A Tale of Two Towns: A Comparative Study Exploring the Possibilities and Pitfalls of Social Capital among People Seeking Recovery from Substance Misuse.

BACKGROUND: Social capital has become an influential concept in debating and understanding the modern world. Within the drug and alcohol sector, the concept of 'recovery capital' has gained traction with researchers suggesting that people who have access to such capital are better placed to overcome their substance use-related problems than those who do not (Cloud and Granfield, 2008), leading to requests for interventions that focus on building social capital networks (Neale & Stevenson, 2015). While accepting that the concept of social capital has enormous potential for addressing the problems associated with drug use, this paper also considers its 'dark side'. METHODS: Data were drawn from semi-structured interviews with 180 participants including 135 people who use drugs and 45 people who formerly used drugs. RESULTS: High levels of trust, acquired through the establishment of dense social networks, are required to initiate recovery. However, these 'strong bonds' may also lead to the emergence of what is perceived by others as an exclusive social network that limits membership to those who qualify and abide by the 'rules' of the recovery community, particularly around continuous abstinence. CONCLUSIONS: Depending on the nature of the networks and the types of links participants have into them being socially connected can both inhibit and encourage recovery. Therefore, the successful application of social capital within the drugs and alcohol field requires a consideration of not only the presence or absence of social connections but their nature, the value they produce, and the social contexts within which they are developed.

Post-COVID-19 syndrome risk factors and further use of health services in East England.

Post-COVID syndrome, defined as symptoms persisting for more than twelve weeks after the diagnosis of COVID-19, has been recognised as a new clinical entity in the context of SARS-CoV-2 infection. This study was conducted to characterise the burden and predictors for post-COVID-19 syndrome in the local population. It was a community-based web-survey study conducted in Norfolk, East England, UK. We sent the survey to patients with confirmed COVID-19 infection by real-time polymerase chain reaction by December 6th, 2020. Questions related to the pre-COVID and post-COVID level of symptoms and further healthcare use. Baseline characteristics were collected from the primary care records. Logistic regression analysis was conducted to establish predictors for post-COVID-19 syndrome and further healthcare utilisation. Of 6,318 patients, survey responses were obtained from 1,487 participants (23.5%). Post-COVID-19 syndrome symptoms were experienced by 774 (52.1%) respondents. Male sex compared to female sex was a factor protective of post-COVID symptoms; relative risk (RR) 0.748, 95% confidence interval (CI), 0.605-0.924. Body mass index was associated with a greater risk of developing post-COVID-19 symptoms (RR 1.031, 95% CI, 1.016-1.047, for 1 kg/m2). A total of 378 (25.4%) people used further health services after their index COVID-19 infection, of whom 277 (73.2%) had post-COVID symptoms. Male sex was negatively associated with the use of further health services (RR 0.618, 95% CI, 0.464-0.818) whereas BMI was positively associated (RR 1.027, 95% CI, 1.009-1.046). Overall, post-COVID-19 symptoms increased the probability of using health services with RR 3.280, 95% CI, 2.540-4.262. This survey of a large number of people previously diagnosed with COVID-19 across East England shows a high prevalence of self-reported post-COVID-19 syndrome. Female sex and BMI were associated with an increased risk of post-COVID-19 syndrome and further utilisation of healthcare.

Δ9-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats.

