The "Entourage Effect": Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders.

Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, 'cannabis' is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the "entourage effect" is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

Mentalizing Self and Other and Affect Regulation Patterns in Anorexia and Depression.

The study aimed to examine two constructs: general mentalizing processes and the specific component of affective mentalizing regarding self and others alongside the construct of affect regulation patterns in female adolescent and young adult inpatients with anorexia nervosa (AN; n = 41), depression (n = 20) and controls (n = 53). We further examined the predictive ability of affect regulation to eating-disorder (ED) symptoms beyond that of the mentalizing variables, and their potential role in mediating between mentalizing, depression and ED symptoms. We used tools assessing reflective functioning (RF), complex emotion recognition and theory of mind (ToM), alexithymia, affect regulation, depression, and ED symptoms. The AN and depression groups exhibited lower general mentalizing and higher alexithymia, emotional reactivity, and emotional cutoff patterns than controls, but showed no greater disturbance in ToM. The two clinical groups did not differ on any of these variables. Elevated mentalizing and adequate affect regulation patterns separately predicted lower severity of ED symptoms. Nonetheless, affect regulation did not add to the predictive value of mentalizing variables. Specifically, elevated alexithymia, and depressive symptomatology, but not RF, predicted greater ED symptomatology. Moreover, alexithymia directly accounted for elevated ED symptoms and also indirectly connected with ED symptoms via emotional hyperactivation and elevated depressive symptoms. These findings suggest that deficiencies in mentalization and affect regulation are not unique to AN, but may rather associated with psychopathology in general. Nonetheless, alexithymia and depression may increase ED-related symptomatology. Affect regulation deficiencies are mainly related with depressive symptoms and emotional hyperactivation is indirectly related with AN via the depressive symptoms.

Adherence to antidepressant medications is associated with reduced premature mortality in patients with cancer: A nationwide cohort study.

BACKGROUND: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all-cause mortality in a population-based cohort of patients with cancer. MATERIALS AND METHODS: We conducted a 4-year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (<20%), poor (20-50%), moderate (50-80%), and good (>80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality. RESULTS: During 1,051,489 person-years at risk follow-up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83-0.95), 0.77 (95% CI: 0.66-0.72), and 0.80 (95% CI: 0.76-0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42-1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04-1.15]; P < .0001), low socioeconomic status (HR 1.1, [95% CI: 1.03-1.17]; P < .0001) and more physical comorbidities. CONCLUSIONS: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all-cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients.

Exploring Particular Facets of Cognitive Emotion Regulation and Their Relationships With Nonsuicidal Self-Injury Among Adolescents.

Background: Nonsuicidal self-injury (NSSI) has been found to be associated with poor emotion regulation. Aims: The goal of this study was to examine the association of multidimensional cognitive emotion regulation strategies with NSSI among adolescents and compare the different patterns of NSSI. Method: A sample of 594 high-school students (54.4% boys; mean age = 14.96 years), from five regional schools across Israel, were assessed for five facets of cognitive emotion regulation strategies (acceptance, refocus on planning, positive refocusing, putting into perspective, and positive reappraisal) and NSSI behaviors using validated scales. Participants were allocated into three groups: repetitive NSSI (more than six occasions of NSSI; 7.1%), occasional NSSI (at least one incident but less than six; 8.3%), and no NSSI (84.6%). Results: Analysis of covariance, controlling for gender and depression symptoms, revealed that students with NSSI reported higher levels of acceptance, but lower levels of refocus on planning and putting into perspective. Limitations: The study used a cross-sectional design, which was a limitation. Conclusion: These findings demonstrate that particular cognitive emotion regulation strategies differ substantially in their relationship with NSSI. Adolescents who focus on planning and putting stressful situations into perspective may have increased resilience, whereas adolescents who are accepting of negative events that have happened may be more prone to maladaptive coping behaviors.

Positive margin status in uterine cervix cone specimens is associated with persistent/recurrent high-grade dysplasia.

The frequency of positive cone margins and its significance in cervical intraepithelial neoplasia are under controversy. The purpose of the current study was to identify factors associated with positive cone margin status and to evaluate its clinical significance in high-grade cervical intraepithelial neoplasia. Medical records of women who underwent loop electrosurgical excision procedure at the Soroka Medical Center (January 2001-July 2011) were reviewed retrospectively. Patient age, extent of dysplasia, endocervical glands involvement, positive margin status, type of margin involved, degree of margin involvement, and postcone endocervical curettage results were evaluated as possible factors associated with persistent/recurrent disease. A total of 376 women were included in the study. Cone margin involvement was observed in 33% (endocervical-22%, ectocervical-8%, both margins-3%). Factors significantly associated with cone margin involvement were older age (older than 35 y), widespread dysplasia in the cone specimen (≥4 sections) (P<0.001 for each), and endocervical glands involvement (P=0.003). Fifty patients (13%) had persistent/recurrent disease. Involvement of the cone margins (focal: hazard ratio=17, P<0.001; extensive: hazard ratio=28, P<0.001) and older age (hazard ratio=1.18 for every 5 additional years, P=0.03) were associated with persistent/recurrent disease. We conclude that women older than 35 yr with widespread high-grade dysplasia in the cone specimen and involvement of endocervical glands are more likely to have positive cone margins. Positive cone margins, particularly when extensively involved, and increased patient age are associated with persistent/recurrent disease. These factors should be considered while planning for further management.

Post-conization endocervical curettage for estimating the risk of persistent or recurrent high-grade dysplasia.

OBJECTIVE: To evaluate the association between post-cone endocervical curettage (ECC) results, either alone or with cone margin status, and persistent/recurrent high-grade dysplasia after conization. METHODS: The medical records of 250 women who underwent a loop electrosurgical excision procedure with post-cone ECC at Soroka Medical Center, Be'er Sheva, Israel, between January 2001 and July 2011 were reviewed retrospectively. RESULTS: Thirty-one women (12.4%) had evidence of high-grade dysplasia in the ECC sample. Factors associated with positive ECC were being older than 35 years (P=0.004) and positive margin status (P=0.001). Twenty-nine patients (11.6%) had persistent/recurrent high-grade dysplasia. Both high-grade dysplasia in the ECC sample (hazard ratio, 2.31; P=0.032) and positive cone margins (hazard ratio, 23.4; P<0.001) were associated with persistent/recurrent disease. CONCLUSION: High-grade dysplasia in the ECC sample was associated with positive cone margin status. These 2 factors were both associated with persistent/recurrent disease. Among patients with positive cone margins, a combination of margin status and ECC was superior to margin status alone for estimating the probability of persistent/recurrent disease. For women with negative cone margins, ECC was less useful. Because ECC is valuable for assessing the risk of persistent/recurrent high-grade dysplasia in many cases, post-cone ECC should be performed routinely with conization.