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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

Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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Toxins 2019, 11(5), 275; https://doi.org/10.3390/toxins11050275
Received: 24 April 2019 / Revised: 10 May 2019 / Accepted: 12 May 2019 / Published: 15 May 2019
(This article belongs to the Special Issue From Toxins to Drugs)
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 activity in the central nervous system, which in turn regulates food intake and underlies the development of metabolic syndrome. Indeed, these findings led to the clinical testing of globally acting CB1R blockers for obesity and various metabolic complications. However, their therapeutic potential was halted due to centrally mediated adverse effects. Recent observations that highlighted the key role of the peripheral eCB system in metabolic regulation led to the preclinical development of various novel compounds that block CB1R only in peripheral organs with very limited brain penetration and without causing behavioral side effects. These unique molecules, which effectively ameliorate obesity, type II diabetes, fatty liver, insulin resistance, and chronic kidney disease in several animal models, are likely to be further developed in the clinic and may revive the therapeutic potential of blocking CB1R once again. View Full-Text
Keywords: Cannabis; marijuana; CB1 receptor; central CB1 receptor blockade; peripheral CB1 receptor blockade Cannabis; marijuana; CB1 receptor; central CB1 receptor blockade; peripheral CB1 receptor blockade
MDPI and ACS Style

Hirsch, S.; Tam, J. 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. Toxins 2019, 11, 275.

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