The endocannabinoid system as a target for novel anxiolytic drugs

Sachin Patel, Mathew N. Hill, Joseph F. Cheer, Carsten T. Wotjak, Andrew Holmes*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

124 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)56-66
Number of pages11
JournalNeuroscience and Biobehavioral Reviews
Volume76
DOIs
StatePublished - May 1 2017
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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