Expanding Research on Cannabis-Based Medicines for Liver Steatosis: A Low-Risk High-Reward Way Out of the Present Deadlock?

Abstract

Obesity and nonalcoholic fatty liver disease (NAFLD) constitute global and growing epidemics that result in therapeutic dead ends. There is an urgent need for new and accessible treatments to improve and widen both preventive and curative approaches against NAFLD. The endocannabinoid system (ECS) is recognized as a complex signaling apparatus closely related to metabolic disorders and is a key target for treating NAFLD. Despite a lack of conclusive clinical trials, observational and pre-clinical studies highlight putative benefits of phytocannabinoids on liver steatosis through multiple pathways. Owing to both its safety profile and its diversity of active compounds acting primarily (although not exclusively) on the ECS—and its expanded version, the endocannabinoidome, the Cannabis plant should be considered a major prospect in the treatment of NAFLD. However, seizing this opportunity, and intensifying clinical research in this direction, will require overcoming both scientific and nonscientific barriers.

The Role of Cannabidiol in Liver Disease: A Systemic Review

“…Additionally, the endocannabinoid system is closely related to metabolic disorders, and phytocannabinoids are considered a promising avenue for treating MASLD [15]. Also, CBD derivatives have lowered low-density lipoprotein levels in high-fat diet (HFD) fed mice [16].…”

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders

“…Finally, the therapeutic targets of anabolic or catabolic endocannabinoid enzymes have been hampered by the extensiveness of this neural system and the correlated phytocannabinoid drugs, which interact with several neuromediators, such as endogenous opioid peptides and GABA, to form a broad alternative network of metabolic pathways and processes 10,53–55 . Therefore, just as the terms “transcriptome”, “proteome” and “metabolome” emerged, the term “endocannabinoidome” has been developed 54,56–59 …”

A literature review on the therapeutic applicability of cannabidiol in epilepsy, multiple sclerosis and Parkinson's disease

“…In this sense, the therapeutic targeting of anabolic or catabolic endocannabinoid enzymes has been hampered by the promiscuity of this system, which interacts with several neuromediators, such as endogenous opioids and GABA, forming a broad alternative network of metabolic pathways and processes [10,[35][36][37]. Therefore, just as the terms transcriptome, proteome and metabolome emerged, the term "endocannabinoidome" has been used [36,[38][39][40][41].…”