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Cannabinoids and the Brain$
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Linda A. Parker

Print publication date: 2017

Print ISBN-13: 9780262035798

Published to MIT Press Scholarship Online: September 2017

DOI: 10.7551/mitpress/9780262035798.001.0001

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PRINTED FROM MIT PRESS SCHOLARSHIP ONLINE (www.mitpress.universitypressscholarship.com). (c) Copyright The MIT Press, 2021. All Rights Reserved. An individual user may print out a PDF of a single chapter of a monograph in MITSO for personal use.date: 23 September 2021

The Endocannabinoid System

The Endocannabinoid System

(p.19) 2 The Endocannabinoid System
Cannabinoids and the Brain

Linda A. Parker

The MIT Press

The endocannabinoid system was only discovered about 25 years ago, but it is now known to be a major modulator of synaptic activity throughout the brain. CB1 receptors are located on presynaptic terminals of neurons that release other neurotransmitters and the action of agonists of these receptors is to turn-off neurotransmitter release. These receptors are ubiquitously located, indeed they are the most widely distributed receptor system in the brain. Administration of THC by use of marijuana activates all CB1 receptors, producing global activation. On the other hand, endocannabinoids (anandamide and 2-AG) are produced where and when they are needed from depolarized post-synaptic neurons, serving as retrograde messengers to act on nearby presynaptic neurons. The fine-tuned regulation of synaptic activity is the primary function of this neuromodulatory system that plays a major role in protection of neurons. The duration of action of these “on demand” endocannabinoids is brief because they are hydrolysed enzymatically by Fatty Acid Amide Hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Newly developed FAAH and MAGL inhibitors provide a therapeutic opportunity to boost the action of AEA and 2-AG respectively for up to 24 hr, where and when they are produced naturally. Preclinical evidence indicates that FAAH and MAGL inhibitors have therapeutic potential in relief of pain, anxiety, depression and nausea, in the absence of psychoactive side effects of global activation of CB1 receptors produced by marijuana.

Keywords:   Anandamide, 2-arachidonyl glycerol (2-AG), CB1 receptor, CB2 receptor, Monoacylglycerol lipase (MAGL), Fatty acid amide hydrolase (FAAH), Endocannabinoid, TRPV1, GPR55

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