Prescription opioid abuse in the United States is an alarming health issue. In 2015, approximately 2 million people abused prescription opioids, and 12 million individuals misused their prescription opioid pain relievers. The percentage of individuals who died as a result of opiate abuse increased from 22% in 2013 to 76% in 2014. The purpose of this project was to evaluate the influence of an inner-city drug treatment (DTBF) program on opioid users' behavior. The practice question addressed whether knowledge of signs and symptoms of opioid withdrawal obtained from the DTBF program resulted in a significant behavioral change in opioid use in 45 adults ages 18 to 25. The Centers for Disease Control and Prevention framework for program evaluation was used to guide the study. Data were collected using a pretest and posttest with the Clinical Opiate Withdrawal Scale (COWS) over a 6-month period. Results of t-test analysis indicated a significant change in drug use (p = .000). Recommendations to clinic administrators included encouraging all staff to use the COWS in screening individuals and observing them at each clinic visit. The implication of this study for social change is that findings may be used to reduce drug abuse and misuse among prescription opioid users.

Opioid overdoses are increasing and several efforts are being made to reduce this problem. One potential solution is overdose education and naloxone distribution. Project ASSERT began distributing naloxone in conjunction with its overdose education program in 2009. Project ASSERT’s overdose education and naloxone distribution program trained opioid users in recognition, risk factors, and response to overdoses, as well as how to use nasal naloxone kits. Opioid users that had received overdose education only were compared with those that received overdose education and naloxone kits. The goal was to determine if there were any differences in occurrence of nonfatal overdoses, overdose response, illicit opioid use, and opioid agonist treatment. This retrospective study involved phone-surveying patients from a hospital billing list. It was obtained through Project ASSERT and contained the names of patients that had received overdose education only or overdose education and naloxone distribution from January 2011 to February 2012. Questions were asked about the respondents’ naloxone kits, overdose history since their Project ASSERT visit, response to the last witnessed overdose, 30-day substance use, and overdose risk knowledge. Chi-square tests were used to compare the groups. 51 out of 415 eligible were successfully surveyed from March 2012 to October 2012. The surveys occurred on average 11.8 months after their Project ASSERT visit. 73% (37) had naloxone kits and most kept them where they lived (12). There were 9 successful overdose reversals reported. 76% (39) of the respondents did not overdose in the intervening period. There was no statistical difference between the two groups in overdose occurrence, 19% trained with naloxone versus 29% trained without naloxone (p=0.45). 16 out of 19 (84%) of the naloxone group properly responded to an overdose, whereas 3 out of 8 (38%) of those trained without naloxone properly responded (p=.03). There was no statistical difference in illicit opioid use (p=1.0) and opioid agonist treatment (p=.53), 36% of the group trained with naloxone versus 35% of the group trained without naloxone, and 49% of those trained with naloxone versus 36% of those trained without naloxone, respectively. In studying the association between overdose education only and overdose education and naloxone distribution, it was found that there is not an increase in overdose and illicit opioid use. There also is no reduction in seeking for opioid agonist treatment. However, it was found that having naloxone kits does increase proper response to overdose. This is a promising result that could have an impact in reducing opioid overdose deaths.

Background: Opioid use disorder (OUD) has been an increasing concern in Canada as mortality rates continue to rise. Though OUD treatments, such as methadone maintenance treatment (MMT), reduce its burden, they could potentially cause harm due to OUD’s variance in severity and presentation across individuals. It is hypothesized that genetic variants such as single nucleotide polymorphisms (SNPs) could predispose patients to respond differently to MMT. In addition, sex differences have been observed in opioid use patterns, treatment outcomes, and genetic make-up. As such, this thesis aims to identify significant SNPs associated with treatment outcomes in genome-wide association studies, and test biologically relevant SNPs with MMT outcomes of interest, while highlighting sex differences. This is achieved through a systematic review protocol, a systematic review, and a candidate gene study. Methods: A protocol was prepared for the planning of the first ever systematic review of genome-wide significant findings of medication-assisted treatment outcomes for OUD patients. The systematic review assessed the literature findings and study qualities, narratively summarizing significant associations. Next, a candidate gene study analyzed the association between SNPs in OPRM1 and CYP2B6 genes, and continued opioid use, relapse, and methadone dose within an ancestrally European sample (n=1226). Sex-stratified and sex-interaction analyses were also conducted. Results: The systematic review included 5 studies and qualitatively assessed 43 unique genetic variants. The candidate gene study showed no significant associations between the selected OPRM1 and CYP2B6 SNPs and outcomes of interest. While no significant differences between the sexes were observed, rs73568641 and rs3745274 showed near significance associations in only one sex, females, and males, respectively. Discussion: Through the study of genetic variants associated with treatment outcomes in the literature and our sample of ancestrally European individuals on MMT, we were able to highlight gaps in pharmacogenetics research and identify areas of focus for future studies. / Thesis / Master of Science (MSc) / Recently, opioid use disorder (OUD) has been declared a national crisis in Canada. OUD treatments are helpful in reducing opioid use and adverse events. However, their dosing and metabolism in patients can impact continued opioid use, relapse, or treatment dose changes. Due to the variability in response between individuals, there might be a genetic basis to treatment outcomes. This thesis explores which genetic variants reported in previous studies are involved in OUD treatment outcomes. Then, it tests select genetic variants in OPRM1 and CYP2B6 genes to see if they are linked to specific outcomes in an Ontario population and tries to identify if these associations differ by sex. No significant associations were found, though associations in males and females had near-significant results in one sex but not the other. Despite suggesting sex’s possible involvement in treatment outcomes, more research is necessary to confirm these findings.

