Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19.

Neurobiology of Addiction

New Challenges in Addiction Medicine: COVID-19 Infection in Patients With Alcohol and Substance Use Disorders-The Perfect Storm.

A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction.

Reinforcement history is a particularly potent predictor of future addictive behaviors. For the most part, researchers have studied the operant in order to understand and control positive reinforcement that maintains substance use behavior. However, negative reinforcement can be just as powerful in increasing the likelihood of substance use in the future, and some data suggest that negative (and not positive) reinforcement predicts increased difficulties associated with substance abuse over a person's lifetime. Negative reinforcement may be occurring if clients are avoiding withdrawal symptoms, escaping reality, self-medicating, or avoiding loss of friends. In such cases, therapists may wish to use strategies such as response prevention, generating alternative activities, environmental interventions within the family and community, and emotion regulation and distress tolerance skills. ********** Examining the function of substance use behavior is the foundation of credible psychosocial research and clinical practice concerning the prevention and treatment of addictive behaviors. Reinforcement history is a particularly potent predictor of future addictive behaviors. For the most part, researchers have studied the operant in order to understand and control positive reinforcement that maintains substance use behavior. The most obvious example of positive reinforcement concerns physical euphoria associated with drug use. The rewarding effects can be immediate and quite powerful, making it likely that the behavior will be repeated in the future. Furthermore, if the euphoria is not always predictable and occurs intermittently, then reduction or cessation of the substance use becomes even more difficult since intermittent positive reinforcement schedules tend to maintain persistent behavior in the absence of consistent access. However, negative reinforcement also can powerfully increase the likelihood of substance use in the future. Some research findings suggest that negative (and not positive) reinforcement may predict increased difficulties associated with substance abuse over a person's lifetime (e.g., Carey & Correia, 1997). People who abuse substances often make statements such as using makes me feel normal, which provide clues to the function of the behavior. The language implies that without the substance use the person feels abnormal, and that substance use takes away the aversive abnormality (hence, negative reinforcement). NEGATIVE REINFORCEMENT OF SUBSTANCE USE Negative reinforcement is understood to increase the likelihood that a behavior will be repeated in the future. A negative reinforcer strengthens behavior that reduces an aversive outcome (e.g., Skinner, 1974). Negative reinforcement of substance use means that an aversive outcome is reduced by the use of the substance, making it more likely that substance use behavior will occur again in the future. Substance use is often negatively reinforced on an intermittent schedule, making extinction of the behavior more difficult. Indeed, extinction of substance use does appear to be a difficult proposition, perhaps owing to the power of the intermittent reinforcement schedule. One function of problematic drug use may be to reduce aversive withdrawal symptoms. A coffee-drinking reader who has experienced the pain of a caffeine headache after a prolonged period without coffee may understand the function of drinking coffee to reduce the headache. For other more life threatening forms of addictive behaviors, one common question asked of people to determine the extent of a substance use problem is something like, do you use substances to reduce a hangover or stop the shakes? A positive response to such a question often suggests a greater constellation of consequences associated with problematic substance use (Buchsbaum, Buchanan, Centor, Schnoll, & Lawton, 1991; Dyson, et al., 1998). In the case of reduction of aversive withdrawal symptoms, negative reinforcement via substance use can be extraordinarily powerful. …

Alcohol use disorder (AUD) can be defined by a compulsion to seek and take alcohol, the loss of control in limiting intake, and the emergence of a negative emotional state when access to alcohol is prevented. Alcohol use disorder impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). Compulsive drug seeking that is associated with AUD can be derived from multiple neuroadaptations, but the thesis argued herein is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from the dysregulation of specific neurochemical elements that are involved in reward and stress within basal forebrain structures that involve the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include decreases in reward neurotransmission (e.g., decreases in dopamine and opioid peptide function in the ventral striatum) and the recruitment of brain stress systems (e.g., corticotropin-releasing factor [CRF]) in the extended amygdala, which contributes to hyperkatifeia and greater alcohol intake that is associated with dependence. Glucocorticoids and mineralocorticoids may play a role in sensitizing the extended amygdala CRF system. Other components of brain stress systems in the extended amygdala that may contribute to the negative motivational state of withdrawal include norepinephrine in the bed nucleus of the stria terminalis, dynorphin in the nucleus accumbens, hypocretin and vasopressin in the central nucleus of the amygdala, and neuroimmune modulation. Decreases in the activity of neuropeptide Y, nociception, endocannabinoids, and oxytocin in the extended amygdala may also contribute to hyperkatifeia that is associated with alcohol withdrawal. Such dysregulation of emotional processing may also significantly contribute to pain that is associated with alcohol withdrawal and negative urgency (i.e., impulsivity that is associated with hyperkatifeia during hyperkatifeia). Thus, an overactive brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of AUD. The combination of the loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement that at least partially drives the compulsivity of AUD.

