Deconstructing delay discounting in human cocaine addiction using computational modelling and neuroimaging.

Background: A preference for sooner-smaller over later-larger rewards, known as delay discounting, is a candidate transdiagnostic marker of waiting impulsivity and a research domain criterion. While abnormal discounting rates have been associated with many psychiatric diagnoses and abnormal brain structure, the underlying neuropsychological processes remain largely unknown. Here, we deconstruct delay discounting into choice and rate processes by testing different computational models and investigate their associations with white matter tracts.

Atomoxetine Reduces Decisional Impulsivity in Human Cocaine Addiction.

Background: Impulsivity is a well-known determinant of maladaptive behavior in cocaine use disorder (CUD), but there are currently no effective strategies for managing excessive impulsivity. Growing evidence from preclinical and clinical studies suggests that atomoxetine, a selective noradrenaline reuptake inhibitor, is effective in improving impulse control in both healthy individuals and individuals with neuropsychiatric conditions.

Methods: We investigated the effects of atomoxetine on decisional impulsivity in patients with CUD.

Gut Hormones: Possible Mediators of Addictive Disorders?

Background: Alcohol and drug dependence are major health and economic burdens to society. One of the major challenges to reducing this burden will be to develop more effective and better tolerated medications that target alternative mechanisms in the brain. While the dopamine system has been well characterized for mediating the reward value of drugs, there is evidence that the endocrine system also conveys signals to the same neural systems using gut hormones.

Reduced brain connectivity underlying value-based choices and outcomes in stimulant use disorder.

Background: Patients with stimulant use disorder (SUD) show impairments when making value-based choices that are associated with disruptions in neural processing across brain networks. Making optimal choices requires learning from outcomes to update knowledge and further optimise ongoing behaviour. The optimal functioning of neural systems that underpin the ability to make favourable choices is an essential component for life functioning, and successful recovery in patients with SUD.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions.

[Stimulants : Current insights into the principles, diagnostics and treatment].

Background: Consumption of stimulant drugs, a heterogeneous group of addictive substances, has significantly increased in recent years with rising numbers of stimulant-associated intoxication and deaths.

Objective: To provide an overview of recent scientific evidence of the diagnosis and treatment of stimulant use disorders.

Material And Methods: A literature review of the neuropathology, clinical presentation, diagnostic criteria and evidence-based treatment for stimulant use disorders.

Evidence of Hypothalamic-Pituitary-Adrenal and -Gonadal Dysfunction in Cocaine-Addicted Men.

Introduction: Regular cocaine use has been associated with hormonal dysfunction including hypogonadism, which can lead to fatigue, reduced stamina, sexual dysfunction, and impaired quality of life. However, cocaine's endocrine effects are largely under-reported in the scientific addiction literature and, in many cases, are not addressed within treatment services. The low profile of these adverse effects might be attributable to a lack of awareness and linkage with cocaine use, such that they are recognized only when an acute/emergency problem arises.

Mismatch of Biological and Social Time in Cocaine-Addicted Men.

Introduction: Chronotype describes a person's preferential activity pattern during a 24-hour period, which may not be in line with their social lifestyle. A mismatch between biological and social time is known as "social jetlag," which has negative effects on wellbeing. Cocaine influences a person's activity levels, but very little is known about possible changes in chronotype of patients with cocaine use disorder (CUD).

The Modulatory Effects of Atomoxetine on Aberrant Connectivity During Attentional Processing in Cocaine Use Disorder.

Background: Cocaine use disorder is associated with cognitive deficits that reflect dysfunctional processing across neural systems. Because there are currently no approved medications, treatment centers provide behavioral interventions that have only short-term efficacy. This suggests that behavioral interventions are not sufficient by themselves to lead to the maintenance of abstinence in patients with cocaine use disorder.

Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio.

Genotype-by-diagnosis interaction influences self-control in human cocaine addiction.

Not everyone who uses drugs loses control over their intake, which is a hallmark of addiction. Although familial risk studies suggest significant addiction heritability, the genetic basis of vulnerability to drug addiction remains largely unknown. In the present study, we investigate the relationship between self-control, cocaine use, and the rs36024 single nucleotide polymorphism of the noradrenaline transporter gene (SLC6A2).

Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

Aims: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.

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.

Abnormal Brain Networks Related to Drug and Nondrug Reward Anticipation and Outcome Processing in Stimulant Use Disorder: A Functional Connectomics Approach.

Background: Drug addiction is associated with blunted neural responses to nondrug rewards, such as money, but heightened responses to drug cues that predict drug-reward outcomes. This dissociation underscores the role of incentive context in the attribution of motivational salience, which may reflect a narrowing toward drug-related goals. This hypothesis, however, has scarcely been investigated.

Morphometric similarity deviations in stimulant use disorder point towards abnormal brain ageing.

Chronic drug use negatively impacts ageing, resulting in diminished health and quality of life. However, little is known about biomarkers of abnormal ageing in stimulant drug users. Using morphometric similarity network mapping, a novel approach to structural connectomics, we first mapped cross-sectional morphometric similarity trajectories of ageing in the publicly available Rockland Sample (20-80 years of age,  = 665).

Detecting Small Vessel Pathology in Cocaine Use Disorder.

Background: Cocaine use is associated with an increased risk of cerebrovascular accidents. Small vessel pathology has been linked to the risk of stroke in cocaine users, but can be challenging to detect on conventional magnetic resonance (MR) scans. Fluid-attenuated inversion recovery (FLAIR) scans permit better resolution of small vessel lesions.

Drug Use in Night Owls May Increase the Risk for Mental Health Problems.

Drugs of abuse are widely known to worsen mental health problems, but this relationship may not be a simple causational one. Whether or not a person is susceptible to the negative effects of drugs of abuse may not only be determined by their addictive properties, but also the users' chronotype, which determines their daily activity patterns. The present study investigates the relationship between chronotype, drug use and mental health problems in a cross-sectional community sample.

Prefrontal Cortex Activation and Stopping Performance Underlie the Beneficial Effects of Atomoxetine on Response Inhibition in Healthy Volunteers and Those With Cocaine Use Disorder.

Background: Impaired response inhibition in individuals with cocaine use disorder (CUD) is hypothesized to depend on deficient noradrenergic signaling in corticostriatal networks. Remediation of noradrenergic neurotransmission with selective norepinephrine reuptake inhibitors such as atomoxetine may therefore have clinical utility to improve response inhibitory control in CUD.

Methods: We carried out a randomized, double-blind, placebo-controlled, crossover study with 26 participants with CUD and 28 control volunteers investigating the neural substrates of stop-signal inhibitory control.

Impaired Learning From Negative Feedback in Stimulant Use Disorder: Dopaminergic Modulation.

Background: Drug-induced alterations to the dopamine system in stimulant use disorder (SUD) are hypothesized to impair reinforcement learning (RL). Computational modeling enables the investigation of the latent processes of RL in SUD patients, which could elucidate the nature of their impairments.

Methods: We investigated RL in 44 SUD patients and 41 healthy control participants using a probabilistic RL task that assesses learning from reward and punishment separately.

Reduced Glutamate Turnover in the Putamen Is Linked With Automatic Habits in Human Cocaine Addiction.

Background: The balance between goal-directed behavior and habits has been hypothesized to be biased toward the latter in individuals with cocaine use disorder (CUD), suggesting possible neurochemical changes in the putamen, which may contribute to their compulsive behavior.

Methods: We assessed habitual behavior in 48 patients with CUD and 42 healthy control participants using a contingency degradation paradigm and the Creature of Habit Scale. In a subgroup of this sample (CUD: n = 21; control participants: n = 22), we also measured glutamate and glutamine concentrations in the left putamen using ultra-high-field (7T) magnetic resonance spectroscopy.

Feeding the addiction: Narrowing of goals to habits.

Whilst the initiation of cocaine use is typically goal-directed and motivated by the rewarding effects of the drug, drug-taking can become habitual over time, rendering the user less sensitive to cocaine's hedonic value. Experimental studies suggest that patients with cocaine use disorder (CUD) are particularly prone to develop habits, even in non-drug related contexts. CUD patients have previously been shown to consume higher levels of high-calorie foods and report more uncontrolled eating, suggesting a tendency towards habitual or dysregulated food-related behaviours.