Discovery of Selective Cannabinoid CB2 Receptor Agonists by High-Throughput Screening.

The endocannabinoid system (ECS) plays a diverse role in human physiology ranging from the regulation of mood and appetite to immune modulation and the response to pain. Drug development that targets the cannabinoid receptors (CB1 and CB2) has been explored; however, success in the clinic has been limited by the psychoactive side effects associated with modulation of the neuronally expressed CB1 that are enriched in the CNS. CB2, however, are expressed in peripheral tissues, primarily in immune cells, and thus development of CB2-selective drugs holds the potential to modulate pain among other indications without eliciting anxiety and other undesirable side effects associated with CB1 activation. As part of a collaborative effort among industry and academic laboratories, we performed a high-throughput screen designed to discover selective agonists or positive allosteric modulators (PAMs) of CB2. Although no CB2 PAMs were identified, 167 CB2 agonists were discovered here, and further characterization of four select compounds revealed two with high selectivity for CB2 versus CB1. These results broaden drug discovery efforts aimed at the ECS and may lead to the development of novel therapies for immune modulation and pain management with improved side effect profiles.

Enhancing the mental health promotion component of a health and personal development programme in Irish schools.

This study set out to examine the impact of a health and personal development programme (the Social, Personal and Health Education Programme) which had been 'enhanced' by the addition of a mental health promotion component. Students aged 12-16 years attending 17 secondary schools were randomly allocated as clusters to participate in either the standard programme (SP) or the enhanced programme (EP). Both programmes were delivered over an eight-month period. Questionnaires assessing help-seeking, emotional and behavioural difficulties and students' views of school social environment were completed by students in both groups at pre-intervention, post-intervention and at six-month follow-up. One thousand and seventy-two students participated. Analyses were carried out on the 782 students (72.9%) for whom data were available at all three time points. Both groups showed improvement over time in terms of emotional and behavioural difficulties, with male students identified as 'at risk' in the EP showing significantly greater improvements than males 'at risk' in the SP. Although there were few differences in outcomes between the groups, males identified as 'at risk' appeared to benefit selectively from the EP.