Cannabis, commonly known as marijuana, is used by at least 18% of the United States (US) population, which makes it the most commonly used federally illegal drug in the United States. It is widely used for recreational purposes, while its therapeutic benefits have been extensively explored in the US. For several years, cannabis has been used for the treatment of diverse health conditions, including pain management, anti-inflammatory effects, and spasticity associated with multiple sclerosis and other neurodegenerative diseases. However, cannabis use has been associated with some acute and chronic adverse effects. This review sheds light on gastrointestinal disorders, gastroesophageal reflux disease, pancreatitis, and peptic ulcer disease that have been associated with cannabis use.

Diabetic peripheral neuropathy (DPN) is characterized by progressive loss of peripheral nerves, which causes numbness, weakness, and severe pain. The medications available currently provide only modest relief from the pain of DPN and are associated with various side effects, which has generated an enormous demand for research on new therapeutic approaches. Dysregulation of the endocannabinoid system has been reported in DPN. Cannabinoid-based medications have gained increasing attention as a potential therapy to alleviate DPN pain. Endocannabinoids and cannabinoids\' actions are mediated primarily by cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R). Cannabinoids that activate CB1R have demonstrated a profound antinociceptive effect, although CB1R is associated with undesirable psychoactive effects. Peripherally restricted CB1R agonists help overcome this problem; however, adverse metabolic and cardiovascular effects limit its therapeutic use. In contrast, CB1R antagonists, selective CB2R agonists, and endocannabinoid metabolizing enzymes inhibitors alleviate DPN pain effectively with minimal side effects. This article provides a concise overview of the preclinical and clinical studies that have tested the therapeutic potential of targeting the endocannabinoid system to treat painful DPN.