Substance use disorders in pregnancy: clinical, ethical, and research imperatives of the opioid epidemic: a report of a joint workshop of the Society for Maternal-Fetal Medicine, American College of Obstetricians and Gynecologists, and American Society of Addiction Medicine

Alcohol Use Disorders and the Use of Treatment Services Among College-Age Young Adults

1. Ximena Sanchez-Samper, MD* 2. John R. Knight, MD* 1. *Center for Adolescent Substance Abuse Research, Children's Hospital Boston, Boston, Mass After completing this article, readers should be able to: 1. Discuss current trends in adolescent substance use and the specific substances used most commonly among 8th, 10th, and 12th graders. 2. Identify risk and protective factors, including genetic and environmental correlates, for the initiation of substance use in adolescents. 3. Discuss the most common concomitant mental health disorders and how they can affect the course of diagnosis and treatment for substance abuse. 4. Delineate the variety of treatment options available. 5. Describe the role of the pediatrician in educating patients and families on substance abuse prevention; performing screening and initial assessments; and providing support, brief counseling, or referrals for in-depth treatment. Adolescence is a time of physical, emotional, and psychological maturation as well as a period of searching for independence and experimentation. One area of experimentation associated with adolescence is substance use. (1) Although many adolescents experiment with drugs and alcohol from time to time without enduring problems, those who develop the disorders of substance abuse and dependence make substance use a major public health concern. The Monitoring the Future Study (MTFS) is a nationwide survey measuring smoking, drinking, and illicit drug use among nearly 50,000 8th, 10th, and 12th graders in more than 400 secondary schools in the United States each year. (2)(3) According to the 2006 overview of findings from the MTFS, approximately one fifth (21%) of today's 8th graders, more than one third (36%) of 10th graders, and nearly half (48%) of all 12th graders reported using an illicit drug at least once during their lifetimes. Despite a minimum legal age requirement to purchase alcohol, 6% of 8th graders, 19% of the 10th graders, and 30% of the 12th graders self-reported drunkenness during the month prior to being interviewed. (2)(3) Among the problems experienced by adolescents who use alcohol and drugs are …

Poster Abstracts from the AAAP 20th Annual Meeting and Symposium

Service Utilization Differences for Axis I Psychiatric and Substance Use Disorders Between White and Black Adults

The constructs of emotion and motivation are intimately linked. Throughout my career, W. Horsley Gantt and Joseph V. Brady laid a rich foundation for understanding the concept of emotion, derived from two prominent traditions of physiology and psychology: classical conditioning and operant conditioning, respectively. This framework guided my fierce interest in motivation in general and the interaction between reward and stress, which began at John Hopkins University with my thesis work under the mentorship of Zoltan Annau, with help from Solomon Synder and Joseph Brady, among many others. Using the study of the neurobiology of addiction as a framework, I argue that drug addiction can be heuristically framed as a cycle of three stages—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation (“craving”)—that involve domains of incentive salience/pathological habits (mediated by basal ganglia circuits), reward deficits/stress surfeit (mediated by extended amygdala circuits), and executive function deficits (mediated by the frontal cortex), respectively. Movement through the three stages involves a transition from positive reinforcement that is associated with the rewarding effects of drugs of abuse to another major source of reinforcement, specifically negative reinforcement that is driven by negative emotional states (termed the “dark side” of addiction). Repeated overstimulation of the reward systems with drugs of abuse decreases reward function, characterized by a decrease in brain stimulation reward and presumbably reflecting a dysphoria-like state. The construct of negative reinforcement, defined as drug taking that alleviates a negative emotional state that is created by drug abstinence, is particularly relevant as a driving force in both the withdrawal/negative affect and preoccupation/anticipation stages of the addiction cycle. From a neurobiological perspective, the negative emotional state that drives such negative reinforcement is hypothesized to derive from excessive activation of the brain reward systems that leads to a decrease in the function of normal reward-related neurocircuitry (dopamine, opioid peptides) in the ventral striatum and persistent recruitment of anti-reward systems, reflected by sensitization of the brain stress systems (corticotropin-releasing factor, dynorphin) within the extended amygdala. This shift in motivation is hypothesized to reflect the allostatic misregulation of hedonic tone such that drug taking makes the hedonic negative emotional state worse during the process of seeking temporary relief with compulsive drug taking. Understanding the neuroplasticity of the neurocircuitry that comprises negative reinforcement that is associated with addiction is a key to understanding motivation in general and its representation in pathophysiology.