An abundance of literature has shown the five-factor model personality traits can influence current and lifetime substance use. Life satisfaction, although less clearly, has also demonstrated a significant contribution to substance use behaviors and outcomes. Still, little is known about how life satisfaction influences the relationship between personality and substance use measures pertinent to recovery like drug use refusal self-efficacy. The goal of this study is to advance the current literature on substance use by examining the mechanisms influencing the relationship between personality and life satisfaction and drug use refusal self-efficacy for a sample diagnosed with at least one substance use disorder (SUD) and/or alcohol use disorder (AUD). Data was analyzed using deidentified information from a large diverse SUD client pool (n = 348) who were recruited from the general population and from two Midwest SUD treatment centers for a larger parent study. A series of mediation and moderation analyses were tested. The relationships between both neuroticism and conscientiousness with drug use refusal self-efficacy were significantly mediated by life satisfaction. Life satisfaction significantly moderated the relationship between extraversion and drug use refusal self-efficacy. These findings suggest life satisfaction may be a novel modifiable treatment target to reduce negative effects of personality on SUD drug refusal self-efficacy, and that life satisfaction may influence and change how extraversion relates to risks among those in recovery. / M.S. / Substance misuse costs the United States healthcare system billions each year, but substance use disorder treatment reduces these costs. Unfortunately, only a small percentage of individuals seek treatment in part because it is notoriously difficult, and relapses are common. Factors like personality traits and life satisfaction influence current and lifetime substance use. The goal of this study was to advance the current literature on substance use by examining the mechanisms influencing the relationship between personality and life satisfaction and the ability for an individual to refuse drugs or alcohol (drug use refusal self-efficacy). Data was analyzed using information from a large diverse substance use disorder client pool (n = 348) who were recruited from the general population from two Midwest treatment centers. A series of mediation and moderation analyses were tested. Life satisfaction influenced the relationships between both neuroticism and conscientiousness with drug use refusal self-efficacy. The relationship between extraversion and drug use refusal self-efficacy differed based on the individual’s life satisfaction. These findings suggest modifying life satisfaction may reduce negative effects of personality on drug refusal self-efficacy, and that life satisfaction may influence and change how extraversion relates to risks among those in recovery.

No description available.

Chronic opioid exposure in utero places the infant at risk of Neonatal Abstinence Syndrome (NAS), a clinical diagnosis of neurological, autonomic, and/or gastrointestinal withdrawal symptoms from opioid abstinence at birth. The prevalence of NAS is rising concurrently with the recent epidemic of opioid misuse among the general population in the United States, including pregnant women. Opioid misusing women typically receive methadone or buprenorphine as a treatment throughout pregnancy. However, the opioid misuse during pregnancy is associated with higher obstetric complications and a higher incidence of NAS in infants, at times requiring pharmacological intervention. The exact consequences to the human development from opioid exposure in utero remain unclear. Animal studies suggest that the fetal impacts of opioid exposure may differ from the consequences for an adult who uses opioids. Furthermore, there may be neurodevelopmental alterations in myelin physiology, dendritic length in the brain, and neurotransmitter systems when a child is exposed to opioids in utero. Clinical studies highlight associations between perinatal opioid exposure and gene mutation variants, cranial abnormalities on imaging, and a high prevalence of ocular and visual comorbidities. Ocular and visual comorbidities are of particular interest, because they may be treatable when detected early. The current literature about NAS infants and ocular and visual comorbidities is limited by the retrospective and small case-control study designs employed by the majority of the research groups. The proposed study design is a prospective study comparing groups of opioid exposed and non-opioid exposed infants born at Boston Medical Center in Boston, Massachusetts. The ocular and visual comorbidities detected in each group will be quantified, while analyzing the relationship and the relative risk attributable to the infant’s and mother’s demographics. The social context of opioid misuse may complicate the interpretation of the data; however, the design anticipates sufficient recruitment and generalizability as it is conducted at a safety net hospital. Ultimately, the goal of this proposal is to reduce the risk to the fetus with perinatal opioid exposure and build the knowledge base about ocular comorbidities in NAS infants so that optimal and comprehensive care can be provided in the future.

