Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo

Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the anti-epileptiform and anti-seizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01-100 muM) effects were assessed in vitro using the Mg(2+)-free and 4-aminopyridine (4-AP) models of status epilepticus-like epileptiform activity in hippocampal brain slices via multi-electrode array (MEA) recordings. In the Mg(2+)-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude (in CA1 and dentate gyrus (DG) regions) and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1, only at 100 muM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10 and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole (PTZ) model of generalised seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality in comparison to vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB(1) receptors and displayed no agonist activity in [(35)S]GTPgammaS assays in cortical membranes. These findings suggest that CBD acts to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel anti-epileptic drug (AED) in the unmet clinical need associated with generalised seizures.

A cost-effective high-throughput digital system for observation and acquisition of animal behavioral data

We have designed and implemented a low-cost digital system using closed-circuit television cameras coupled to a digital acquisition system for the recording of in vivo behavioral data in rodents and for allowing observation and recording of more than 10 animals simultaneously at a reduced cost, as compared with commercially available solutions. This system has been validated using two experimental rodent models: one involving chemically induced seizures and one assessing appetite and feeding. We present observational results showing comparable or improved levels of accuracy and observer consistency between this new system and traditional methods in these experimental models, discuss advantages of the presented system over conventional analog systems and commercially available digital systems, and propose possible extensions to the system and applications to nonrodent studies.

Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform bursting induced by 100M4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. It may also uncover additional modes of action that contribute to anti-epileptiform drug effects

Past, present and future precipitation in the Middle East: insights from models and observations

Anthropogenic changes in precipitation pose a serious threat to society—particularly in regions such as the Middle East that already face serious water shortages. However, climate model projections of regional precipitation remain highly uncertain. Moreover, standard resolution climate models have particular difficulty representing precipitation in the Middle East, which is modulated by complex topography, inland water bodies and proximity to the Mediterranean Sea. Here we compare precipitation changes over the twenty-first century against both millennial variability during the Holocene and interannual variability in the present day. In order to assess the climate model and to make consistent comparisons, this study uses new regional climate model simulations of the past, present and future in conjunction with proxy and historical observations. We show that the pattern of precipitation change within Europe and the Middle East projected by the end of the twenty-first century has some similarities to that which occurred during the Holocene. In both cases, a poleward shift of the North Atlantic storm track and a weakening of the Mediterranean storm track appear to cause decreased winter rainfall in southern Europe and the Middle East and increased rainfall further north. In contrast, on an interannual time scale, anomalously dry seasons in the Middle East are associated with a strengthening and focusing of the storm track in the north Mediterranean and hence wet conditions throughout southern Europe.

Auditory memory and the irrelevant sound effect: further evidence for changing state disruption

Four experiments investigate the hypothesis that irrelevant sound interferes with serial recall of auditory items in the same fashion as with visually presented items. In Experiment 1 an acoustically changing sequence of 30 irrelevant utterances was more disruptive than 30 repetitions of the same utterance (the changing-state effect; Jones, Madden, & Miles, 1992) whether the to-be-remembered items were visually or auditorily presented. Experiment 2 showed that two different utterances spoken once (a heterogeneous compound suffix; LeCompte & Watkins, 1995) produced less disruption to serial recall than 15 repetitions of the same sequence. Disruption thus depends on the number of sounds in the irrelevant sequence. In Experiments 3a and 3b the number of different sounds, the "token-set" size (Tremblay & Jones, 1998), in an irrelevant sequence also influenced the magnitude of disruption in both irrelevant sound and compound suffix conditions. The results support the view that the disruption of memory for auditory items, like memory for visually presented items, is dependent on the number of different irrelevant sounds presented and the size of the set from which these sounds are taken. Theoretical implications are discussed.

The influence of affective statements on performance on implicit and explicit memory tasks

Consumers are often exposed to brand names presented concurrently with information such as brand claims and warnings, prior to making product choices. As implicit memory has been implicated in the consumer choice process, two experiments were conducted to assess the influence of additional information, namely simple positive and negative statements, on implicit and explicit memory tasks. In Experiment 1, the mere presence of additional statements at study significantly reduced performance on a two-alternatives forced recognition task. However, the same manipulation had no effect on implicit preference judgement task performance. The valence of the accompanying information had no effect on either task. In Experiment 2, using modified implicit and explicit choice tasks, performance on the former was unaffected by statement valence, whereas the latter task was. Hence, positive priming was obtained for brand names previously shown with negative information. The results of the experiments are discussed in relation to both implicit memory and consumer choice.

Provision of information about drug side-effects to patients

To make informed decisions about taking medicinal drugs, people need accurate information about side-effects. A European Union guideline now recommends use of qualitative descriptions for five bands of risk, ranging from very rare (affecting < 0·01% of the population), to very common (>10%). We did four studies of more than 750 people, whom we asked to estimate the probability of having a side-effect on the basis of qualitative and quantitative descriptions. Our results showed that qualitative descriptions led to gross overestimation of risk. Until further work is done on how patients taking the drugs interpret these terms, the terms should not be used in drug information leaflets.