Substance Abuse-Related Mortality Among Middle-Aged Male VA Psychiatric Patients

Substance use disorder (SUD) among women of reproductive age is a complex public health problem affecting a diverse spectrum of women and their families, with potential consequences across generations. The goals of this study were 1) to describe and compare the prevalence of patterns of injury requiring emergency department (ED) visits among SUD-positive and SUD-negative women and 2) among SUD-positive women, to investigate the association of specific categories of injury with type of substance used. This study was a secondary analysis of a large, multisource health care utilization data set developed to analyze SUD prevalence, and health and substance abuse treatment outcomes, for women of reproductive age in Massachusetts, 2002 through 2008. Sources for this linked data set included diagnostic codes for ED, inpatient, and outpatient stay discharges; SUD facility treatment records; and vital records for women and for their neonates. Injury data (ICD-9-CM E-codes) were available for 127,227 SUD-positive women. Almost two-thirds of SUD-positive women had any type of injury, compared to 44.8% of SUD-negative women. The mean (±SD) number of events also differed (2.27 ± 4.1 for SUD-positive women vs. 0.73 ± 1.3 for SUD-negative women, p < 0.0001). For four specific injury types, the proportion injured was almost double for SUD-positive women (49.3% vs 23.4%), and the mean (±SD) number of events was more than double (0.72 ± 0.9 vs. 0.26 ± 0.5, p < 0.0001). The numbers and proportions of motor vehicle incidents and falls were significantly higher in SUD-positive women (22.5% vs. 12.5% and 26.6% vs. 11.0%, respectively), but the greatest differences were in self-inflicted injury (11.5% vs. 0.8%; mean ± SD events = 0.19 ± 0.9 vs. 0.009 ± 0.2, p < 0.0001) and purposefully inflicted injury (11.5% vs 1.9%, mean ± SD events = 0.18 ± 0.1 vs. 0.02 ± 0.2, p < 0.0001). In each of the injury categories that we examined, injury rates among SUD-positive women were lowest for alcohol disorders only and highest for alcohol and drug disorders combined. Among 33,600 women identified as using opioids, 2,132 (6.3%) presented to the ED with overdose. Multiple overdose visits were common (mean ± SD = 3.67 ± 6.70 visits). After adjustment for sociodemographic characteristics, psychiatric history, and complex/chronic illness, SUD remained a significant risk factor for all types of injury, but for the suicide/self-inflicted injury category, psychiatric history was by far the stronger predictor. The presence of SUD increases the likelihood that women in the 15- to 49-year age group will present to the ED with injury. Conversely, women with injury may be more likely to be involved in alcohol abuse or other substance use. The high rates of injury that we identified among women with SUD suggest the utility of including a brief, validated screen for substance use as part of an ED injury treatment protocol and referring injured women for assessment and/or treatment when scores indicate the likelihood of SUD.

Substance Use Disorders Are Deadly.

Background: Unhealthy substance use is a growing public health issue. Intersections with the health care system offer an opportunity for intervention; however, recent estimates of prevalence for unhealthy substance use among all types of hospital inpatients are unknown. Methods: Universal screening for unhealthy alcohol or drug use was implemented across a 999-bed general hospital between January 1 and December 31, 2015. Nurses completed alcohol screening using the Alcohol Use Disorders Identification Test alcohol consumption questions (AUDIT-C) with a cutoff of ≥5 for moderate risk and ≥8 for high risk and drug screening using the single-item screening question with ≥1 episode of use considered positive. Results: Out of 35,288 unique inpatients, screens were completed on 21,519. There were 3,451 positive screens (16% of all completed screens), including 1,291 (6%) moderate risk and 1,111 (5%) high risk screens for alcohol and 1,657 (8%) positive screens for drug use. Among screens that were positive for moderate- or high-risk alcohol use, 221 (17%) and 297 (27%), respectively, were concurrently positive for drug use. The majority (61%) of patients with unhealthy alcohol use was on the medical services. Men, those who were white or Hispanic, middle-aged, single, unemployed, or screened positive for drug use were more likely to screen positive for high-risk alcohol use. Those who were younger, single, worked less than full time, or screened high risk for alcohol were more likely to screen positive for drug use. Discordance between diagnosis coding and screening results was noted: 29% of high-risk alcohol use screens had no alcohol diagnosis coding associated with that admission, and 51% of patients with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis code of alcohol dependence had AUDIT-C scores of <8. Conclusions: Across a general hospital, 16% of patients screened positive for unhealthy substance use, with the highest volume on medical floors. Nursing-led screening may offer an opportunity to identify and engage patients with unhealthy substance use during hospitalization.