The endocannabinoid system as a target for novel anxiolytic drugs

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:76

Article; Proceedings Paper

Patel, Sachin^1,2,3,4  Hill, Mathew N.^5,6,7,8  Cheer, Joseph F.^9,10  Wotjak, Carsten T.¹¹  Holmes, Andrew¹² 

[1] Vanderbilt Univ, Med Ctr, Dept Psychiat & Behav Sci, Nashville, TN USA

[2] Vanderbilt Univ, Vanderbilt Brain Inst, 221 Kirkland Hall, Nashville, TN 37235 USA

[3] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA

[4] Vanderbilt Univ, Med Ctr, Vanderbilt Kennedy Ctr Human Dev, Nashville, TN USA

[5] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada

[6] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada

[7] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB, Canada

[8] Univ Calgary, Dept Psychiat, Calgary, AB, Canada

[9] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA

[10] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA

[11] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, Munich, Germany

[12] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA

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

DOI  :  10.1016/j.neubiorev.2016.12.033

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Ltd.

【 授权许可】

Free