Women in Central Appalachia represent a significant proportion of those engaging in problematic patterns of opioid use, which is concerning given the limited available services in the region and gender specific treatment barriers. This investigation seeks to understand the role of mental health and substance use symptoms among incarcerated Central Appalachian women and build on the conceptual model of substance use treatment utilization purposed by Leukefeld and colleagues (1998). Data for this study was drawn from a larger longitudinal investigation (NIDA 1R01-DA033866) and baseline data collected during initial interviews was analyzed. The sample included 400 women incarcerated at one of three central Appalachian jails. Bivariate analyses determined significant relationships between symptoms of depression, anxiety, trauma and substance use. Binary logistic regression was used to assess the factors influencing treatment utilization. The overall multivariate model of treatment utilization with eight factors (income, overdose history, injection drug use, entered detox, attended self-help groups, substance use problems, number of children, and no way to get to their provider) significantly improved the prediction of treatment utilization. Implications of this study highlight the importance of continued interventions at the individual, community, and policy level.

Background: The UK has a high prevalence of opioid use; although this population is ageing. The use of opioids is associated with excess mortality and offending and so remains a priority for public health and criminal justice policy. Aims: There are two broad aims for this thesis: firstly, to quantify excess mortality and offending associated with opioid use, and secondly, to assess the effectiveness of drug treatment at reducing these harms. Methods: Cohorts were extracted from the Drug Data Warehouse (DDW); a collection of case-linked drug treatment and criminal justice datasets, linked to mortality and offending records. Excess mortality was quantified by comparing deaths observed in a cohort of opioid users to that expected from the general population, matched on age and gender. The association between opioid use and offending was quantified using a cohort of drug-tested offenders, comparing those who tested positive for opiates and/or cocaine with those who tested negative. The effectiveness of treatment was calculated using two separate measures: the effect of being in treatment, using a time-dependent treatment exposure, and the effect of initiation to treatment. In the latter analysis, the approach was to use observational data to emulate randomised controlled trials, in an attempt to better establish the causal effect of treatment initiation. Confounding bias, when treatment exposure is time-dependent, was discussed, using path diagrams and simulations. Results: The opioid-user cohort extracted from the DDW is the largest assembled to-date (N = 198,247). Controlling for age and gender, opioid use was associated with considerably higher mortality and offending than non-users. Older age was a risk factor for drug related poisoning (DRP) death. The association with offending was considerably higher for females. Compared to periods out of treatment, the risk of a fatal DRP was lower during pharmacological treatment but not during periods where the user received psychological support only. Simulations illustrated that when treatment exposure is time-dependent, analyses may be biased in the presence of confounding by a time-dependent variable. Among opioid-using offenders, there was little support for the hypothesis that initiation to drug treatment was effective at reducing the risk of future acquisitive offending. Conclusion: In England and Wales, there remain considerable excess mortality and offending associated with opioid use. Age and gender have an important influence on these relationships. Treatment (as delivered in England and Wales) appears effective at reducing the risk of a drug-related death, provided there is a pharmacological component, but not at reducing the risk of future offending.

