An investigation into the effects of methadone on cognitive and psychomotor function, mood, concentration and craving.

Methadone is a synthetic opioid that produces cross-tolerance with opiate drugs and can therefore be used to suppress withdrawal symptoms in opiate dependent patients. Methadone is the main treatment offered by the NHS in the UK for opiate dependence. Methadone can be used for both detoxification (if the primary treatment aim is abstinence from opiates), or as a maintenance dose (if the primary treatment aim is harm reduction until the patient is ready to detoxify). In the UK the number of deaths from methadone exceeds the number of deaths from heroin and numbers have increased over the last ten years.(ONS England and Wales: 1993-1997, 220 to 368 deaths from methadone, 55 to 169 deaths from heroin. Curran et.al. (1999) found no sedative, cognitive or psychomotor effects but an increase in craving for opiates in methadone maintenance outpatients, with a 33% increase in their prescribed maintenance dose of methadone. Previous studies have methodological limitations (Zacny, 1995, Weinreib et al, 1993) and inconclusive results. The aim of this study is to investigate the cognitive, psychomotor and mood effects of a 100% increase in methadone dose for opiate dependent in-patients, using a double blind, placebo controlled design, with urinalysis to address some limitations of previous research. A range of measures was used to assess the effects of this increase on cognitive and psychomotor functioning, mood and craving. On admission, participants were stabilised on methadone for 5 days, before the dose is reduced for detoxification in the usual way. Participants were assessed on day 3 and day 5. All participants received their complete dose each day, half the participants received methadone as one whole dose. The others received methadone in a divided dose (50% in the morning, 50% in the evening). The design was balanced for treatment order. Methadone vehicle (linctus) was used as a placebo to maintain double-blind conditions, resulting in the same quantity of linctus administered on each occasion. Both placebo and methadone were flavoured with peppermint so appeared, tasted and smelled the same. Participants were unable to distinguish methadone from placebo. There was no evidence of illicit drug use detected by urinalysis. Results suggest that Methadone has no effect on craving for heroin or mood, but significantly affects delayed recall. The implications of these findings for the treatment of opiate dependency are discussed

Heroin treatment - new alternative: proceedings of a seminar held on 1 November 1991, Ian Wark Theatre, Backer House, Canberra

"So our objective today is to explore the medical, health, social and law enforcement implications of evaluating, in the ACT, new approaches to the treatment of heroin dependent individuals. Drug policy is a highly political issue, any action to change the way we manage drug dependent people in the ACT has political implications for the ACT and for other parts of Australia as well. So I am delighted that we have representatives from drug and law enforcement agencies from most states of Australia here today and that many of the people who will frame attitudes to the proposed ACT trial will have an opportunity to discuss these issues in an open and uninhibited way.at more length later, would involve thoroughly examining the logistic feasibility of the proposed trial. If it was found to be logistically feasible, the third stage would be a small pilot study and only if that was found to work would a trial be conducted." - from Opening Address, Bob Douglas, Director, National Centre for Epidemiology and Population HealthAustralian National University, Australian Institute of Criminology, National Drug & Alcohol Research Centre; National Centre for Epidemiology and Population Healt

Heroin Treatment - New Alternative : proceedings of a seminar held on 1 November 1991, Ian Wark Theatre, Backer House, Canberra

The meeting today grows out of a study conducted jointly by the National Centre for Epidemiology and Population Health and the Australian Institute of Criminology in the early part of this year. That study was prompted by an invitation from the Chairman of the ACT Legislative Assembly’s Select Committee on HIV, Illegal Drugs and Prostitution - Mr Michael Moore - who invited us to examine the feasibility of a trial of the controlled availability of opioids in the ACT. Dr Gabriele Bammer, who directed that investigation, will be setting the scene for us by describing its conclusions at the outset of the day’s discussions. We hope that from that baseline we can move forward in the course of the day to explore the implications of those conclusions and to discuss whether or not it is appropriate to extend the feasibility study to the next stage. So our objective today is to explore the medical, health, social and law enforcement implications of evaluating, in the ACT, new approaches to the treatment of heroin dependent individuals. Drug policy is a highly political issue, any action to change the way we manage drug dependent people in the ACT has political implications for the ACT and for other parts of Australia as well. So I am delighted that we have representatives from drug and law enforcement agencies from most states of Australia here today and that many of the people who will frame attitudes to the proposed ACT trial will have an opportunity to discuss these issues in an open and uninhibited way.The meeting has been assisted by a grant from the ACT Government

