Modulation of CB1 cannabinoid receptor alters the electrophysiological properties of cerebellar Purkinje cells in harmaline-induced essential tremor.

Essential tremor (ET) is one of the most common motor disorders with debilitating effects on the affected individuals. The endocannabinoid system is widely involved in cerebellar signaling. Therefore, modulation of cannabinoid-1 receptors (CB1Rs) has emerged as a novel target for motor disorders.

Exploring the relationships between psychological variables and loot box engagement, part 2: exploratory analyses of complex relationships.

In a pre-registered survey linked to this paper (Exploring the relationships between psychological variables and loot box engagement, part 1: pre-registered hypotheses), we confirmed bivariate associations between engagement with loot boxes (purchasable randomized rewards in video games) and measures of problem gambling, problem video gaming, impulsivity, gambling cognitions, experiences of game-related 'flow', psychological distress and reduced wellbeing. However, these variables have complex relationships, so to gain further insights, we analysed the dataset (1495 gamers who purchase loot boxes and 1223 purchasers of non-randomized content) in a series of Bayesian mixed-effects multiple regressions with a zero-inflation component. The results challenge some well-established results in the literature, including associations between loot box engagement and problematic gambling measures, instead suggesting that this relationship might be underpinned by shared variance with problem video gaming and gambling-related cognitions.

Exploring the relationships between psychological variables and loot box engagement, part 1: pre-registered hypotheses.

Loot boxes are purchasable randomized rewards in video games that share structural and psychological similarities with gambling. Systematic review evidence has established reproducible associations between loot box purchasing and both problem gambling and problem video gaming, perhaps driven by a range of overlapping psychological processes (e.g.

Cannabinoid treatments in epilepsy and seizure disorders.

Cannabis has been used to treat convulsions and other disorders since ancient times. In the last few decades, preclinical animal studies and clinical investigations have established the role of cannabidiol (CBD) in treating epilepsy and seizures and support potential therapeutic benefits for cannabinoids in other neurological and psychiatric disorders. Here, we comprehensively review the role of cannabinoids in epilepsy.

The DNA damage response in advanced ovarian cancer: functional analysis combined with machine learning identifies signatures that correlate with chemotherapy sensitivity and patient outcome.

Background: Ovarian cancers are hallmarked by chromosomal instability. New therapies deliver improved patient outcomes in relevant phenotypes, however therapy resistance and poor long-term survival signal requirements for better patient preselection. An impaired DNA damage response (DDR) is a major chemosensitivity determinant.

Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsies, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G-protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored.

"I can't skip it": does free report improve accuracy in false memories?

Strategic monitoring of recognition memory by children and adults was examined using a semantic DRM procedure. Children (7- and 10-year-olds) and adults (overall  = 393) studied lists of semantically related words either incidentally or intentionally and were tested with old items, new items and critical lures to judge as old or new. Participants either made a decision about every item they saw (forced report), or they had the opportunity to withhold answers they were uncertain about (free report).

A Fiber Alginate Co-culture Platform for the Differentiation of mESC and Modeling of the Neural Tube.

Alginate hydrogels are a commonly used substrate for 3D cell culture. These naturally derived biomaterials are highly tunable, biocompatible, and can be designed to mimic the elastic modulus of the adult brain at 1% w/v solution. Recent studies show that the molecular weight of the alginate can affect cell viability and differentiation.

Anticonvulsive Properties of Cannabidiol in a Model of Generalized Seizure Are Transient Receptor Potential Vanilloid 1 Dependent.

Highly purified cannabidiol (CBD) (approved as Epidiolex in the United States) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut or Dravet syndrome in four randomized controlled trials. CBD possesses affinity for many target classes with functional effects relevant to the pathophysiology of many disease types, including epilepsy. Although the mechanism of action of CBD underlying the reduction of seizures in humans is unknown, transient receptor potential vanilloid 1 (TRPV1) represents a plausible target because (1) CBD activates and then desensitizes TRPV1, (2) TRPV1 is overexpressed in models of temporal lobe epilepsy and patients with epilepsy, (3) and TRPV1 modulates neuronal excitability.

Cannabidiol improves survival and behavioural co-morbidities of Dravet syndrome in mice.

Background And Purpose: Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and co-morbidities such as anxiety, depression, autism, motor dysfunction and memory deficits. Cannabidiol is an approved anticonvulsive drug in the United States and Europe for seizures associated with Dravet syndrome in patients 2 years of age and older. We investigated its potential to prevent premature mortality and improve associated co-morbidities.

The proposed mechanisms of action of CBD in epilepsy.

Highly purified cannabidiol (CBD) (approved as Epidiolex in the United States and as EPIDYOLEX from the EU agency) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut or Dravet syndrome in four randomized controlled trials. While the mechanism of action of CBD underlying the reduction of seizures in humans is unknown, CBD possesses affinity for multiple targets, across a range of target classes, resulting in functional modulation of neuronal excitability, relevant to the pathophysiology of many disease types, including epilepsy. Here we present the pharmacological data supporting the role of three such targets, namely Transient receptor potential vanilloid-1 (TRPV1), the orphan G protein-coupled receptor-55 (GPR55) and the equilibrative nucleoside transporter 1 (ENT-1).

