Faculty Bibliography

BACKGROUND: Although attention deficit/hyperactive disorder (ADHD) is a common comorbidity in individuals who are diagnosed with substance use disorder (SUD), little data currently exist on the utility of screening tools in large samples of adults with SUD in inpatient treatment and the prevalence of ADHD in this population. The aims of this study were to assess the screen positive rate on the Adult ADHD Self Report Scale (ASRS) v.1.1 Screener in a large sample of adults being treated for SUD in a residential treatment facility (RTF) and to establish the imputed prevalence of adult ADHD. METHODS: Adults with SUD who were either newly admitted (abstinent for < 1 week) or in treatment in the RTF (abstinent < 3 months) were administered the ASRS v.1.1 Screener. Adults who screened positive on the ASRS v1.1 Screener (>or= 4/6 significant items) were then administered the Adult Clinician Diagnostic Scale (ACDS) v.1.2 to establish a diagnosis of ADHD and the positive predictive value (PPV) in this population. The imputed prevalence of adult ADHD was calculated based on the known rate of ADHD in the screened positive cohort and a calculated rate of ADHD in the screened negative sample based on prior studies of the ASRS v1.1 Screener in community-based and managed care samples. RESULTS: 1064 adults were screened via the ASRS v.1.1 Screener, with 92 screening positive (8.6% had >or= 4 significant items present). Fifty-three of those who screened positive were diagnosed as having adult ADHD (PPV = 57.6%). The imputed prevalence of adult ADHD in this population was 7.5%. CONCLUSIONS: The PPV for the ASRS v1.1 Screener for adult ADHD in this sample of adults with SUD was similar to that observed in a prior study of a managed care sample, but was somewhat less than that observed in the community-based sample. The imputed prevalence rate for comorbid ADHD in this study of adults with SUD in a RTF was similar to, but slightly lower than the prevalence rate of ADHD in patients with any SUD observed in the community-based sample

Substance use disorders are highly prevalent in the United States and cause considerable damage to our society. They are underrecognized and undertreated despite a vast body of literature demonstrating the efficacy of treatment using both psychosocial and psychopharmacological modalities. For the last decade, research and progress into the biological basis of the addictive process has led to a rapidly growing number of pharmacological agents used to interrupt the addictive process at its various stages such as the initiation of substance abuse, the transition from abuse to dependence, and the prevention of drug reinstatement or relapse. Food and Drug Administration-approved medications exist for nicotine, alcohol, and opioid use disorders, and progress is being made to develop agents for stimulant use disorders. Regarding nicotine use disorders, nicotine replacement therapies,bupropion and varenicline, have Food and Drug Administration approval, and future options exist with endocannabinoid antagonists and immune therapy. Aversive agents, opiate antagonists, and glutamate based interventions are currently approved to treat alcohol use disorders with future promise with GABAergic, serotonergic, and endocannabinoid system agents. Opiate addiction is treated by approved agonist and antagonist mu-opioid medications with the future potential for agents that can modulate the stress systems and the iboga alkaloids. Although no pharmacotherapies are currently approved for cocaine addiction, promising lines of research include agents that affect dopaminergic, GABAergic, serotonergic,and glutamatergic systems as well as the promise for immune therapies

Addiction is increasingly understood as a neurobiological illness where repetitive substance abuse corrupts the normal circuitry of rewarding and adaptive behaviors causing drug-induced neuroplastic changes. The addictive process can be examined by looking at the biological basis of substance initiation to the progression of substance abuse to dependence to the enduring risk of relapse. Critical neurotransmitters and neurocircuits underlie the pathological changes at each of these stages. Enhanced dopamine transmission in the nucleus accumbens is part of the common pathway for the positively rewarding aspects of drugs of abuse and for initiation of the addictive process. F-Aminobutyric acid,opioid peptides, serotonin, acetylcholine, the endocannabinoids, and glutamate systems also play a role in the initial addictive process. Dopamine also plays a key role in conditioned responses to drugs of abuse, and addiction is now recognized as a disease of pathological learning and memory. In the path from substance abuse to addiction, the neurochemistry shifts from a dopamine-based behavioral system to a predominantly glutamate-based one marked by dysregulated glutamate transmission from the prefrontal cortex to the nucleus accumbens in relation to drug versus biologically oriented stimuli. This is a core part of the executive dysfunction now understood as one of the hallmark features of addiction that also includes impaired decision making and impulse dysregulation.Understanding the neurobiology of the addictive process allows for a theoretical psychopharmacological approach to treating addictive disorders,one that takes into account biological interventions aimed at particular stages of the illness

Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify gene variants associated with heroin addiction in African Americans. The emphasis was on genes involved in reward modulation, behavioral control, cognitive function, signal transduction and stress response. We have performed a case-control association analysis by screening with 1350 variants of 130 genes. The sample consisted of 202 former severe heroin addicts in methadone treatment and 167 healthy controls with no history of drug abuse. Single nucleotide polymorphism (SNP), haplotype and multi-SNP genotype pattern analyses were performed. Seventeen SNPs showed point-wise significant association with heroin addiction (nominal P< 0.01). These SNPs are from genes encoding several receptors: adrenergic (ADRA1A), arginine vasopressin (AVPR1A), cholinergic (CHRM2), dopamine (DRD1), GABA-A (GABRB3), glutamate (GRIN2A) and serotonin (HTR3A) as well as alcohol dehydrogenase (ADH7), glutamic acid decarboxylase (GAD1 and GAD2), the nucleoside transporter (SLC29A1) and diazepam-binding inhibitor (DBI). The most significant result of the analyses was obtained for the GRIN2A haplotype G-A-T (rs4587976-rs1071502-rs1366076) with protective effect (P(uncorrected) = 9.6E- 05, P(corrected) = 0.058). This study corroborates several reported associations with alcohol and drug addiction as well as other related disorders and extends the list of variants that may affect the development of heroin addiction. Further studies will be necessary to replicate these associations and to elucidate the roles of these variants in drug addiction vulnerability.

