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The endocannabinoid system in the amygdala and modulation of fear.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric condition characterized by lifelong complex cognitive, emotional and behavioral phenotype. Although many individuals that experience trauma are able to gradually diminish their emotional responding to trauma-related stimuli over time, known as extinction learning, individuals suffering from PTSD are impaired in this capacity. An inability to decline this initially normal and adaptive fear response, can be confronted with exposure-based therapies, often in combination with pharmacological treatments. Due to the complexity of PTSD, currently available pharmacotherapeutics are inadequate in treating the deficient extinction observed in many PTSD patients. To develop novel therapeutics, researchers have exploited the conserved nature of fear and stress-associated behavioral responses and neurocircuits across species in an attempt to translate knowledge gained from preclinical studies into the clinic. There is growing evidence on the endocannabinoid modulation of fear and stress due to their 'on demand' synthesis and degradation. Involvement of the endocannabinoids in fear extinction makes the endocannabinoid system very attractive for finding effective therapeutics for trauma and stress related disorders. In this review, a brief introduction on neuroanatomy and circuitry of fear extinction will be provided as a model to study PTSD. Then, the endocannabinoid system will be discussed as an important component of extinction modulation. In this regard, anandamide degrading enzyme, fatty acid amide hydrolase (FAAH) will be exemplified as a target identified and validated strongly from preclinical to clinical translational studies of enhancing extinction.

SUBMITTER: Gunduz-Cinar O

PROVIDER: S-EPMC7511205 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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The endocannabinoid system in the amygdala and modulation of fear.

Gunduz-Cinar Ozge O

Progress in neuro-psychopharmacology & biological psychiatry 20200923

Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric condition characterized by lifelong complex cognitive, emotional and behavioral phenotype. Although many individuals that experience trauma are able to gradually diminish their emotional responding to trauma-related stimuli over time, known as extinction learning, individuals suffering from PTSD are impaired in this capacity. An inability to decline this initially normal and adaptive fear response, can be confronted ...[more]

PMID: 32976951

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Project description:Currently, the involvement of the endocannabinoid system in cancer development and possible options for a cancer-regressive effect of cannabinoids are controversially discussed. In recent decades, a number of preclinical studies have shown that cannabinoids have an anticarcinogenic potential. Therefore, especially against the background of several legal simplifications with regard to the clinical application of cannabinoid-based drugs, an extended basic knowledge about the complex network of the individual components of the endocannabinoid system is required. The canonical endocannabinoid system consists of the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol as well as the Gi/o protein-coupled transmembrane cannabinoid receptors CB1 and CB2. As a result of extensive studies on the broader effect of these factors, other fatty acid derivatives, transmembrane and intracellular receptors, enzymes and lipid transporters have been identified that contribute to the effect of endocannabinoids when defined in the broad sense as "extended endocannabinoid system." Among these additional components, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid-binding protein family, additional cannabinoid-activated G protein-coupled receptors such as GPR55, members of the transient receptor family, and peroxisome proliferator-activated receptors were identified as targets for possible strategies to combat cancer progression. Other endocannabinoid-related fatty acids such as 2-arachidonoyl glyceryl ether, O-arachidonoylethanolamine, N-arachidonoyldopamine and oleic acid amide showed an effect via cannabinoid receptors, while other compounds such as endocannabinoid-like substances exert a permissive action on endocannabinoid effects and act via alternative intracellular target structures. This review gives an overview of the modulation of the extended endocannabinoid system using the example of anticancer cannabinoid effects, which have been described in detail in preclinical studies.

Dataset Information

The endocannabinoid system in the amygdala and modulation of fear.

Publications

The endocannabinoid system in the amygdala and modulation of fear.

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