The potential of inhibitors of endocannabinoid metabolism as anxiolytic and antidepressive drugs--A practical view

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
Christopher J Fowler

Abstract

The endocannabinoid system, comprising cannabinoid CB1 and CB2 receptors, their endogenous ligands anandamide and 2-arachidonoylglyerol, and their synthetic and metabolic enzymes, are involved in many biological processes in the body, ranging from appetite to bone turnover. Compounds inhibiting the breakdown of anandamide and 2-arachidonoylglycerol increase brain levels of these lipids and thus modulate endocannabinoid signalling. In the present review, the preclinical evidence that these enzymes are good targets for development of novel therapies for anxiety and depression are discussed from a practical, rather than mechanistic, point of view. It is concluded that the preclinical data are promising, albeit tempered by problems of tolerance as well as effects upon learning and memory for irreversible monoacylglycerol lipase inhibitors, and limited by a focus upon male rodents alone. Clinical data so far has been restricted to safety studies with inhibitors of anandamide hydrolysis and a hitherto unpublished study on such a compound in elderly patients with major depressive disorders, but under the dose regimes used, they are well tolerated and show no signs of "cannabis-like" behaviours.

References

Aug 2, 1971·JAMA : the Journal of the American Medical Association·J A HalikasS B Guze
May 30, 2001·Neuroscience and Biobehavioral Reviews·P Palanza
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jack C SipeBenjamin F Cravatt
Jan 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lei WangGeorge Kunos
Jun 27, 2003·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Michelle ClunieRay Yip
Apr 14, 2004·The European Journal of Neuroscience·J HallerT F Freund
Aug 3, 2004·Nature Reviews. Drug Discovery·Ismail Kola, John Landis
Apr 6, 2005·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J C SipeE Beutler
Jun 21, 2005·Addictive Behaviors·Thomas F Denson, Mitchell Earleywine
Dec 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·G GobbiD Piomelli
Feb 2, 2006·Neuropharmacology·Balapal S BasavarajappaBasalingappa L Hungund
Feb 17, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Anita C HanssonMarkus Heilig
Oct 4, 2006·The Journal of Biological Chemistry·Binqing Q WeiBenjamin F Cravatt
Oct 19, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stephen A VarvelAron H Lichtman
Dec 14, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yuri A BlednovR Adron Harris
Feb 7, 2007·Psychopharmacology·Pattipati S NaiduAron H Lichtman
Dec 22, 2007·Pharmacology, Biochemistry, and Behavior·Nima NaderiFereshteh Motamedi
Apr 22, 2008·Addiction Biology·Fabrício A Moreira, Beat Lutz
Jun 27, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Vincenzo MicaleVincenzo Di Marzo
Sep 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Maxwell A RubyRonald M Krauss
Nov 26, 2008·Nature Chemical Biology·Jonathan Z LongBenjamin F Cravatt
Feb 3, 2009·The Journal of Pharmacology and Experimental Therapeutics·S J Enna, M Williams
Jul 8, 2009·Progress in Neuro-psychopharmacology & Biological Psychiatry·Sudhir N UmatheNishant S Jain
Sep 8, 2009·Trends in Pharmacological Sciences·Matthew N HillGabriella Gobbi
Oct 1, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Elizabeth J Rahn, Andrea G Hohmann
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jonathan Z LongBenjamin F Cravatt
Mar 30, 2010·Pharmacology, Biochemistry, and Behavior·F J Bermudez-SilvaF Rodriguez de Fonseca
Jun 24, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Francis Rodriguez BambicoGabriella Gobbi
Aug 24, 2010·Nature Neuroscience·Joel E SchlosburgBenjamin F Cravatt
Sep 23, 2010·Journal of Psychiatric Practice·Sheldon H Preskorn
Nov 30, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Felipe V GomesFrancisco S Guimarães
Dec 15, 2010·Pharmacology, Biochemistry, and Behavior·Steven G KinseyAron H Lichtman

❮ Previous
Next ❯

Citations

Dec 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Daisuke OgasawaraMario van der Stelt
Jun 25, 2015·Regulatory Toxicology and Pharmacology : RTP·David V GauvinTheodore J Baird
Sep 7, 2016·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Gabriela B L SpiacciLeonardo B Resstel
Jan 12, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Katherine M HolleranDanny G Winder
Jan 29, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessandro DeplanoValentina Onnis
Dec 22, 2020·Journal of Internal Medicine·C J Fowler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anxiety Disorders

Discover the latest research on anxiety disorders including agoraphobia, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder here.

Related Papers

Pharmacological Reviews
Jacqueline L Blankman, Benjamin F Cravatt
Current Opinion in Chemical Biology
Alessia LigrestiVincenzo Di Marzo
Annual Review of Pharmacology and Toxicology
Ken Mackie
Chemistry and Physics of Lipids
Sonya L PalmerA Makriyannis
© 2021 Meta ULC. All rights reserved