Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation

The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non‐tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa‐induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra‐, inter‐ and extra‐cellular mechanisms of action, we demonstrate that non‐Δ9tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.

An analysis of verbal responses to music in a group of adult non-specialists

In a workshop setting, two pieces of recorded music were presented to a group of adult non-specialists; a key feature was to set up structured discussion within which the respondents considered each piece of music as a whole and not in its constituent parts. There were two areas of interest, namely to explore whether the respondents were likely to identify the musical features or to make extra-musical associations and, to establish the extent to which there would be commonality and difference in their approach to formulating the verbal responses. An inductive approach was used in the analysis of data to reveal some of the working theories underpinning the intuitive musicianship of the adult non-specialist listener. Findings have shown that, when unprompted by forced choice responses, the listeners generated responses that could be said to be information-poor in terms of musical features but rich in terms of the level of personal investment they made in formulating their responses. This is evidenced in a number of connections they made between the discursive and the non-discursive, including those which are relational and mediated by their experiences. Implications for music education are considered.

Phytocannabinoids as novel therapeutic agents in CNS disorders

The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB1 receptors by the major pCB, Δ9-tetrahydrocannabinol (Δ9-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ9-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ9tetrahydrocannabivarin (Δ9-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ9-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ9-THC pCB-based medicines.

Therapeutic and cytotoxic effects of the novel antipsoriasis codrug, naproxyl-dithranol, on HaCaT cells

A novel topical codrug, naproxyl–dithranol (Nap-DTH), in which dithranol and naproxen are linked via an ester in a 1:1 ratio to form a single chemical entity, was synthesized. The antiproliferative, anti-inflammatory and toxic effects of Nap-DTH were assessed, at the cellular level, using various in vitro methods. Cultured HaCaT keratinocytes were treated with Nap-DTH, and the cellular effects were compared with those of the parent compounds, individually and as a 1:1 mixture of naproxen:dithranol to mimic 1:1 in situ liberation from Nap-DTH. The results demonstrate that Nap-DTH did not modify proliferation and only exhibited slight toxic effects after 24 h at concentrations >21 μM. At a lower concentration (3.4 μM), Nap-DTH did not alter cell proliferation or inflammation, which suggests that the codrug is therapeutically inert. Relating to this, the 1:1 mixture of naproxen:dithranol exhibited the lowest toxic effect and the highest antiproliferative effect on HaCaT keratinocytes compared to dithranol at the same concentration. Moreover, the 1:1 mixture exhibited a reduced inflammatory effect compared to dithranol alone, as reflected by the upregulation of cyclooxygenase-2 by 45% and 136%, respectively. In spite of the 1:1 mixture showing a greater downregulation of Ki-67 and a 2-fold reduction of proliferating cell nuclear antigen (both cellular markers of proliferation) than dithranol, dithranol showed a much greater induction of cleaved caspase-3 protein expression (upregulated by 287%, compared to 85% for the 1:1 mixture). This suggests that when dithranol was administered with naproxen, inhibition of cell growth plays a more important role in the antiproliferation effects than the induction of apoptotic cell death. These results confirm that the codrug would lead to a better therapeutic profile and fewer adverse effects compared to its parent compounds.

Meteorological phenomena in Western classical orchestral music

Depictions of the weather are common throughout the arts. Unlike in the visual arts, however, there has been little study of meteorological inspiration in music. This article catalogues and analyzes the frequencies with which weather is depicted in a sample of classical orchestral music. The depictions vary from explicit mimicry using traditional and specialized orchestral instruments, through to subtle suggestions. It is found that composers are generally influenced by their own environment in the type of weather they choose to represent. As befits the national stereotype, British composers seem disproportionately keen to depict the UK's variable weather patterns and stormy coastline

'John James' and 'The White Stones' p. 71: Music, rhyme, and home

An essay relating 'The Dragon House' by John James to 'Thoughts on the Esterhazy Court Uniform' by J. H. Prynne