Chong Kin Ngai. / Summary in Chinese. / Thesis (MBA) - Chinese University of Hong Kong. / Bibliography: l. 118-119.

Context Chronic pain and opioid dependence confer substantial individual and societal burdens and are notoriously difficult to treat effectively. Their comorbid presentation further complicates effective treatment through complex physiological and environmental interactions. Objectives (1) What are the clinical characteristics and treatment outcomes associated with comorbid chronic pain in ORT patients? (2) Does the patient-attributed direction of the causal relationship in the development of opioid dependence and chronic pain identify two clinically-distinct treatment populations? (3) What is the incidence of iatrogenic opioid dependence or abuse following opioid analgesic treatment? (4) Is there evidence of opioid-induced hyperalgesia in humans? Methods Primary data Participants were 467 treatment-seeking, opioid-dependent patients. Materials comprised standardised instruments – focusing on illicit substance use and mental health characteristics – completed by medical staff at study inception, and extracts of routinely-collected clinical datasets spanning the follow-up period. Procedures involved the use of a health informatics approach. Electronic linkage of data collected at study inception with routinely-collected clinical datasets spanning the 5-year follow-up period. Secondary data Systematic searches were undertaken using six electronic research databases, supplemented by manual searches. Study quality was assessed using instruments developed by NIH. Data synthesis using random effects models (DerSimonian-Laird method) generated: (1) a pooled incidence of iatrogenic dependence or abuse following opioid analgesic treatment; and (2) a pooled effect of opioid exposure on the development of opioid-induced hyperalgesia. Additional analyses included assessment of heterogeneity in study effects, within- and between-study risk of bias and sensitivity analyses. Results A total of 246 (53%) patients reported comorbid chronic pain. This ‘comorbid’ group was associated with increased mortality, physical and mental health problems, service utilisation and illicit drug use, specifically benzodiazepines and cannabinoids. Within the ‘comorbid’ group, patients who reported a causal impact of opioid dependence on the development of pain were associated with increased illicit drug use and psychiatric morbidity. Secondary data analyses revealed a 4.7% incidence estimate of iatrogenic dependence or abuse following opioid analgesic treatment, and evidence of the development of opioid-induced hyperalgesia following therapeutic opioid exposure. Conclusions Elevated mortality, morbidity and illicit drug use in opioid-dependent patients with comorbid chronic pain reflects a patient population with substantial health burdens. The dynamic relationship between these severe and chronic conditions necessitates complex, multimodal treatment strategies and multiagency collaboration, including general psychiatric intervention. Whilst a substantial proportion reported that opioid dependence developed as a consequence of pain problems, there is evidence to suggest that the assumed risk of iatrogenic opioid dependence and abuse may be an overestimate; however, therapeutic opioids may lead to other problems that impact on treatment effectiveness, such as opioid-induced hyperalgesia.

Opioids are the most effective treatment for pain, but a host of side effects such as lethal overdoses limits their use. Endomorphins are endogenous opioid ligands that show promise as a basis for safer analgesics. Several EM analogs were developed to provide equal analgesic effects compared to morphine, with reduced respiratory depression, motor, cognitive, tolerance, and reward side effects. Tested here in reward models, morphine was compulsively self-administered and produced conditioned place preference (CPP) and locomotor sensitization after repeated injections. In sharp contrast, EM analogs were inactive in all of these models. Mechanisms for reduced tolerance and reward are proposed here. Chronic EM analog infusions produced substantially less tolerance than equi-effective doses of morphine. Morphine upregulated glial cell markers of proinflammatory activation and signaling as well as the neuronal proinflammatory peptide CGRP. By contrast, EM analogs did not produce glial or CGRP activation suggesting reduced proinflammatory side effects. In the CPP reward model, morphine produced a place preference and decreased the cell soma size of dopamine (DA) neurons in the ventral tegmental area (VTA), a critical area for reward. EM analog 4 did not produce CPP and did not change the size of these neurons in the VTA. Penetration of the blood-brain barrier (BBB) by EM analogs was confirmed by central antagonism of the antinociceptive effects of peripherally administered analogs. This work suggests that EM analogs do not promote reward behaviors and do not produce morphological changes to DA neurons in the VTA, despite BBB penetration. Therefore, the reduced tolerance and reward side effects of the analogs could be due to lack of proinflammatory effects and reduced DA neuron alterations. Finally, the subjective effects of EM analogs were tested in a drug discrimination (DD) model. During DD test sessions, rats responded on the morphine-paired lever for food when pre-injected with EM analogs, indicating that the analogs were perceived as being more similar to morphine than vehicle, despite evidence that they did not produce rewarding effects. Data shown here suggest a dual role for EM analogs in the treatment of pain and opioid addiction. / 1 / Mark R. Nilges

