Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs.

Biomolecules
Thomas Murphy, Bernard Le Foll

Abstract

Obesity rates are increasing worldwide and there is a need for novel therapeutic treatment options. The endocannabinoid system has been linked to homeostatic processes, including metabolism, food intake, and the regulation of body weight. Rimonabant, an inverse agonist for the cannabinoid CB1 receptor, was effective at producing weight loss in obese subjects. However, due to adverse psychiatric side effects, rimonabant was removed from the market. More recently, we reported an inverse relationship between cannabis use and BMI, which has now been duplicated by several groups. As those results may appear contradictory, we review here preclinical and clinical studies that have studied the impact on body weight of various cannabinoid CB1 drugs. Notably, we will review the impact of CB1 inverse agonists, agonists, partial agonists, and neutral antagonists. Those findings clearly point out the cannabinoid CB1 as a potential effective target for the treatment of obesity. Recent preclinical studies suggest that ligands targeting the CB1 may retain the therapeutic potential of rimonabant without the negative side effect profile. Such approaches should be tested in clinical trials for validation.

References

Aug 26, 1976·Psychopharmacology·I GreenbergJ G Bernstein
Sep 1, 1986·Pharmacology, Biochemistry, and Behavior·R W FoltinM W Fischman
Jan 26, 1973·Science·D S Kreuz, J Axelrod
Dec 1, 1982·Cancer Treatment Reviews·L LembergerP Pence
Jan 1, 1997·Pharmacology & Therapeutics·R G Pertwee
Mar 24, 2000·European Journal of Pharmacology·D GiulianiF Ferrari
Apr 3, 2001·European Journal of Pharmacology·M D AcetoB B Martin
May 31, 2002·Pharmacological Reviews·A C HowlettR G Pertwee
Jul 5, 2002·Journal of Biochemistry·Takayuki Sugiura, Keizo Waku
Feb 20, 2003·European Journal of Pharmacology·Audrey L HildebrandtShawn C Black
Nov 5, 2003·Nature Reviews. Neuroscience·Daniele Piomelli
Mar 22, 2005·Psychopharmacology·Margaret HaneyRichard W Foltin
Sep 28, 2005·Journal of Addictive Diseases·Matthew WarrenMark Gold
Feb 14, 2006·Brain Research·Jian-Ping GongGeorge R Uhl
Feb 16, 2006·JAMA : the Journal of the American Medical Association·F Xavier Pi-SunyerUNKNOWN RIO-North America Study Group
Mar 17, 2006·Journal of Ethnopharmacology·Mohamed Ben Amar
Aug 9, 2006·The American Journal of Cardiology·Nicolas RodondiUNKNOWN Coronary Artery Risk Development in Young Adults (CARDIA) Study
Sep 14, 2006·Pharmacological Reviews·Pál PacherGeorge Kunos
Jan 17, 2007·International Journal of Obesity : Journal of the International Association for the Study of Obesity·M CôtéV Di Marzo
Jun 1, 2007·Journal of the International Association of Physicians in AIDS Care : JIAPAC·Edwin DejesusDaniel Pearce
Jun 22, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kelly S SinkJohn D Salamone
Jun 26, 2007·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Margaret HaneyRichard W Foltin
Oct 26, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Adam P ChambersKeith A Sharkey
Feb 7, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·I KunzW Schilling
Mar 14, 2008·European Journal of Pharmacology·Richard Z ChenTung M Fong
Jul 16, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A W HerlingW Kramer
Apr 16, 2009·American Journal of Physiology. Endocrinology and Metabolism·Joyce M RicheyRichard N Bergman

❮ Previous
Next ❯

Citations

Jan 7, 2021·Journal of Receptor and Signal Transduction Research·Fatma Nihan CankaraCaner Günaydın
Jan 28, 2021·International Journal of Molecular Sciences·Ana Lago-FernandezPaula Morales
Mar 27, 2021·Orphanet Journal of Rare Diseases·Edward H SchuchmanCalogera M Simonaro
Mar 31, 2021·Drug Discovery Today·Farah DeebaManju Sharma
May 1, 2021·International Journal of Molecular Sciences·Estefanía MorenoEnric I Canela
Jun 9, 2021·Molecular Brain·Hajar Miranzadeh MahabadiChangiz Taghibiglou

❮ Previous
Next ❯

Methods Mentioned

BETA
pharmacotherapy

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.