The undertreatment of chronic pain and the prevention of drug abuse and diversion of pain medications (i.e., opioids) have been identified as public health issues in the United States. In this domain, the Drug Enforcement Administration (D.E.A.) faces challenges when enforcing the Controlled Substance Act because it is tasked with regulating the dispensing of opioids by physicians in the treatment of chronic pain, while also attempting to prevent their abuse and diversion. Thus, the D.E.A. must use discretion in how it enforces the C.S.A. because intentional actions to prevent opioid abuse and diversion could also unintentionally affect the willingness of primary care physicians to prescribe them in the treatment of chronic pain. As an initial step in clarifying the boundaries between the D.E.A. and the medical profession, it was necessary to assess physician perceptions about the D.E.A. 's use of enforcement discretion. A total of 205 Oregon primary care physicians completed a web-based survey examining three domains: concern about D.E.A. enforcement discretion; autonomy related to use of opioids in the treatment of chronic pain; and prescribing of opioids in the treatment of chronic pain. Results indicated that some physicians perceive a concern about D.E.A. enforcement discretion, and those who have concern are more likely to perceive having reduced autonomy related to the use of opioids in the treatment of chronic pain. The results do not support previous research that showed that such concerns directly affects physician prescribing of opioids. Instead, results reveal that concern about D.E.A. enforcement discretion is associated with reduced perceived autonomy, and reduced perceived autonomy is associated with less willingness to prescribe opioids in the treatment of chronic pain. This research takes the study on this topic one step further in identifying physician perceptions about D.E.A. enforcement discretion, and how these perceptions were associated with physician autonomy and prescribing of opioids in the treatment of chronic pain. In doing so, this research provides important scholarly contributions to the enforcement discretion literature, specific to the D.E.A., and medical professionalism as it pertains to physician autonomy related to the use of opioids in the treatment of chronic pain.

An increasing number of infants are diagnosed with neonatal abstinence syndrome (NAS) as a result of prenatal opioid exposure. Early intervention services are recommended for this population of children and families to mitigate developmental delays associated with NAS. The effectiveness of early intervention is dependent on the ability of interventionists who deliver these services. The purpose of this qualitative case study was to explore early interventionists' perspectives of self-efficacy when working with infants diagnosed with NAS and their families. Bandura's self-efficacy theory and Rotter's concept of locus of control provided the conceptual framework for this study. The study's guiding research questions focused on early interventionists' self-efficacy beliefs and factors that may affect those beliefs in their work with infants diagnosed with NAS and their families. Data were collected via semistructured interviews with 8 interventionists. Themes emerged from both in vivo and a priori coding pertaining to interventionists' self-efficacy beliefs working with the NAS population. Most interventionists in this study reported feeling highly efficacious in their work with infants with NAS and their families despite a lack of applicable educational and professional preparation. Interventionists attributed their professional efficacy to their own self-study, experience, and motivation to learn. Interventionists agreed that training specific to their work with NAS may improve their ability and self-efficacy in their work with infants with NAS and their families. Targeted training to increase interventionists' self-efficacy in their work with infants diagnosed with NAS and their families may result in increased effectiveness of intervention services and lead to lifelong positive outcomes for these vulnerable children.

Abuse of painkiller drugs and non-medical use of drugs among young adults continues to be a public health crisis in the United States. Living arrangements and source of treatment referral were considered as the social context that could contribute to increased admissions to treatment for drug abuse. The purpose of this study was to examine the relationship between, independent living arrangement, the principal source of referral, and abuse of opioid, heroin, and cocaine. Steered by the conceptual framework of the biopsychosocial model, this study used the data from the 2015 Treatment Episode Data Set: Admissions managed by the Substance Abuse and Mental Health Services Administration. Multiple logistic regression analyses were performed to test the hypotheses regarding a predictive relationship between independent living arrangement, the principal source of treatment referral, and admissions to treatment for abuse of opioid, heroin, and cocaine. The results showed a significant association between the source of treatment referrals and independent living arrangement, and the increased odds of admissions for prescription opioids use disorder, heroin use disorder, and cocaine use disorder among adults aged 18-34 living in the United States. The implication for positive social change included a need for a targeted treatment and other intervention programs for young adults' users with associated higher-risk treatment referral categories and exposed to neighborhoods factors and health-risk behaviors in reducing the crisis of drug abuse in the United States.

