Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid-modulating enzyme fatty acid amide hydrolase.

OBJECTIVES: The study aimed to identify nutmeg compounds that indirectly interact with the endocannabinoid system through inhibition of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes. METHODS: Thirteen compounds were screened for FAAH and MAGL inhibition. Compounds demonstrating significant FAAH inhibition were evaluated to determine the halfmaximal inhibitory concentration (IC50 ). The most potent compound was investigated in the elevated plus maze (EPM) rodent anxiety model. KEY FINDINGS: Three compounds, licarin A (9), 5'-methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 µm ± 2.02, 4.57 µm ± 0.66 and 38.29 µm ± 6.18, respectively. None of the purified compounds showed significant MAGL inhibition. Because of its relative high potency and selectivity, compound 8 was further evaluated in the EPM animal model of anxiety. The compound showed significant increase in number of open arm entries (P < 0.05) when administered at 120 mg/kg dose. No effect was observed on the locomotor activity. CONCLUSIONS: Results collected introduce active nutmeg compounds as potential leads for further development. Of the three compounds, 8 possesses highest potency and FAAH selectivity as well as anxiolytic activity. Furthermore, in vivo testing in appropriate behavioural animal paradigms is warranted.

Problem signs in law school: Fostering attorney well-being early in professional training.

Attorneys suffer from high rates of stress, alcoholism, and mental health problems that are costly for the legal system and impair their abilities to serve their clients. There is some indication that these problems begin in law school. The present study assessed a cohort of law students at an American law school for their reported levels of stress, depression, anxiety, substance use, and overall adjustment/coping. Findings indicate that law students suffer from high levels of stress, anxiety, depression, and alcohol use, and that these problem behaviors fluctuate throughout the course of law school. We discuss the implications for law student/lawyer well-being and legal education.

How people evaluate others with social anxiety disorder: A comparison to depression and general mental illness stigma.

Despite the availability of effective interventions, most individuals with social anxiety disorder do not seek treatment. Given their fear of negative evaluation, socially anxious individuals might be especially susceptible to stigma concerns, a recognized barrier for mental health treatment. However, very little is known about the stigma specific to social anxiety disorder. In a design similar to Feldman and Crandall (2007), university undergraduate students read vignettes about target individuals with a generic mental illness label, major depressive disorder, and social anxiety disorder. Subjects rated each of 3 people in the vignettes on social distance and 17 dimensions including dangerousness, heritability and prevalence of the disorder, and gender ratio. Results indicated that being male and not having experience with mental health treatment was associated with somewhat greater preferred social distance. Multiple regression analyses revealed that being embarrassed by the disorder and dangerousness predicted social distance across all 3 vignettes. The vignette for social anxiety disorder had the most complex model and included work impairment, more common among women, and more avoidable. These results have implications for understanding the specific aspects of the stigma associated with social anxiety disorder. Public service messages to reduce stigma should focus on more accurate information about dangerousness and mental illness, given this is an established aspect of mental illness stigma. More nuanced messages about social anxiety might be best incorporated into the treatment referral process and as part of treatment.