Opioid use disorder is a chronic, relapsing disease, with more than 85% of individuals experiencing a relapse episode within one year. One common reason patients relapse is due to intense cravings, which are defined as the compulsive urge to use the drug. In fact, craving was recently added to the DSM criteria for substance use disorder diagnosis. Counterintuitively, cravings intensify over the course of extended abstinence, especially in response to drug-paired cues, a phenomenon known as “incubation of craving”. This contributes to difficulty in maintaining long-term sobriety. The mesocorticolimbic reward pathway facilitates self-administration and cue-induced incubation of craving for drugs of abuse and natural rewards, such as sucrose. In particular, the shell sub-region of the nucleus accumbens is a critical brain region involved in context/cue-mediated reward seeking. In the experiments described here, we utilized an incubation of craving model, in which male and female rats self-administered opioids (morphine or heroin) or sucrose for 10 days. Sucrose served as an important control for delineating drug-induced changes from those caused in response to natural rewards, which are not the intended target of potential treatments. Reward delivery was paired with a cue light that was later used to elicit craving. After self-administration, rats underwent brief (one day) or extended (30 days) forced abstinence. One or 30 days later, they were returned to the chambers for a “cue test”, in which responses on the previously reward-associated lever triggered cue presentation, but no contingent reward. We used this model to further delineate behavioral and affective changes that accompany increased opioid craving in late abstinence, as well as molecular alterations underlying craving in rats that did not undergo a cue test. We found an opioid-specific behavioral signature in which peak opioid craving is accompanied by decreased grooming and hyperactivity in both sexes. We tracked the female estrous cycle throughout, as these fluctuations in reproductive hormones (akin to the menstrual cycle) are shown to affect cocaine- and nicotine-related behaviors. We found no differences between females in different phases of the estrous cycle in terms of self-administration, nor craving. RNA sequencing of the nucleus accumbens shell revealed robust changes in gene expression that occurred across extended abstinence, though the genes themselves were altered in a sex- and reinforcer-specific manner. In general, we found many behavioral and molecular changes that were unique to sex and reinforcer (sucrose versus opioids). This is promising in terms of identifying opioid-specific targets that are unlikely to affect the natural reward system in both sexes. Changes in gene expression in the brain are mediated in part by epigenetic processes that influence access of transcriptional machinery to DNA. Acetylation of histone tails, the proteins around which DNA is wrapped and packaged in the nucleus, have been identified as permissive marks that facilitate long-lasting changes in transcriptomics in response to environmental insults. Opioids promote increased acetylation, which may contribute to some of the reported changes here. We tested the efficacy of JQ1, a treatment that interferes with the read-out of opioid-induced acetylated marks, at attenuating heroin self-administration. When administered as an intracerebroventricular microinjection on self-administration day 11, JQ1 had no effect on subsequent heroin taking in either sex, suggesting that it may not be suitable as a systemic treatment at the dose given. These studies lay the groundwork for future studies to administer other treatments throughout abstinence, based on the opioid-specific genes and pathways identified here, to reduce cue-induced heroin craving and the accompanying suite of behaviors in males and females. / Psychology

Opioid misuse and addiction constitute a significant public health challenge in the 21st century, with opioids involved in the majority of drug overdose deaths since 1999. A vigorously researched area that contributes substantially to the opioid misuse and addiction challenge is pain. The impact of pain, however, on important health outcomes for individuals in recovery from opioid use is less well understood. The effects of pain on substance use and mental health outcomes was investigated among individuals in recovery from opioid use disorder. Two studies are reported. First, the relationships between pain status and severity on substance use, treatment utilization, and mental health outcomes (e.g., depressive symptoms) was characterized cross-sectionally. Second, subgroups of OUD recovery defined by depression, opioid withdrawal, and pain were identified. Relationships between recovery subgroups, OUD symptoms, remission, opioid use, and quality of life were assessed. Finally, transitions among subgroups across 4 years of recovery were characterized. The present findings support pain as a key dimension of opioid use disorder recovery, highlighting the distinction between acute and chronic pain, the dynamic nature of opioid use disorder recovery, and emphasizing the necessity of integrating pain into opioid use disorder treatment. / Doctor of Philosophy / Misuse of and addiction to opioids is a significant health challenge. Pain has played a central role in facilitating the opioid epidemic in the United States, but the impact of pain on substance use and mental health outcomes for individuals in recovery from opioid use is less well understood. The following two studies investigated how pain affects substance use and mental health outcomes among individuals in recovery from opioid use disorder. Study 1 examined how different types of pain (chronic pain, acute pain, no pain) affect substance use, treatment use, and mental health measures (e.g., depression, quality of life). Study 2 investigated the role that depression, opioid withdrawal, and pain have in defining different groups in opioid recovery. Together these studies support pain as an important factor in OUD recovery, highlight the distinction between acute and chronic pain, emphasize the importance of integrating treatment for opioid use disorder and pain, and demonstrate that opioid use disorder recovery is a dynamic process with individuals transitioning among different recovery groups over time.