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The period of early life is important for the development of individual brain function and behavior. Human studies have shown altered vulnerability to develop psychopathology and/or excessive drug intake, possibly leading to dependence, as a consequence of early life experiences. In the present thesis, maternal separation (MS), an experimental model for studies of early environmental influences, was used to investigate long-term effects on neurochemistry, voluntary ethanol intake and exploration and risk assessment behavior in rats. Rat pups were assigned to one of three different rearing conditions: daily 15 min (MS15) or 360 min (MS360) of MS and normal animal facility rearing (AFR) during the first three weeks of life. Measurements of adult endogenous opioid peptide levels, opioid- and dopamine receptor density revealed minor MS-induced effects on the opioid system whereas interesting alterations were found in dopamine receptor density. Long-term effects on voluntary ethanol intake showed distinct MS-induced alterations in male Wistar and ethanol-preferring AA (Alko, Alcohol) rats. Female Wistar rats were unaffected, indicating sex differences in the effects of MS on ethanol intake. Male MS15 rats generally had a slower acquisition phase and a low subsequent ethanol intake whereas male MS360 rats had a high ethanol intake. MS15 is therefore suggested to protect against a high voluntary ethanol intake in male rats whereas MS360 may serve as a risk factor. The recently established concentric square field test indicated alterations in risk assessment as well as an increased exploratory drive and somewhat higher risk-taking behavior in adult MS360 rats, while minor effects were seen in MS15 rats. Altogether, these results demonstrate that environmental influences during the period of early life can have long-term effects on neurochemistry and behavior. Of special interest is the finding that MS altered the inherited high ethanol intake in adult ethanol-preferring AA rats.

Lifetime prevalence estimates of psychotropic medicine use as well as prevalence of DSM-IV prescription drug use disorders from the baseline investigation of the Early Developmental Stages of Psychopathology (EDSP) Study are presented. Use of prescription medication at some time in their life was reported by 27.4% of the respondents. Illicit use of prescription drugs, which means an intake without medical legitimation, was reported by 4.5% of the sample. The findings suggest that abuse of and dependence on prescription drugs, with most cases reporting polysubstance use, is quite rare in the 14- to 24-year-olds. DSM-IV abuse was more prevalent than dependence (0.5 vs. 0.3%). In general, women reported higher prevalence rates of prescription drug use, whereas men reported higher prevalence rates of prescription drug disorders. This result suggests that men have a higher risk to develop a substance-use-related disorder.

Drug dependence is a serious and increasing problem in our society, especially among adolescents. The use of the large variety of substances available can result in a range of physiological and psychological adverse effects on individuals and negative consequences on the society overall. Several different types of drugs induce neurotoxicological damages, which in turn can generate impairment in for example the reward system and affect cognitive parameters.  The drug gamma-hydroxybutyrate (GHB) is usually considered a harmless compound among abusers, but has now shown to be highly addictive. Furthermore, GHB can cause memory impairments in both humans and animals. On the contrary, growth hormone (GH) and its main mediator insulin-like growth factor 1 (IGF-1) have recently been suggested to improve memory and learning in several studies. The hormones exhibit certain neuroprotective capabilities and have also previously been demonstrated to reverse opioid induced apoptosis in hippocampal cells. These effects and the fact that GHB is shown to increase GH secretion, which attracted considerable attention among body builders, led us to initiate studies on GHB and its impact on relevant systems in the central nervous system (CNS). Thus, the main purpose of the present investigation was to elucidate some of the underlying mechanisms that could account for the effects exerted by GH and GHB in the CNS. We found that a) GH affects the density and functionality of GABAB-receptors and opioid receptors in the male rat brain, b) GHB induces cognitive deficits and down-regulates GABAB-receptors, c) GHB treatment creates an imbalance between the endogenous opioids Met-enkaphalin-Arg6Phe7 (MEAP) and dynorphin B and increases the levels of MEAP in regions of the brain that are associated with drug dependence, and d) GHB affects the expression of IGF-1 receptors but not the plasma levels of IGF-1. In conclusion, the present work demonstrates that GH interacts with both opioid and GABAB-receptors in the male rat CNS and that GHB has an impact on brain regions associated with cognition and the development of dependence. These observations may be of relevance in many aspects related to addiction and might be translated into humans.

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 30% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of injury, remains unclear. We have previously reported in rats that inflammation experienced on the day of birth permanently upregulates central opioid tone, resulting in a significant reduction in adult pain sensitivity. However, the impact on early life pain on anxiety- and stress-related behavior and HPA axis regulation is not known. Therefore the goal of this dissertation was to determine the long-term impact of a single neonatal inflammatory pain experience on adult anxiety- and stress-related responses. Neuroanatomical changes in stress-associated neurocircuits were also examined. As the endogenous pain control system and HPA axis are in a state of exaggerated developmental plasticity early in postnatal life, and these systems work in concert to respond to noxious or aversive stimuli, this dissertation research aimed to answer the following questions: (1) Does neonatal injury produce deficits in adult stress-related behavior and alter stress-related neuroanatomy through an opioid-dependent mechanism? (2) Does neonatal injury alter receptor systems regulating the activation and termination of the stress response in adulthood? (3) Are stress- and pain-related neurotransmitters altered within the first week following early life pain? (4) Is early activation of the pain system necessary for the long-term changes in anxiety- and stress-related behavior? Together these studies demonstrate the degree, severity and preventability of the long-term deficits in stress responding associated with a single painful experience early in life. The goal of this research is to promote change in the treatment of infant pain in the NICU to reduce long-term sensory and mental health complications associated with prematurity.