Cannabinoids and Anxiety

Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 2)

Abstract

The term cannabinoids encompasses compounds produced by the plant Cannabis sativa, such as Δ 9-tetrahydrocannabinol, and synthetic counterparts. Their actions occur mainly through activation of cannabinoid type 1 (CB1) receptors. Arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG) serve as major endogenous ligands (endocannabinoids) of CB1 receptors. Hence, the cannabinoid receptors, the endocannabinoids, and their metabolizing enzymes comprise the endocannabinoid system. Cannabinoids induce diverse responses on anxiety- and fear-related behaviors. Generally, low doses tend to induce anxiolytic-like effects, whereas high doses often cause the opposite. Inhibition of endocannabinoid degradation seems to circumvent these biphasic effects by enhancing CB1 receptor signaling in a temporarily and spatially restricted manner, thus reducing anxiety-like behaviors. Pharmacological blockade or genetic deletion of CB1 receptors, in turn, primarily exerts anxiogenic-like effects and impairments in extinction of aversive memories. Interestingly, pharmacological blockade of Transient Receptor Potential Vanilloid Type-1 (TRPV1) channel, which can be activated by anandamide as well, has diametrically opposite consequences. This book chapter summarizes and conceptualizes our current knowledge about the role of (endo)cannabinoids in fear and anxiety and outlines implications for an exploitation of the endocannabinoid system as a target for new anxiolytic drugs.

Keywords

Cannabinoids Endocannabinoids Fear Anxiety Stress 

Abbreviations

2-AG

2-Arachidonoyl glycerol (endocannabinoid; i.e., activates CB1 receptors)

AA-5HT

Arachidonoyl serotonin (synthetic inhibitor of FAAH-mediated endocannabinoid degradation and TRPV1 antagonist)

AEA

Anandamide or arachidonoyl ethanolamide (endocannabinoid and endovanilloid; i.e., activates CB1 receptors and TRPV1)

AM251

(Synthetic CB1 receptor antagonist)

AM404

(Synthetic inhibitor of endocannabinoid uptake and FAAH-mediated degradation)

CB1

Cannabinoid type 1 receptor

CB2

Cannabinoid type 2 receptor

CBD

Cannabidiol (phytocannabinoid)

CP-55940

(Synthetic CB1 receptor agonist)

Cre/loxP

(Recombinatory system used in conditional mouse mutagenesis)

FAAH

Fatty acid amide hydrolase (major degrading enzyme of AEA)

GABA

Gama-aminobutyric acid (major inhibitory transmitter of the brain)

GPR55

(G-protein-coupled cannabinoid receptor)

HU210

(Synthetic CB1 receptor agonist)

JZL184

(Synthetic inhibitor of MGL-mediated endocannabinoid degradation)

MGL

Monoacylglycerol lipase (major degrading enzyme of AEA)

PAG

Periaqueductal grey (matter brain structure orchestrating fear responses)

PPARα

(cannabinoid receptor)

SB366971

(Synthetic TRPV1 antagonist)

SR141716A

Rimonabant/acompliaTM (synthetic CB1 receptor antagonist)

SR144528

(Synthetic CB2 receptor antagonist)

Δ9-THC

Δ 9-Tetrahydrocannabinol (phytocannabinoid; major psychoactive ingredient of Cannabis sativa)

TRPV1

Transient receptor potential vanilloid type-1 channel

UCM707

(Synthetic inhibitor of endocannabinoid uptake)

URB597

(Synthetic inhibitor of FAAH-mediated endocannabinoid degradation)

VDM11

(Synthetic inhibitor of endocannabinoid uptake)

WIN-55212-2

(Synthetic CB1 receptor agonist)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of PharmacologyFederal University of Minas GeraisBelo HorizonteBrazil
  2. 2.Max Planck Institute of PsychiatryNeural Plasticity/Mouse Behaviour GroupMunichGermany

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