非表示:
キーワード:
ACID AMIDE HYDROLASE; POSTTRAUMATIC-STRESS-DISORDER; DORSOLATERAL
PERIAQUEDUCTAL GRAY; CANNABINOID CB1 RECEPTOR; MONOACYLGLYCEROL LIPASE
BLOCKADE; ELEVATED PLUS-MAZE; SUBSTRATE-SELECTIVE INHIBITION;
POSITRON-EMISSION-TOMOGRAPHY; VANILLOID TYPE-1 CHANNELS;
CENTRAL-NERVOUS-SYSTEMBehavioral Sciences; Neurosciences & Neurology; Stress; Fear; PTSD; COX-2; CB1 receptor; Cannabis; Dopamine;
Glucocorticoid; Cortisol; Amygdala; Hippocampus; Prefrontal cortex;
要旨:
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.
