Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice

The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ9-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice. Abcb1a/b (−/−), Abcg2 (−/−) and wild-type (WT) mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (−/−) and Abcg2 (−/−) mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (−/−) mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis

Assessing the performance of domestic heating controls in a whole house test facility

The energy consumed by domestic space heating systems represents a considerable share of the energy consumed in the UK. At the same time up to a quarter of English homes have inadequate controls on the central heating systems. Current modelling tools, and results from the limited field trials that have been carried out, are problematic due to the influence of the behaviour of occupants and variability of weather conditions. The Salford Energy House is a full-sized end terrace house built within a climate controlled laboratory. This allows a house of typical construction to be extensively analysed while completely disconnected from the unpredictability of weather conditions and human behaviour. This paper presents a series of tests carried out in the Salford Energy House into the effectiveness of installing room thermostats and thermostatic radiator valves. Savings of 40% in terms of energy consumption, cost and CO2 were achieved. The results should be regarded with caution in terms of their extent and application to real homes, but represent a significant contribution to the gap in current knowledge due to the ability to isolate the performance of homes from uncooperative variables, and a potential base for the development of more effective modelling tools