PURPOSE: We assessed the anticonvulsant potential of the phytocannabinoid Δ9-tetrahydrocannabivarin (Δ9-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats. METHODS: Δ9-THCV was applied before (10 µm Δ9-THCV) or during (10-50 µm Δ9-THCV) epileptiform activity induced by Mg²(+) -free extracellular media in adult rat PC slices and measured using multielectrode array (MEA) extracellular electrophysiologic techniques. The actions of Δ9-THCV on CB1 receptors were examined using [³H]SR141716A competition binding and [³5S]GTPγS assays in rat cortical membranes. Effects of Δ9-HCV (0.025-2.5 mg/kg) on pentylenetetrazole (PTZ)-induced seizures in adult rats were also assessed. RESULTS: After induction of stable spontaneous epileptiform activity, acute Δ9 -THCV application (≥ 20 µm) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 µm Δ9-THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, Δ9-THCV acted as a CB1 receptor ligand, displacing 0.5 nm [³H]SR141716A with a Ki∼290 nm, but exerted no agonist stimulation of [³5S]GTPγS binding. In PTZ-induced seizures in vivo, 0.25 mg/kg Δ9-THCV significantly reduced seizure incidence. DISCUSSION: These data demonstrate that Δ9-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.

Protocol for a randomized controlled trial of the Breaking Free Online Health and Justice program for substance misuse in prison settings.

BACKGROUND: Substance misuse, including problematic drug and alcohol use, are significant issues in society that can have multiple detrimental effects. Many people access support for their substance misuse during prison sentences, due to the associations between substance misuse and offending, and the high proportion of the prison population who have drug and alcohol issues. Breaking Free Online Health and Justice is a computer-assisted therapy program that has been developed to support substance-involved offenders to address their substance misuse and associated offending within prison settings. METHODS: This will be a parallel-group randomized controlled trial of 4-week Breaking Free Online Health and Justice program as an adjunct to standard treatment for substance misuse, in comparison to standard treatment only, in a male Category D open prison. Interventional and control groups will be compared in terms of the changes in their scores on multiple measures from baseline to post-treatment assessment at 4-weeks, and then 3- and 6-months follow-up. Participants will be adult male offenders serving sentences in prison in England who have demonstrable difficulties with drugs and/or alcohol for at least the past 12-months. The primary outcome measure will be self-reported substance misuse, with secondary outcomes being standardized psychometric assessments of substance dependence, mental health, biopsychosocial functioning, quality of life and post-release offending. Other secondary measures will include frequency of completion of specific intervention strategies in the program. DISCUSSION: This study will examine whether Breaking Free Online Health and Justice as an adjunct to standard substance misuse interventions in prisons, improves outcomes for substance-involved offenders receiving interventions in custodial settings. Findings from the study will be used to inform further developments of the program and potential improvements to custodial treatment. TRIALS REGISTRATION: ISRCTN09846981 .

Cholinergic modulation of intrinsic fibre-evoked excitatory transmission contains a nicotinic component in immature but not adult rat piriform cortex, in vitro.

The piriform cortex (PC) is highly prone to epileptogenesis, particularly in immature animals, where decreased muscarinic modulation of PC intrinsic fibre excitatory neurotransmission is implicated as a likely cause. However, whether higher levels of acetylcholine (ACh) release occur in immature vs. adult PC remains unclear. We investigated this using in vitro extracellular electrophysiological recording techniques. Intrinsic fibre-evoked extracellular field potentials (EFPs) were recorded from layers II to III in PC brain slices prepared from immature (P14-18) and adult (P>40) rats. Adult and immature PC EFPs were suppressed by eserine (1 microM) or neostigmine (1 microM) application, with a greater suppression in immature (approximately 40%) than adult (approximately 30%) slices. Subsequent application of atropine (1 microM) reversed EFP suppression, producing supranormal (approximately 12%) recovery in adult slices, suggesting that suppression was solely muscarinic ACh receptor-mediated and that some 'basal' cholinergic 'tone' was present. Conversely, atropine only partially reversed anticholinesterase effects in immature slices, suggesting the presence of additional non-muscarinic modulation. Accordingly, nicotine (50 microM) caused immature field suppression (approximately 30%) that was further enhanced by neostigmine, whereas it had no effect on adult EFPs. Unlike atropine, nicotinic antagonists, mecamylamine and methyllycaconitine, induced immature supranormal field recovery (approximately 20%) following anticholinesterase-induced suppression (with no effect on adult slices), confirming that basal cholinergic 'tone' was also present. We suggest that nicotinic inhibitory cholinergic modulation occurs in the immature rat PC intrinsic excitatory fibre system, possibly to complement the existing, weak muscarinic modulation, and could be another important developmentally regulated system governing immature PC susceptibility towards epileptogenesis.