The coming decades will see exciting breakthroughs in the treatment of SUDs, such as further elucidation of the genetic mechanisms of addiction. Yet if the past is any guide to the future, each new discovery will bring with it new challenges to the core ethical obligations of honoring informed consent, protecting confidentiality, and respecting justice, while also protecting the public from harm and ensuring the good of the individual patient. For the emerging scientific shift to a biobehavioral model of addiction to transform cultural attitudes and enhance treatment and research will require the scientifically rigorous and ethically sound agency of ethicists and addiction professionals to influence public policy. The growing body of neurobiologic evidence that contests traditional assumptions about free will and responsibility will evoke more deliberate and nuanced approaches to informed consent and treatment participation and dispute the forensic orientation in drug policy. If this unprecedented paradigm change can influence health care decision making in a reasoned and balanced fashion, there is real hope that the cultural stigma, which has warranted highly stringent confidentiality protections, and the disenfranchisement underlying health disparities in addiction treatment may move in the direction of compassionate and competent care for all those who suffer from addiction.

OBJECTIVES: This report focused upon the availability of infection-related health services in substance abuse treatment programs with and without addiction services tailored for special populations (women and non-white populations). METHODS: In a cross-sectional, descriptive design, treatment program administrators across the United States within the National Drug Abuse Treatment Clinical Trials Network provided information on program characteristics, the availability of infection-related services (four medical services and three non-medical services for HIV, HCV, and STI), and barriers to providing infection-related services. RESULTS: Of 319 programs, 269 submitted surveys (84% response rate). Of these, 80% provided addiction services for special populations. Programs providing addiction services designed for at least one special population, were more likely to provide infection-related health services, especially HIV-related education (94% versus 85%, p = 0.05) and patient counseling (76% versus 60%, p = 0.03) and were more likely to include outpatient addiction services (86% versus 57%, p<0.001) and outreach and support services (92% versus 70%, p=0.01). Barriers to providing infection-related services included funding (cited by 48.3% to 74.7% of programs), health insurance (cited by 28.9% to 60.8% of programs), and patient acceptance (cited by 23.2% to 54.3% of programs). CONCLUSIONS: Despite many barriers, infection-related healthcare is available in programs with addiction treatment services tailored for special populations, especially for African Americans and Latino Americans. Tailoring substance abuse treatment along with reducing barriers to infection-related care represent public health interventions with potential to reduce the burdens and disparities associated with these infections

Findings from neuroscience research hold promise for improved treatments for and prevention of substance use disorders (SUD), but ethical concerns about psychopharmacological research involving SUD may potentially undermine scientific progress. This article reviews the literature pertaining to seven ethical requirements that elucidate a coherent framework for evaluating the ethics of clinical SUD research protocols. Those requirements are social or scientific value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, informed consent, and respect for potential or enrolled subjects. An evidence-based analysis suggests that sound pharmacological research in SUD can safeguard the welfare of research participants while collecting valuable scientific data and benefiting society.

RATIONALE: Previous studies have suggested that chronic food restriction (FR) increases sensitivity of a neural substrate for drug reward. The neuroanatomical site(s) of key neuroadaptations may include nucleus accumbens (NAc) where changes in D-1 dopamine (DA) receptor-mediated cell signaling and gene expression have been documented. OBJECTIVES: The purpose of the present study was to begin bridging the behavioral and tissue studies by microinjecting drugs directly into NAc medial shell and assessing behavioral effects in free-feeding and FR subjects. MATERIALS AND METHODS: Rats were implanted with microinjection cannulae in NAc medial shell and a subset were implanted with a stimulating electrode in lateral hypothalamus. Reward-potentiating effects of the D-1 DA receptor agonist, SKF-82958, AMPAR antagonist, DNXQ, and polyamine GluR1 antagonist, 1-na spermine, were assessed using the curve-shift method of self-stimulation testing. Motor-activating effects of SKF-82958 were also assessed. RESULTS: SKF-82958 (2.0 and 5.0 mug) produced greater reward-potentiating and motor-activating effects in FR than ad libitum fed (AL) rats. DNQX (1.0 mug) and 1-na spermine (1.0 and 2.5 mug) selectively decreased the x-axis intercept of rate-frequency curves in FR subjects, reflecting increased responding for previously subthreshold stimulation. CONCLUSIONS: Results suggest that FR may facilitate reward-directed behavior via multiple neuroadaptations in NAc medial shell including upregulation of D-1 DA receptor function involved in the selection and expression of goal-directed behavior, and increased GluR1-mediated activation of cells that inhibit nonreinforced responses

Substance Abusers have a large number of medical and psychiatric problems, and 70-90% are smokers. The aim of this analysis was to examine the prevalence and correlates of medical and psychiatric problems in this sample of drug dependent patients who were participants in a multi-site study of smoking cessation interventions while engaged in substance abuse treatment. Descriptive analyses showed at baseline, 72.8% of participants had at least one medical problem and 64.1% had at least one psychiatric diagnosis. Medical problems correlated strongly with age, smoking severity, and pack-years; Psychiatric problems correlated with gender and ethnicity. Smoking cessation treatment was associated with a moderate reduction in the ASI Medical composite score. More research is needed on the possible effects of combined treatment of substance abuse and concurrent medical and psychiatric problems. Offering smoking cessation in conjunction with primary care may be a way to address the health needs of this population.