Changes in recreational drug use, reasons for those changes and their consequence during and after the COVID-19 pandemic in the UK.

Changes in drug use in the general population during the COVID-19 pandemic and their long-term consequences are not well understood. We employed natural language processing and machine learning to analyse a large dataset of self-reported rates of and reasons for drug use during the pandemic, along with their associations with anxiety, depression and substance use problems post-pandemic. Our findings revealed a transient decrease in drug use at the pandemic's peak, primarily attributed to reduced social opportunities.

Differences in fMRI-based connectivity during abstinence or interventions between heroin-dependent individuals and healthy controls.

The substantial personal, societal, and economic impacts of opioid addiction drive research investigating how opioid addiction affects the brain, and whether therapies attenuate addiction-related metrics of brain function. Evaluating the connectivity between brain regions is a useful approach to characterise the effects of opioid addiction on the brain. This work is a systematic narrative review of studies investigating the effect of abstinence or interventions on connectivity in people who are dependent on heroin (HD) and healthy controls (HC).

Exploratory study of associations between monetary reward anticipation brain responses and mu-opioid signalling in alcohol dependence, gambling disorder and healthy controls.

Alcohol dependence (AD) and gambling disorder (GD) are common addiction disorders with significant physical and mental health consequences. AD and GD are associated with dysregulated responses to reward which could be due to a common mechanism of dysregulated endogenous opioid signalling. We explored associations between reward anticipation responses, using the Monetary Incentive Delay (MID) functional magnetic resonance imaging (fMRI) task, and mu-opioid receptor (MOR) availability and endogenous opioid release capacity using [C]carfentanil positron emission tomography (PET), in 13 AD, 15 GD and 14 heathy control (HC) participants.

Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence.

Introduction: Negative affective states contribute to the chronic-relapsing nature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target.

A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial.

There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics.

Disturbances across whole brain networks during reward anticipation in an abstinent addiction population.

The prevalent spatial distribution of abnormalities reported in cognitive fMRI studies in addiction suggests there are extensive disruptions across whole brain networks. Studies using resting state have reported disruptions in network connectivity in addiction, but these studies have not revealed characteristics of network functioning during critical psychological processes that are disrupted in addiction populations. Analytic methods that can capture key features of whole brain networks during psychological processes may be more sensitive in revealing additional and widespread neural disturbances in addiction, that are the provisions for relapse risk, and targets for medication development.

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety.

Using Baclofen to Explore GABA-B Receptor Function in Alcohol Dependence: Insights From Pharmacokinetic and Pharmacodynamic Measures.

The role of GABA-B neurotransmission in addiction has recently received increased attention, with clinical trials indicating that baclofen, a GABA-B receptor agonist, may reduce alcohol consumption, craving and promote abstinence. However, the optimal dose to treat alcohol dependence is unclear with patients requesting and tolerating much higher doses of baclofen, compared with other clinical uses. We assessed the pharmacokinetics and pharmacodynamics (PK/PD) of baclofen to provide insight into GABA-B sensitivity in this patient group, relative to controls.

Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and polysubstance-dependent individuals.

Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance-dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened 'top-down' control over impulsive behaviour.

Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals.

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects.

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.

Objectives: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants.

Experimental Design: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity.

Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task.

There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards.

The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development.

5-HT radioligands for human brain imaging with PET and SPECT.

The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT(1A), 5-HT(1B), 5-HT(2A), and 5-HT(4) receptors, and for SERT.

Sleep and its disorders in translational medicine.

The study of sleep is a useful approach to studying the brain in psychiatric disorders and in investigating the effects of psychotropic drugs. Sleep physiology lends itself well to pharmacological and physiological manipulation, as it has the advantage of a functional output, the electroencephalograph, which is common to all mammals, and can be measured in freely moving (or naturally sleeping) animals under controlled laboratory conditions or in a naturalistic home environment. The complexity of sleep architecture varies between species but all share features which are comparable.

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls.

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system.

NAPSAQ-1: National Patient Sleep Assessment Questionnaire in depression.

Objectives. Sleep disturbance is a common feature of depression. Symptoms often persist after treatment of the depressive episode, representing a risk factor for relapse.

A translational, caffeine-induced model of onset insomnia in rats and healthy volunteers.

Rationale: Insomnia is a common and disabling complaint for which there is a need for improved treatments. Successful drug discovery relies on the use of appropriate animal models to assess likely outcome in the clinic.

Objectives: The purpose of this study was to develop a translational, caffeine-induced model of insomnia in rats and healthy volunteers.

In vitro and in vivo effect of BU99006 (5-isothiocyanato-2-benzofuranyl-2-imidazoline) on I2 binding in relation to MAO: evidence for two distinct I2 binding sites.

BU99006 is an irreversible I(2) ligand which selectively inactivates I(2) binding sites, making it an ideal tool with which to study I(2) site mechanism. We sought to determine the effects of BU99006 on I(2) binding in relation to monoamine oxidase (MAO), and the time course of these effects. In vitro, rat brain membranes that were pre-treated with 10 microM BU99006 showed no change in MAO activity, despite suffering a significant reduction in [(3)H]2BFI binding (52.

Antidepressants and REM sleep in Wistar-Kyoto and Sprague-Dawley rats.

Compared to other rat strains, the Wistar-Kyoto rats show increased amount of REM sleep, one of the characteristic sleep changes observed in depressed patients. The aims of this study were firstly to validate a simple sleep stage discriminator and then compare the effect of antidepressants on suppression of rapid eye movement (REM) sleep in Wistar-Kyoto rats and an outbred rat strain (Sprague-Dawley). Rats were implanted with telemetry transmitters with electroencephalogram/electromyogram electrodes.