Researchers have indicated that Internet addiction is a wide-spread problem, impacting the lives of an estimated 4-10% of all Internet users. Researchers have also indicated that Internet addiction has a social component, with Internet addicts using the Internet to build and maintain new social relationships at a much higher rate than non-addicts. This study explored Internet addiction in the context of Massively Multiplayer Online Role-Playing Games (MMORPGs). Data were drawn from MMORPG players and from mental health counselors to determine incidence rates of Internet addiction among MMORPG players, social needs that were predictive of Internet addiction, rates of treatment seeking behaviors by MMORPG players for Internet addiction, and how Internet addiction is diagnosed and treated by mental health counselors. For this study, the MMORPG Player Survey and the Counselor Survey were used to collect data from MMORPG players and mental health counselors. The MMORPG Player Survey was administered to 513 MMORPG players. The Counselor Survey was administered to 80 mental health counselors. Results from the MMORPG Player Survey indicated that approximately 15% (n=78) of MMORPG players met criteria for Internet addiction, as defined by the Diagnostic Questionnaire (DQ). A stepwise regression analysis of loneliness, confidence, liberation, validation, and support found that loneliness and confidence were both predictive of Internet addiction among participants (F2,473=115.921, p< .001) with an adjusted R square of .326. Of MMORPG players surveyed, .6% (n=3) indicated that they have sought professional help for Internet addiction. Mental health counselors reported that Internet addiction was most likely to be diagnosed as depression, obsessive-compulsive disorder, or impulse control disorder. Furthermore, mental health counselors reported that they were most likely to treat Internet addiction using one of the following theoretical orientations: cognitive, reality, family systems, or solution focused. These findings highlight a subpopulation of the online community who are in need of mental health services and are not receiving them. Recommendations for future research include qualitative studies of the social aspects of MMORPG gaming among Internet addicts, as well as research exploring potential deterrents to mental health services among this population.

Whereas clinical professionals and the general public recognize exercise in moderate amounts as an important component of a healthy lifestyle, researchers have noted that when taken to an excessive level, exercise may become addictive. Usually considered rare in the broad exercising population, risk for exercise addiction has been found to be more prominent among certain specialized groups, such as runners. This study investigated the risk for exercise addiction in a unique group of endurance athletes-Sprint-, Olympic-, Half-Ironman, and Ironman-distance triathletes. The sample consisted of 1285 male and female triathletes, ranging in age from 18 to 70 years old, recruited through the electronic newsletter of a national triathlon organization. During the past year participants completed at least one triathlon of Sprint-, Olympic-, Half-Ironman-, and/or Ironman-distance, or were in training for one. To measure the risk for exercise addiction, participants completed an online questionnaire, comprising the six items of the Exercise Addiction Inventory (Terry, Szabo, & Griffiths, 2004), six items added by the investigator, and a demographics section. Results indicate that approximately 20% of triathletes are at risk for exercise addiction, 79% are committed exercisers who exhibit some symptoms of exercise addiction, and 1% are asymptomatic. Results also demonstrate that female triathletes are at greater risk for exercise addiction than male triathletes. Training for longer distance races (e.g., Olympic-, Half-Ironman-, and Ironman-) put triathletes at greater risk for exercise addiction than training for shorter races. No significant association exists between the risk for exercise addiction and either the number of years of participating in the sport or the length of training sessions. However, as the number of weekly training hours or the number of weekly training sessions increases, so does a triathlete's risk for exercise addiction. Results demonstrate that triathletes have a lower than anticipated risk for exercise addiction, yet a higher risk than the general exercising population. Because at-risk triathletes need greater clinical attention, further research should be conducted to help clinicians develop enhanced awareness and appropriate interventions.

Up to 65% of individuals with a spinal cord injury (SCI) experience neuropathic pain, and cite this as one of the most significant consequences of injury. Opiate analgesics are one of the most effective, but also most concerning, treatments for neuropathic pain. In fact, the use of morphine after SCI can potentiate the development of paradoxical pain symptoms, and continuous administration can lead to dependence, tolerance, and addiction. Empirical evidence suggests that the addictive potential of morphine decreases when used to treat neuropathic pain, but this has not been studied in an SCI model. These studies, therefore, aimed to investigate the addictive potential of morphine in a rodent model of spinal contusion injury. These experiments used a conditioned place preference (CPP) paradigm to examine whether subjects with SCI would develop a preference in the acute phase of injury, and whether a place preference would be expressed after the development of neuropathic pain symptoms in the chronic phase of injury. Results suggest that the time of treatment did affect the development of a preference for the morphine-paired context; subjects displayed a CPP in the acute, but not the chronic phase of SCI. In addition, the findings indicate that spinal neurons are sufficient, but not necessary, for producing a morphine-induced place preference. Overall, the results suggest that morphine could be used for the clinical treatment of neuropathic pain without concerns of addiction. Although SCI alone did not reduce the addictive potential of morphine in the acute phase of injury, the lack of preference in the chronic phase suggests that addiction may be reduced by molecular changes that accompany the development of neuropathic pain. Moreover, we hypothesize that the analgesic effects of morphine acting on spinal and peripheral mu-opioid receptors (MOR's) underlies the development of CPP in the acute phase of injury. This hypothesis is supported by the CPP established with intrathecal morphine administration. Nonetheless, the current studies cannot discount the role of supraspinally-mediated reward in the development of place preference after injury. Further work is needed to distinguish between the addictive and analgesic properties of morphine.