Anabolic androgenic steroid abuse in the United Kingdom: An update.

Anabolic androgenic steroids (AASs) are prescribed for medical conditions related to low testosterone. Abuse of AASs has surged as they become recognised as potent image enhancement drugs. The primary goal of most abusers is to obtain a more attractive outward appearance.

Diving and mental health: the potential benefits and risks from a survey of recreational scuba divers.

Introduction: Scuba diving is physically and cognitively demanding. Medical guidance regarding physical and mental health (MH) issues and related prescribed medication is often based on limited evidence. There is a paucity of data concerning diving with MH issues.

The best treatment option(s) for adult and elderly patients with chronic primary musculoskeletal pain: a protocol for a systematic review and network meta-analysis.

Background: Chronic primary musculoskeletal pain (CPMP) is one subcategory of the new classification of chronic primary pain for the upcoming ICD-11, defined as chronic pain in the muscles, bones, joints, or tendons that persists or recurs for more than 3 months and is associated with significant emotional distress or functional disability. An array of pharmacological, psychological, physical, complementary, and rehabilitative interventions is available for CPMP, for which previous research has demonstrated varying effect sizes with regard to effectiveness in pain reduction and other main outcomes. This highlights the need for the synthesis of all available evidence.

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.

Background And Purpose: Epidiolex™, a form of highly purified cannabidiol (CBD) derived from Cannabis plants, has demonstrated seizure control activity in patients with Dravet syndrome, without a fully elucidated mechanism of action. We have employed an unbiased approach to investigate this mechanism at a cellular level.

Experimental Approach: We use a tractable biomedical model organism, Dictyostelium, to identify a protein controlling the effect of CBD and characterize this mechanism.

Refractory depression - cost-effectiveness of radically open dialectical behaviour therapy: findings of economic evaluation of RefraMED trial.

Background: Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.AimsTo estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627).

Refractory depression - mechanisms and efficacy of radically open dialectical behaviour therapy (RefraMED): findings of a randomised trial on benefits and harms.

Background: Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.

Aims: To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).

The Cannabinoid-Like Compound, VSN16R, Acts on Large Conductance, Ca-Activated K Channels to Modulate Hippocampal CA1 Pyramidal Neuron Firing.

Large conductance, Ca-activated K (BK) channels are widely expressed in the central nervous system, where they regulate action potential duration, firing frequency and consequential neurotransmitter release. Moreover, drug action on, mutations to, or changes in expression levels of BK can modulate neuronal hyperexcitability. Amongst other potential mechanisms of action, cannabinoid compounds have recently been reported to activate BK channels.

Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol.

Background: Muscle wasting, anorexia, and metabolic dysregulation are common side-effects of cytotoxic chemotherapy, having a dose-limiting effect on treatment efficacy, and compromising quality of life and mortality. Extracts of Cannabis sativa, and analogues of the major phytocannabinoid Δ9-tetrahydrocannabinol, have been used to ameliorate chemotherapy-induced appetite loss and nausea for decades. However, psychoactive side-effects limit their clinical utility, and they have little efficacy against weight loss.

Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene. CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation.

Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models.

Objective: Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus-spontaneous recurrent seizures (RISE-SRS) model of temporal lobe epilepsy (TLE).

Validation of the person-centred coordinated care experience questionnaire (P3CEQ).

Background: Measuring patient experiences of healthcare is increasingly emphasized as a mechanism to measure, benchmark and drive quality improvement, clinical effectiveness and patient safety at both national and local NHS level. Person-centred coordinated care (P3C) is the conjunction of two constructs; person-centred care and care coordination. It is a complex intervention requiring support for changes to organizational structure and the behaviour of professionals and patients.

Functional imagery training versus motivational interviewing for weight loss: a randomised controlled trial of brief individual interventions for overweight and obesity.

Objective: Functional Imagery Training (FIT) is a new brief motivational intervention based on the Elaborated Intrusion theory of desire. FIT trains the habitual use of personalised, affective, goal-directed mental imagery to plan behaviours, anticipate obstacles, and mentally try out solutions from previous successes. It is delivered in the client-centred style of Motivational Interviewing (MI).

Intention insertion: Activating an action's perceptual consequences is sufficient to induce non-willed motor behavior.

It feels intuitive that our actions are intentional, but there is considerable debate about whether (and how) humans control their motor behavior. Recent ideomotor theories of action argue that action intentions are fundamentally perceptual, that actions are not only controlled by anticipating-imagining-their intended perceptual consequences, but are also initiated when this action effect activation is strong. Here, the authors report a study (plus a replication) that provides direct evidence for this proposal, showing that even nonintended actions are executed when their effects are activated strongly enough.