Possible actions of cannabidiol in obsessive-compulsive disorder by targeting the WNT/β-catenin pathway

The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future. Copyright © 2012 Elsevier Inc. All rights reserved.

Despite significant advances in the study of obsessive-compulsive disorder (OCD), important questions remain about the disorder's public health significance, appropriate diagnostic classification, and clinical heterogeneity. These issues were explored using data from the National Comorbidity Survey Replication, a nationally representative survey of US adults. A subsample of 2073 respondents was assessed for lifetime Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) OCD. More than one quarter of respondents reported experiencing obsessions or compulsions at some time in their lives. While conditional probability of OCD was strongly associated with the number of obsessions and compulsions reported, only small proportions of respondents met full DSM-IV criteria for lifetime (2.3%) or 12-month (1.2%) OCD. OCD is associated with substantial comorbidity, not only with anxiety and mood disorders but also with impulse-control and substance use disorders. Severity of OCD, assessed by an adapted version of the Yale-Brown Obsessive Compulsive Scale, is associated with poor insight, high comorbidity, high role impairment, and high probability of seeking treatment. The high prevalence of subthreshold OCD symptoms may help explain past inconsistencies in prevalence estimates across surveys and suggests that the public health burden of OCD may be greater than its low prevalence implies. Evidence of a preponderance of early onset cases in men, high comorbidity with a wide range of disorders, and reliable associations between disorder severity and key outcomes may have implications for how OCD is classified in DSM-V.

Circadian rhythms are approximately 24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional-translational autoregulatory loop generates molecular oscillations of 'clock genes' at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.