A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro

Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta(9)-tetrahydrocannabinol (Delta(9)-THC), and even Delta(9)-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta(9)-THC (1microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta(9)-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1microM); interestingly, the potentiation by Delta(9)-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta(9)-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1(-/-)) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1(-/-) cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta(9)-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta(9)-THC (due to attenuation of some of the central Delta(9)-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content

Potential of Brassic rapa, Cannabis sativa, Helianthus annuus and Zea mays for phytoextraction of heavy metals from calcareous dredged sediment derived soils

Remediation of soil pollution is one of the many current environmental challenges. Anthropogenic activity has resulted in the contamination of extended areas of land, the remediation of which is both invasive and expensive by conventional means. Phytoextraction of heavy metals from contaminated soils has the prospect of being a more economic in situ alternative. In addition, phytoextraction targets ecotoxicologically the most relevant soil fraction of these metals, i.e. the bioavailable fraction. Greenhouse experiments were carried out to evaluate the potential of four high biomass crop species in their potential for phytoextraction of heavy metals, with or without with the use of soil amendments (EDTA or EDDS). A calcareous dredged sediment derived surface soil, with high organic matter and clay content and moderate levels of heavy metal pollution, was used in the experiments. No growth depression was observed in EDTA or EDDS treated pots in comparison to untreated controls. Metal accumulation was considered to be low for phytoextraction purposes, despite the use of chelating agents. The low observed shoot concentrations of heavy metals were attributed to the low phytoavailability of heavy metals in this particular soil substrate. The mobilising effects induced by EDTA in the soil were found to be too long-lived for application as a soil amendment in phytoextraction. Although EDDS was found to be more biodegradable, higher effect half lives were observed than reported in literature or observed in previous experiments. These findings caution against the use of any amendment, biodegradable or otherwise, without proper investigation of its effects and the longevity thereof. (C) 2005 Elsevier Ltd. All rights reserved.

Official warnings on thromboembolism risk with oral contraceptives fail to inform users adequately

Following the 1995 “pill scare” relating to the risk of venous thrombosis from taking second- or third-generation oral contraceptives, the Committee on Safety of Medicines (CSM) withdrew their earlier recommended restrictions on the use of third-generation pills and published recommended wording to be used in patient information leaflets. However, the effectiveness of this wording has not been tested. An empirical study (with 186 pill users, past users, and non-users) was conducted to assess understanding, based on this wording, of the absolute and relative risk of thrombosis in pill users and in pregnancy. The results showed that less than 12% of women in the (higher education) group fully understood the absolute levels of risk from taking the pill and from being pregnant. Relative risk was also poorly understood, with less than 40% of participants showing full understanding, and 20% showing no understanding. We recommend that the CSM revisit the wording currently provided to millions of women in the UK.

Involving users in expert system development

The ultimate criterion of success for interactive expert systems is that they will be used, and used to effect, by individuals other than the system developers. A key ingredient of success in most systems is involving users in the specification and development of systems as they are being built. However, until recently, system designers have paid little attention to ascertaining user needs and to developing systems with corresponding functionality and appropriate interfaces to match those requirements. Although the situation is beginning to change, many developers do not know how to go about involving users, or else tackle the problem in an inadequate way. This paper discusses the need for user involvement and considers why many developers are still not involving users in an optimal way. It looks at the different ways in which users can be involved in the development process and describes how to select appropriate techniques and methods for studying users. Finally, it discusses some of the problems inherent in involving users in expert system development, and recommends an approach which incorporates both ethnographic analysis and formal user testing.

Cannabis constituents modulate ∆9-tetrahydrocannabinol-induced hyperphagia in rats

Rationale The hyperphagic effect of ∆9-tetrahydrocannabinol (∆9THC) in humans and rodents is well known. However, no studies have investigated the importance of ∆9THC composition and any influence other non-∆9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified ∆9THC, synthetic ∆9THC (dronabinol), and ∆9THC botanical drug substance (∆9THC-BDS), a ∆9THC-rich standardized extract comparable in composition to recreationally used cannabis. Methods Adult male rats were orally dosed with purified ∆9THC, synthetic ∆9THC, or ∆9THC-BDS, matched for ∆9THC content (0.34–2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following ∆9THC administration. Data were then analyzed in terms of hourly intake and meal patterns. Results All three ∆9THC substances tested induced significant hyperphagic effects at doses ≥0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified ∆9THC and ∆9THC-BDS. Conclusion All ∆9THC compounds displayed classical ∆9THC effects on feeding, significantly increasing short-term intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified ∆9THC and ∆9THC-BDS are due to non-∆9THC cannabinoids present in ∆9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate ∆9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.

Quantitative comparison between the use of 3D vs 2D visualization tools to present building design proposals to non-spatial skilled end users

Information technology in construction (ITC) has been gaining wide acceptance and is being implemented in the construction research domains as a tool to assist decision makers. Most of the research into visualization technologies (VT) has been on the wide range of 3D and simulation applications suitable for construction processes. Despite its development with interoperability and standardization of products, VT usage has remained very low when it comes to communicating and addressing the needs of building end-users (BEU). This paper argues that building end users are a source of experience and expertise that can be brought into the briefing stage for the evaluation of design proposals. It also suggests that the end user is a source of new ideas promoting innovation. In this research a positivistic methodology that includes the comparison of 3D models and the traditional 2D methods is proposed. It will help to identify "how much", if anything, a non-spatial specialist can gain in terms Of "understanding" of a particular design proposal presented, using both methods.

Learning to talk to users in participatory design situations

In participatory design situations the competence of the facilitator will influence the opportunities for a user group to become engaged in the process of design. Based on the observation of the conversations from a series of design workshops, the performance of design facilitation expertise by an expert architect is compared with a less experienced architectural graduate. The skills that are the focus of this research are the conversational competences deployed by architects to engage users in the design of an architectural project. The difference between the conversational behaviour of a project architect and a less experienced graduate was observed to illustrate with examples the effect the performance of facilitation had on the opportunity for user engagement in design, and of learning the skill of facilitation that occurred in these situations.