Therapeutic communities provide structure, support and a safe living environment for individuals attempting to recover from addiction. Using peer influence, counseling, education, self-help groups, and case management, they assist residents in conforming to social norms and developing effective coping mechanisms while remaining drug-free. Prior studies have consistently demonstrated the effectiveness of these programs. But, why are they effective for some and not others? This study explored the residents1 backgrounds and the methods employed by them to assimilate into the therapeutic community, the recovering community, and then society at large. The data confirmed my suspicion that the women's ability to conform to social norms and develop effective coping mechanisms was dependent upon the level of attachment to prosocial others they attained while in a therapeutic community. The rules and requirements of Flower House are designed to promote prosocial attachments and conformity to social norms. Face-to-face interviews were conducted with 15 past and present residents of Flower House, a therapeutic community for substance-abusing women and their children. These women volunteered to participate.

Few studies have examined the social process of drug abuse recovery. To determine how recovering addicts use reference agents, such as reference groups and/or reference others, to achieve and maintain sobriety within the context of the Narcotics Anonymous (NA) support group experience, this study examines how Newcomers learn the norms and values associated with NA, how Newcomers become integrated into the NA group and internalize acceptable recovery behaviors, and how Newcomers transition to becoming Oldtimers. In this study, participant observation and in-depth, semi-structured interviewing (N = 13) based upon convenience sampling were employed. This study elicited six stages of social referencing that Newcomers experience during the process of becoming recovering addicts.

The researcher investigated the relationship between anger experience and expression, coping styles, and expectancies regarding the effects of alcohol in a young male population. Anger experience and expression was measured using the State-Trait Anger Expression Inventory, coping styles were assessed using the Coping Response Inventory, alcohol expectancies were determined using the Alcohol Effects Questionnaire-2, and alcohol use was measured using the Alcohol Use Inventory. The results indicated that young males who abuse alcohol utilize less effective coping styles, such as cognitive avoidance. Alcohol abusing males also believe alcohol will increase their power and aggression. A linear regression demonstrated that males who abuse alcohol experience and express more anger than males who do not abuse alcohol. The analysis further revealed that experience and expression of anger was related to the poor coping styles and expectancies regarding the effects of alcohol for males who abuse alcohol.

Recent national surveys have demonstrated an increase in alcohol use among adolescents over the past five years (Johnston, O'Malley, & Bachman, 2003; Kann et al., 2000). It is important to understand factors that influence alcohol use in order to aid in the creation of preventative measures due to the many possible negative consequences associated with drinking alcohol (i.e., unwanted sexual activity, delinquency, abuse of other drugs, violence, car accidents, and poor academic performance) (Boyd, Howard, & Zucker, 1995). Two factors that have been studied as possible predictors of adult and adolescent alcohol use are personality and pubertal onset. Specifically, studies have linked the personality factors of Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism and reports of alcohol use in adults and older adolescents (Austin et al., 2003; Gullone & Moore, 2000; Kubicka, Matejcek, Dytrych, & Roth, 2001; Markey, Markey, & Tinsley, 2003; Musgrave-Marquart & Bromley, 1997). Furthermore, studies have also found that the age at which one reaches puberty has been linked to participation in risky behaviors, specifically alcohol use (Felson & Haynie, 2002; Ge, Conger, & Elder, 2001; Graber, Lewinsohn, Seeley, & Brooks-Gunn, 1997; Sonis, Comit, & Blue, 1985; Stice, Presnell, & Bearman, 2001). The current study examined the personality factors of Extraversion, Openness to Experience, and Conscientiousness, pubertal onset, and alcohol usage (underaged drinking and intoxication). One hundred boys in the sixth, seventh, and eighth grades and their parents were randomly selected to serve as participants in the study. The boys completed the Self-Rating Scale for Pubertal Development (Carskadon & Acebo, 1993), Adolescent Risk Behavior Questionnaire (Gullone & Moore, 2000), and a revised version of the NEO-Five Factor Inventory (Costa & McCrae, 1992). It was hypothesized the three personality factors of Conscientiousness, Extraversion, and Openness to Experience would significantly predict the level of alcohol usage in boys. Specifically, lower scores on the Conscientiousness Scale, higher scores on the Extraversion, and higher scores on the Openness scales would be predictors of underaged drinking and intoxication in boys. Second, it was hypothesized that the level of pubertal development would significantly predict of alcohol involvement. More specifically, higher scores on the Pubertal Development Scale would significantly predict underaged drinking and intoxication in boys. Finally, it was expected that scores obtained from the Conscientiousness, Extraversion, and Openness scales would interact with scores obtained on the Pubertal Development Scale and significantly predict underaged drinking and intoxication. Standard regressions were conducted to examine the hypotheses. Results of the regression analysis indicated that the overall model (pubertal development) significantly predicted underaged drinking and intoxication, but accounted for only 10% variance in underaged drinking and 13% in intoxication.