A psychometric typology of U.K. domestic violence offenders.

A number of studies have described subtypes of domestically violent men, and the heterogeneity of domestically violent men is well established. The aim of the current study was to investigate the distribution of subtypes using psychometric measures in convicted domestically violent offenders in England. Four subtypes of offenders were identified: low pathology, borderline, narcissistic, and antisocial. These subtypes were broadly comparable with the family-only, dysphoric/borderline, and generally violent/antisocial types proposed by Holtzworth-Munroe and Stuart. The majority of the sample (60%) best fit the generally violent/antisocial profile. However, the reliance on psychometric measurement and lack of corroborative evidence from partners means that further research is necessary to test these findings.

Drug spend and acquisitive offending by substance misusers.

AIM: The need to generate income to fund drug misuse is assumed to be a driver of involvement in acquisitive crime. We examined the influence of drug misuse expenditure, and other factors, on acquisitive offending. METHODS: Clients (N=1380) seeking drug treatment within 94 of 149 Drug Action Teams (DATs) across England completed a comprehensive survey, incorporating validated scales and self-report measures, such as levels of drug and alcohol use and offending. RESULTS: Forty per cent (N=554) had committed acquisitive crime in the previous month. Regression analysis showed that acquisitive offending was associated with the presence of problematic use of crack cocaine, poly-drug use, sharing injecting equipment, unsafe sex, overdose risk, higher drug spend, unemployment, reduced mental wellbeing, and younger age. CONCLUSIONS: Rates of acquisitive crime among drug users are high. Drug using offenders can be distinguished from drug using non-offenders by problematic crack cocaine use, younger age, income-related factors, and indicators of a chaotic life style and complex needs. Behavioural and demographic factors were associated more strongly with acquisitive crime than drug use expenditure, suggesting that the need to finance drug use is not necessarily the main factor driving acquisitive offending by drug users.

Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥ 10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic-clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.

WITHDRAWN: Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

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Anticholinesterase-induced epileptiform activity in immature rat piriform cortex slices, in vitro.

PURPOSE: Acute in vitro brain slice models are commonly used to study epileptiform seizure generation and to test anti-epileptic drug action. Seizure-like activity can be readily induced by manipulating external ionic concentrations or by adding convulsant agents to the bathing medium. We previously showed that epileptiform bursting was induced in slices of immature (P14-28) rat piriform cortex (PC) by applying oxotremorine-M, a potent muscarinic receptor agonist. Here, we examined whether raising levels of endogenous acetylcholine (ACh) by exposure to anticholinesterases, could also induce epileptiform events in immature (P12-14) or early postnatal (P7-9) rat PC brain slices. METHODS: The effects of anticholinesterases were investigated in rat PC neurons using both extracellular MEA (P7-9 slices) and intracellular (P12-14 slices) recording methods. RESULTS: In P7-9 slices, eserine (20 microM) or neostigmine (20 microM) induced low amplitude, low frequency bursting activity in all three PC cell layers (I-III), particularly layer III, where neuronal muscarinic responsiveness is known to predominate. In P12-14 neurons, neostigmine produced a slow depolarization together with an increase in input resistance and evoked cell firing. Depolarizing postsynaptic potentials evoked by intrinsic fibre stimulation were selectively depressed although spontaneous bursting was not observed. Neostigmine effects were blocked by atropine (1 microM), confirming their muscarinic nature. We conclude that elevation of endogenous ACh by anticholinesterases can induce bursting in early postnatal PC brain slices, further highlighting the epileptogenic capacity of this brain region. However, this tendency declines with further development, possibly as local inhibitory circuit mechanisms become more dominant.