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Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors.

ABSTRACT: Recent studies have demonstrated anxiolytic potential of pharmacological endocannabinoid (eCB) augmentation approaches in a variety of preclinical models. Pharmacological inhibition of endocannabinoid-degrading enzymes, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), elicit promising anxiolytic effects in rodent models with limited adverse behavioral effects, however, the efficacy of dual FAAH/MAGL inhibition has not been investigated. In the present study, we compared the effects of FAAH (PF-3845), MAGL (JZL184) and dual FAAH/MAGL (JZL195) inhibitors on (1) anxiety-like behaviors under non-stressed and stressed conditions, (2) locomotor activity and body temperature, (3) lipid levels in the brain and (4) cognitive functions. Behavioral analysis showed that PF-3845 or JZL184, but not JZL195, was able to prevent restraint stress-induced anxiety in the light-dark box assay when administered before stress exposure. Moreover, JZL195 treatment was not able to reverse foot shock-induced anxiety-like behavior in the elevated zero maze or light-dark box. JZL195, but not PF-3845 or JZL184, decreased body temperature and increased anxiety-like behavior in the open-field test. Overall, JZL195 did not show anxiolytic efficacy and the effects of JZL184 were more robust than that of PF-3845 in the models examined. These results showed that increasing either endogenous AEA or 2-AG separately produces anti-anxiety effects under stressful conditions but the same effects are not obtained from simultaneously increasing both AEA and 2-AG.

SUBMITTER: Bedse G

PROVIDER: S-EPMC5917016 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors.

Bedse Gaurav G Bluett Rebecca J RJ Patrick Toni A TA Romness Nicole K NK Gaulden Andrew D AD Kingsley Philip J PJ Plath Niels N Marnett Lawrence J LJ Patel Sachin S

Translational psychiatry 20180426 1

Recent studies have demonstrated anxiolytic potential of pharmacological endocannabinoid (eCB) augmentation approaches in a variety of preclinical models. Pharmacological inhibition of endocannabinoid-degrading enzymes, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), elicit promising anxiolytic effects in rodent models with limited adverse behavioral effects, however, the efficacy of dual FAAH/MAGL inhibition has not been investigated. In the present study, we compa ...[more]

PMID: 29695817

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Project description:ImportanceChildren with strabismus have poorer functional vision and decreased quality of life than those without strabismus.ObjectiveTo evaluate the association between strabismus and mental illness among children.Design, setting, and participantsThis cross-sectional study analyzed claims data from the OptumLabs Data Warehouse, a longitudinal deidentified commercial insurance claims database, from 12 005 189 patients enrolled in the health plan between January 1, 2007, and December 31, 2017. Eligibility criteria included age younger than 19 years at the time of strabismus diagnosis, enrollment in the health plan between 2007 and 2018, and having at least 1 strabismus claim based on International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes. Controls were children in the same database with no eye disease codes other than refractive error reported. Demographic characteristics and mental illness claims were compared. Statistical analysis was conducted from December 1, 2018, to July 31, 2021.Main outcomes and measuresPresence of mental illness claims.ResultsAmong the 12 005 189 patients (6 095 523 boys [50.8%]; mean [SD] age, 8.0 [5.9] years) in the study, adjusted odds ratios for the association of mental illnesses with strabismus were 2.01 (95% CI, 1.99-2.04) for anxiety disorder, 1.83 (95% CI, 1.76-1.90) for schizophrenia, 1.64 (95% CI, 1.59-1.70) for bipolar disorder, 1.61 (95% CI, 1.59-1.63) for depressive disorder, and 0.99 (95% CI, 0.97-1.02) for substance use disorder. There was a moderate association between each strabismus type (esotropia, exotropia, and hypertropia) and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder; odds ratios ranged from 1.23 (95% CI, 1.17-1.29) for the association between esotropia and bipolar disorder to 2.70 (95% CI, 2.66-2.74) for the association between exotropia and anxiety disorder.Conclusions and relevanceThis cross-sectional study suggests that there was a moderate association between strabismus and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder but not substance use disorder. Recognizing that these associations exist should encourage mental illness screening and treatment for patients with strabismus.

Dataset Information

Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors.

Publications

Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors.

Similar Datasets

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