Cannabinoids and Anxiety

  • Fabrício A. Moreira
  • Carsten T. WotjakEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 2)


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.


Cannabinoids Endocannabinoids Fear Anxiety Stress 



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


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


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


(Synthetic CB1 receptor antagonist)


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


Cannabinoid type 1 receptor


Cannabinoid type 2 receptor


Cannabidiol (phytocannabinoid)


(Synthetic CB1 receptor agonist)


(Recombinatory system used in conditional mouse mutagenesis)


Fatty acid amide hydrolase (major degrading enzyme of AEA)


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


(G-protein-coupled cannabinoid receptor)


(Synthetic CB1 receptor agonist)


(Synthetic inhibitor of MGL-mediated endocannabinoid degradation)


Monoacylglycerol lipase (major degrading enzyme of AEA)


Periaqueductal grey (matter brain structure orchestrating fear responses)


(cannabinoid receptor)


(Synthetic TRPV1 antagonist)


Rimonabant/acompliaTM (synthetic CB1 receptor antagonist)


(Synthetic CB2 receptor antagonist)


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


Transient receptor potential vanilloid type-1 channel


(Synthetic inhibitor of endocannabinoid uptake)


(Synthetic inhibitor of FAAH-mediated endocannabinoid degradation)


(Synthetic inhibitor of endocannabinoid uptake)


(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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