidence and clinical outcome of metabolic diseases such as diabetes.

Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort)

Authors: Tangui Barré, Marie Libérée Nishimwe, Camelia Protopopescu, Fabienne Marcellin, Fabrice Carrat, Céline Dorival, Elisabeth Delarocque‐Astagneau, Dominique Larrey, Marc Bourlière, Ventzislava Petrov‐Sanchez, Mélanie Simony, Stanislas Pol, Hélène Fontaine, Patrizia Carrieri…

Phytocannabinoids: Useful Drugs for the Treatment of Obesity? Special Focus on Cannabidiol.

Authors: Patrycja Bielawie, Ewa Harasim-Symbor, Adrian Chabowski
Frontiers in Endocrinology, 4 March 2020

Currently, an increasing number of diseases related to insulin resistance and obesity is an alarming problem worldwide. It is well-known that the above states can lead to the development of type 2 diabetes, hypertension, and cardiovascular diseases. An excessive amount of tria…

The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities.

Authors: Dixon H. Xu, Benjamin D. Cullen, Meng Tang, Yujiang Fang
Current Pharmaceutical Biotechnology, December 2019

BACKGROUND: Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of ca…

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases.

Authors: Maura Argenziano, Chiara Tortora, Giulia Bellini, Alessandra Di Paola, Francesca Punzo, et al
International Journal of Molecular Sciences, 23 November 2019

Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the im…

Therapeutic potential of cannabinoid receptor 2 in the treatment of diabetes mellitus and its complications.

Authors: Vivek S. Kumawat, Ginpreet Kaur
European Journal of Pharmacology, 5 November 2019

The biological effects of endocannabinoid system are mediated by two types of receptors, cannabinoid 1 (CB1) and cannabinoid 2 receptor (CB2). They play a pivotal role in the management of pain, inflammation, cancer, obesity and diabetes mellitus. CB2 receptor activity downreg…

Cannabis: From a Plant That Modulates Feeding Behaviors toward Developing Selective Inhibitors of the Peripheral Endocannabinoid System for the Treatment of Obesity and Metabolic Syndrome.

Authors: Shira Hirsch, Joseph Tam
Toxins, 15 May 2019

In this review, we discuss the role of the endocannabinoid (eCB) system in regulating energy and metabolic homeostasis. Endocannabinoids, via activating the cannabinoid type-1 receptor (CB1R), are commonly known as mediators of the thrifty phenotype hypothesis due to their act…

Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications.

Authors: Arulkumar Nagappan, Jooyeon Shin, Myeong Ho Jung
International Journal of Molecular Sciences, 29 April 2019

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with…

Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.

Authors: Mark S. Wallace, Thomas D. Marcotte, Anya Umlauf, Ben Gouaux, Joseph H. Atkinson
The Journal of Pain, July 2015

A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis. In a crossover design, each participant was exposed to 4 single dos…

The impact of marijuana use on glucose, insulin, and insulin resistance among US adults.

Authors: Elizabeth A. Penner, Hannah Buettner, Murray A. Mittleman
The American Journal of Medicine, July 2013

BACKGROUND: There are limited data regarding the relationship between cannabinoids and metabolic processes. Epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users compared with people who have never used marijuana, suggestin…

Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III.

Authors: Tripathi B. Rajavashisth, Magda Shaheen, Keith C. Norris, Deyu Pan, et al
BMJ Open, 24 February 2012

OBJECTIVE: To determine the association between diabetes mellitus (DM) and marijuana use. DESIGN: Cross-sectional study. SETTING: Data from the National Health and Nutrition Examination Survey (NHANES III, 1988-1994) conducted by the National Center for Health Statistics of th…