Cannabidiol and diabetic heart disease: Mechanistic evidence and translational challenges
Afolake Arowolo 1 , Oluyomi Adeyemi 2 , Toluwalope Ajonijebu 3 , Aminu Musa 4 , Hygon Mutavhatsindi 5 , Rabia Johnson 6 , Kenechukwu Obikeze 7
- 1Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Cape Town, Western Cape, South Africa; Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa. Electronic address: Afolake.Arowolo@mrc.ac.za.
- 2Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria.
- 3Department of Biochemistry, North-West University, Potchefstroom, North-West, South Africa.
- 4Department of Physiology, Nelson Mandela University, Gqeberha, Eastern Cape, South Africa.
- 5Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Cape Town, Western Cape, South Africa; Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa.
- 6Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Cape Town, Western Cape, South Africa.
- 7Department of Pharmacology, University of the Western Cape, Cape Town, Western Cape, South Africa.
Affiliationer
Abstract
Diabetic heart disease (DHD) is a major contributor to global cardiovascular morbidity, driven by a complex interplay of metabolic, inflammatory, oxidative, and fibrotic mechanisms. These interconnected pathways are not fully addressed by current cardiometabolic therapies, highlighting the need for novel multi-target interventions. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential modulator of several key processes implicated in DHD pathogenesis. Preclinical evidence demonstrates that CBD attenuates oxidative stress by reducing reactive oxygen species (ROS) production, suppresses nuclear factor-κB (NF-κB)-mediated inflammatory signaling, preserves endothelial function by improving nitric oxide (NO) bioavailability, and inhibits transforming growth factor-β (TGF-β)-driven fibrotic remodeling. These effects have been observed across in vitro and in vivo models of diabetic cardiomyopathy, where CBD improves both myocardial and vascular function. Mechanistically, CBD exerts its actions through negative allosteric modulation of CB₁ receptors and interaction with non-cannabinoid targets, including transient receptor potential vanilloid 1 (TRPV1), peroxisome proliferator-activated receptor gamma (PPARγ), and G protein-coupled receptor 55 (GPR55). Despite this robust preclinical foundation, clinical evidence supporting the efficacy of CBD in DHD remains limited. Existing human studies are largely restricted to non-diabetic populations or short-term metabolic and hemodynamic outcomes, and do not address disease-specific cardiac endpoints. Furthermore, translational challenges, including variability in dosing, product standardization, and potential drug-drug interactions, remain significant barriers to clinical implementation. Collectively, CBD represents a promising investigational candidate with multi-target potential to modulate the core pathophysiology of DHD. However, well-designed, disease-specific clinical trials are required to establish its therapeutic relevance and safety in diabetic populations.
Keywords: Cannabidiol; Cannabidiol (CBD); Cardiac fibrosis; Diabetic cardiomyopathy; Diabetic heart disease; Endocannabinoid system; Inflammation; Oxidative stress.
Copyright © 2026 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
