Cannabis and cannabinoids as an alternative remedy in metabolic syndrome

Abstract

Metabolic syndrome (MetS), an epidemic defined as a group of interconnected physiological, biochemistry, clinical, and metabolic factors, directly increases the risk of cardiovascular disease, atherosclerosis, type 2 diabetes, and death. MetS therapy includes diet, physical exercise, and a poly-pharmacological intervention. Cannabis is mainly recognized for its recreational uses and has several medical applications for neurological diseases, due to its hypnotic, anxiolytic, antinociceptive, anti-inflammatory, and anticonvulsant activities. Although several clinical observations in Cannabis smokers suggest metabolic effects, its utility in metabolic disorders is unclear. This review aims to determine under what conditions Cannabis might be useful in the treatment of MetS. Cannabis contains 120 phytocannabinoids, of which Δ 9 -THC mediates its psychoactive effects. Cannabinoids exert biological effects through interactions with the endocannabinoid system, which modulates several physiologic and metabolic pathways through cannabinoid receptors (CB1/CB2). Signaling through both receptors inhibits neurotransmitter release. In general, endocannabinoid system stimulation in Cannabis smokers and Δ 9 -THC signaling through CB1 have been implicated in MetS development, obesity, and type 2 diabetes. In contrast, CB1 antagonists and non-psychotropic phytocannabinoids like cannabidiol reduce these effects through interactions with both cannabinoid and non-cannabinoid receptors. These pharmacological approaches represent a source of new therapeutic agents for MetS. However, more studies are necessary to support the therapeutic potential of Cannabis and cannabinoids in metabolic abnormalities.

Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity

“…CB1R activation contributes to systemic inflammation by increasing IL-6 and TNF-α expression. It leads to ROS formation as well as inflammation associated with diabetes, thus leading to the additional production of endocannabinoids, tissue injury, and well-known diabetic complications (e.g., neuropathy, cardiopathy, retinopathy, nephropathy) [ 154 ].…”

“…Thus, it was observed that by exposing isolated human as well as mouse islets to CB1R antagonists (AM251 and SR141716A (rimonabant)), an increase in β-cell proliferation was induced, which was also seen in mice injected with AM251, which presented larger islets. AM251 contributed to the better recovery of β-cells as well as to the mitosis of the remaining β-cells in mice treated with streptozotocin, a β-cell toxin [ 154 ].…”

“…This led to the attenuation of the mesolimbic dopamine system. At the peripheral level, rimonabant acts by decreasing the levels of circulating ghrelin, as well as gastrointestinal motility, thus reducing the absorption of nutrients [ 154 ].…”

“…Although promising at first, rimonabant was retracted from the pharmaceutical market because of the psychiatric disorders it caused, of which depression and an increase in suicidal thoughts are of most importance [ 154 ]. It is currently seen as a starting point for the development of other CB1R antagonists/inverse agonists that do not cross the blood–brain barrier and do not have its adverse profile.…”

“…Rimonabant is the first potent and selective CB1R antagonist/inverse agonist developed in 1994 [ 201 ], exhibiting both centrally and peripherally mediated metabolic effects [ 154 ]. Rimonabant was first approved as an anti-obesity medication in Europe in 2006, being indicated for obese and overweight patients with major metabolic comorbidities [ 202 ].…”