Communicating information about medication side effects: effects on satisfaction, perceived risk to health, and intention to comply

Previous research has shown that people's evaluations of explanations about medication and their intention to comply with the prescription are detrimentally affected by the inclusion of information about adverse side effects of the medication. The present study (Experiment 1) examined which particular aspects of information about side effects (their number, likelihood of occurrence, or severity) are likely to have the greatest effect on people's satisfaction, perception of risk, and intention to comply, as well as how the information about side effects interacts with information about the severity of the illness for which the medication was prescribed. Across all measures, it was found that manipulations of side effect severity had the greatest impact on people's judgements, followed by manipulations of side effect likelihood and then number. Experiments 2 and 3 examined how the severity of the diagnosed illness and information about negative side effects interact with two other factors suggested by Social Cognition models of health behaviour to affect people's intention to comply: namely, perceived benefit of taking the prescribed drug, and the perceived level of control over preventing or alleviating the side effects. It was found that providing people with a statement about the positive benefit of taking the medication had relatively little effect on judgements, whereas informing them about how to reduce the chances of experiencing the side effects had an overall beneficial effect on ratings.

Is 15 per cent very common? Informing people about the risks of medication side effects

Objectives - To assess the general public's interpretation of the verbal descriptors for side effect frequency recommended for use in medicine information leaflets by a European Union (EU) guideline, and to examine the extent to which differences in interpretation affect people's perception of risk and their judgments of intention to comply with the prescribed treatment. Method - Two studies used a controlled empirical methodology in which people were presented with a hypothetical, but realistic, scenario about visiting their general practitioner and being prescribed medication. They were given an explanation that focused on the side effects of the medicine, together with information about the probability of occurrence using either numerical percentages or the corresponding EU verbal descriptors. Interpretation of the descriptors was assessed. In study 2, participants were also required to make various judgments, including risk to health and intention to comply. Key findings - In both studies, use of the EU recommended descriptors led to significant overestimations of the likelihood of particular side effects occurring. Study 2 further showed that the "overestimation" resulted in significantly increased ratings of perceived severity of side effects and risk to health, as well as significantly reduced ratings of intention to comply, compared with those for people who received the probability information in numerical form. Conclusion - While it is recognised that the current findings require replication in a clinical setting, the European and national authorities should suspend the use of the EU recommended terms until further research is available to allow the use of an evidence-based approach.

Donald Broadbent : 12th annual Broadbent lecture

In the 12th annual Broadbent Lecture at the Annual Conference Dianne Berry outlined Broadbent’s explicit and implicit influences on psychological science and scientists.

Strengthening argumentation in medical explanations by text planning revision

Explanations are an important by-product of medical decisionsupport activities, as they have proved to favour compliance and correct treatment performance. To achieve this purpose, these texts should have a strong argumentation content and should adapt to emotional, as well as to rational attitudes of the Addressee. This paper describes how Rhetorical Sentence Planning can contribute to this aim: the rulebased plan discourse revision is introduced between Text Planning and Linguistic Realization, and exploits knowledge about the user personality and emotions and about the potential impact of domain items on user compliance and memory recall. The proposed approach originates from analytical and empirical evaluation studies of computer generated explanation texts in the domain of drug prescription. This work was partially supported by a British-Italian Collaboration in Research and Higher Education Project, which involved the Universities of Reading and of Bari, in 1996.

Evaluating explanations about drug prescriptions: effects of varying the nature of information about side effects and its relative position in explanations

This study evaluates computer-generated written explanations about drug prescriptions that are based on an analysis of both patient and doctor informational needs. Three experiments examine the effects of varying the type of information given about the possible side effects of the medication, and the order of information within the explanation. Experiment 1 investigated the effects of these two factors on people's ratings of how good they consider the explanations to be and of their perceived likelihood of taking the medication, as well as on their memory for the information in the explanation. Experiment 2 further examined the effects of varying information about side effects by separating out the contribution of number and severity of side effects. It was found that participants in this study did not “like” explanations that described severe side effects, and also judged that they would be less likely to take the medication if given such explanations. Experiment 3 therefore investigated whether information about severe side effects could be presented in such a way as to increase judgements of how good explanations are thought to be, as well as the perceived likelihood of adherence. The results showed some benefits of providing additional explanatory information.

Habituation and dishabituation to speech and office noise

The authors examined whether background noise can be habituated to in the laboratory by using memory for prose tasks in 3 experiments. Experiment 1 showed that background speech can be habituated to after 20 min exposure and that meaning and repetition had no effect on the degree of habituation seen. Experiment 2 showed that office noise without speech can also be habituated to. Finally, Experiment 3 showed that a 5-min period of quiet, but not a change in voice, was sufficient to partially restore the disruptive effects of the background noise previously habituated to. These results are interpreted in light of current theories regarding the effects of background noise and habituation; practical implications for office planning are discussed.

What do patients want to know about their medicines, and what do doctors want to tell them?: a comparative study

A two phase study is reported. In the first phase, we asked a number of doctors to rate a list of information categories (identified by Berry, Gillie and Banbury 1995) in terms of how important they felt it was for the items to be included in an explanation to a patient about a drug prescription. In the second phase, we presented a large sample of people with a scenario about visiting their doctor and being prescribed medication, together with an explanation about the prescription which was said to be provided by the doctor. Four different explanations were compared, which were either based on what people in our earlier study wanted to know about drug prescriptions or on what the doctors thought it was important lo tell them. We also manipulated whether or not the explanations conveyed negative information (e.g. about the possible side effects of the medication). The results showed that people 'preferred' the explanations based on what the participants in the earlier study wanted to know about their medicines, rather than those based on what the doctors thought they should be told. They also 'preferred' the explanations that did not convey negative information, rather than those that did convey some negative information. In addition, the inclusion of negative information affected ratings of likely compliance with the prescribed medication.