Send to

Choose Destination
Neurosci Biobehav Rev. 2017 May;76(Pt A):56-66. doi: 10.1016/j.neubiorev.2016.12.033.

The endocannabinoid system as a target for novel anxiolytic drugs.

Author information

Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, USA; Vanderbilt Kennedy Center for Human Development, Vanderbilt University Medical Center, Nashville, USA.
Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada; Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Calgary, AB, Canada.
Department of Anatomy and Neurobiology and Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Max Planck Institute of Psychiatry, Department of Stress Neurobiology & Neurogenetics, Munich, Germany.
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Electronic address:


The endocannabinoid (eCB) system has attracted attention for its role in various behavioral and brain functions, and as a therapeutic target in neuropsychiatric disease states, including anxiety disorders and other conditions resulting from dysfunctional responses to stress. In this mini-review, we highlight components of the eCB system that offer potential 'druggable' targets for new anxiolytic medications, emphasizing some of the less well-discussed options. We discuss how selectively amplifying eCBs recruitment by interfering with eCB-degradation, via fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been linked to reductions in anxiety-like behaviors in rodents and variation in human anxiety symptoms. We also discuss a non-canonical route to regulate eCB degradation that involves interfering with cyclooxygenase-2 (COX-2). Next, we discuss approaches to targeting eCB receptor-signaling in ways that do not involve the cannabinoid receptor subtype 1 (CB1R); by targeting the CB2R subtype and the transient receptor potential vanilloid type 1 (TRPV1). Finally, we review evidence that cannabidiol (CBD), while representing a less specific pharmacological approach, may be another way to modulate eCBs and interacting neurotransmitter systems to alleviate anxiety. Taken together, these various approaches provide a range of plausible paths to developing novel compounds that could prove useful for treating trauma-related and anxiety disorders.


Amygdala; CB1 receptor; COX-2; Cannabis; Cortisol; Dopamine; Fear; Glucocorticoid; Hippocampus; PTSD; Prefrontal cortex; Stress

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center