Neural correlates of drinking reduction during a clinical trial of cognitive behavioral therapy for alcohol use disorder.

Background: Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and goal-directed behavior, plays a role in behavior change during CBT by facilitating the regulation of craving (ROC).

Methods: Treatment-seeking participants with AUD (N = 22) underwent functional magnetic resonance imaging (fMRI) scanning both before and after a 12-week, single-arm trial of CBT, using an ROC task that was previously shown to engage the DLPFC.

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder.

Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal.

Neural correlates of drinking reduction during cognitive behavioral therapy for alcohol use disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a brain region implicated in cognitive control and goal-directed behavior, plays a role behavior change during CBT by facilitating regulation of craving. To examine this, treatment-seeking participants with AUD (N=22) underwent functional MRI scanning both before and after a 12-week single-arm trial of CBT, using a regulation of craving (ROC) fMRI task designed to measure an individual's ability to control alcohol craving and previously shown to engage the DLPFC.

Drinking reduction during cognitive behavioral therapy for alcohol use disorder is associated with a reduction in anterior insula-bed nucleus of the stria terminalis resting-state functional connectivity.

Background: Connectivity between the anterior insula (AI) and the bed nucleus of the stria terminalis (BNST) may play a role in negative emotions that drive compulsive drinking in patients with alcohol use disorder (AUD). We hypothesized that reductions in drinking during cognitive behavioral therapy (CBT), an effective treatment that teaches regulation (coping) skills for managing negative emotions during abstinence, would be associated with reductions in resting-state functional connectivity (RSFC) between the AI and the BNST.

Methods: We included 18 patients with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of AUD who were (1) seeking treatment and (2) drinking heavily at baseline.

Open-label trial of a single-day induction onto buprenorphine extended-release injection for users of heroin and fentanyl.

Background And Objectives: Fentanyl and other highly potent synthetic opioids are the leading cause of opioid overdose deaths in the United States.

Methods: This study was an open-label, uncontrolled 12-week outpatient clinical trial to test the feasibility of a single-day induction onto extended-release buprenorphine (BXR) injection treatment for five adults (N = 5) with opioid use disorder using heroin-containing fentanyl. Participants were planned to receive three monthly BXR injections (300, 300, and 100 mg).

Case Series: Rapid Induction Onto Long Acting Buprenorphine Injection for High Potency Synthetic Opioid Users.

Background And Objectives: Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.

Methods: In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.

Cognitive Neuroscience Approaches to Understanding Behavior Change in Alcohol Use Disorder Treatments.

Researchers have begun to apply cognitive neuroscience concepts and methods to study behavior change mechanisms in alcohol use disorder (AUD) treatments. This review begins with an examination of the current state of treatment mechanisms research using clinical and social psychological approaches. It then summarizes what is currently understood about the pathophysiology of addiction from a cognitive neuroscience perspective.

Cognitive regulation of craving in alcohol-dependent and social drinkers.

Background: Helping alcohol-dependent individuals to cope with, or regulate, cue-induced craving using cognitive strategies is a therapeutic goal of cognitive behavioral therapy (CBT) for alcohol dependence. An assumption that underlies this approach is that alcohol dependence is associated with deficits in such cognitive regulation abilities. To date, however, the ability to utilize such strategies for regulation of craving has never been tested in a laboratory setting.

The insula: a critical neural substrate for craving and drug seeking under conflict and risk.

Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking-the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use.

The contributions of cognitive neuroscience and neuroimaging to understanding mechanisms of behavior change in addiction.

In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC.

The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making.

We have recently shown that damage to the insula leads to a profound disruption of addiction to cigarette smoking (Naqvi et al., Science 315:531-534, 2007). Yet, there is little understanding of why the insula should play such an important role in an addictive behavior.

The hidden island of addiction: the insula.

Most prior research on the neurobiology of addiction has focused on the role of subcortical systems, such as the amygdala, the ventral striatum and mesolimbic dopamine system, in promoting the motivation to seek drugs. Recent evidence indicates that a largely overlooked structure, the insula, plays a crucial part in conscious urges to take drugs. The insula has been highlighted as a region that integrates interoceptive (i.

Damage to the insula disrupts addiction to cigarette smoking.

A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not involving the insula to undergo a disruption of smoking addiction, characterized by the ability to quit smoking easily, immediately, without relapse, and without persistence of the urge to smoke. This result suggests that the insula is a critical neural substrate in the addiction to smoking.

Skin conductance responses are elicited by the airway sensory effects of puffs from cigarettes.

The airway sensations stimulated by smoking are an important source of hedonic impact (pleasure) for dependent smokers. The learning process by which these sensations become pleasurable is not well understood. The classical conditioning model predicts that airway sensory stimulation will elicit sympathetic arousal that is positively correlated with the hedonic impact that is elicited by airway sensory stimulation.

The airway sensory impact of nicotine contributes to the conditioned reinforcing effects of individual puffs from cigarettes.

Puffs from cigarettes are the fundamental unit of smoking reward. Here, we examined the extent to which reward from puffs can be derived from the airway sensory effect of nicotine, in the absence of a direct central nervous system effect of nicotine. We did this by assessing the self-reported reward obtained from individual puffs from nicotinized, denicotinized and unlit cigarettes within 7 s of inhalation, which is before nicotine had an opportunity to reach the brain.