The relation of socioeconomic and cognitive variables to dropout from a Salvation Army Drug Rehabilitation program

A group of 134 substance abusers from two Salvation Army Rehabilitation programs: the CDIP (Chemical Dependency Intervention Program) and the CDRP (Chemical Dependency Rehabilitation Program) were administered at intake to the program a demographic form, the CMRS (Circumstances, Motivation, Readiness and Suitability Scales), the Novaco Provocation Inventory (NPI) and the Cognitive Triad Inventory (CTI). A stepwise hierarchical analysis for each treatment was used to test the hypothesis asserts that the addition of cognitive factors would improve the prediction rate of dropout using demographic variables alone. Results supported this for the CDIP, but not the CDRP. The second hypothesis was that clients in the program would have elevated levels of NPI and CTI scores as compared to a normative population, which was confirmed by study. The third hypothesis that anger provocability as measured by the NPI would be correlated with the CTI was not supported

The role of emotions and physiological arousal in modulating impulsive behaviour.

Impulsivity received considerable attention in the context of drug misuse and certain neuropsychiatric conditions. Because of its great health and well-being importance, it is crucial to understand factors which modulate impulsive behaviour. As a growing body of literature indicates the role of emotional and physiological states in guiding our actions and decisions, we argue that current affective state and physiological arousal exert a significant influence on behavioural impulsivity. As 'impulsivity' is a heterogeneous concept, in this paper, we review key theories of the topic and summarise information about distinct impulsivity subtypes and their methods of assessment, pointing out to the differences between the various components of the construct. Moreover, we review existing literature on the relationship between emotional states, arousal and impulsive behaviour and suggest directions for future research

Behavioural and cellular basis of the vulnerability to develop compulsive heroin seeking habits

Addiction is a chronic relapsing disorder for which there is no effective treatment. This may reflect our lack of understanding of the psychological and neural mechanisms that support the transition, in vulnerable individuals, from recreational drug use to compulsive drug seeking habits. Over the last decade clinical and preclinical studies have begun to shed light on the psychological and neural basis of the individual vulnerability to cocaine addiction, but despite the epidemic in opiates addiction in the USA and incremental opioid drug abuse and addiction in the UK, heroin addiction has hitherto been under-investigated. Using a novel preclinical model of compulsive heroin seeking behaviour in which some rats self-administering heroin persist in responding under a second-order schedule of reinforcement despite punishment (Chapter 3), the experiments in this thesis investigated the psychological, behavioural, neural and cellular mechanisms involved in the vulnerability to develop compulsive heroin seeking. Chapter 4 aimed to identify behavioural traits, such as anxiety, stress reactivity or decision making, that predict an increased vulnerability to develop compulsive heroin seeking. Chapter 5 aimed to characterise the neural and cellular correlates of heroin seeking habits, and compulsivity. Based on the combination of hotspot analysis, quantitative PCR, RNAscope and western-blot analyses, the data presented demonstrate that compulsive habits are associated with a differential pattern of cellular plasticity within corticostriatal networks, and are preceded by diverse cellular adaptations, especially in the striatum, in vulnerable individuals. Finally, chapter 6 further investigated the cellular specificity of the observed adaptations in experiments that revealed exposure to heroin and cocaine, triggers a downregulation of the dopamine transporter preferentially in astrocytes, and not in neurons as previously thought. The results presented in this thesis offer new insights into the neural and cellular basis of the vulnerability to develop compulsive heroin seeking, a key feature of opioid addiction.Cambridge Commonwealth, European & International Trus

What are the impacts when primary care providers diminish stigma for patients with opioid use disorder in British Columbia?

Stigma is a complex phenomenon with a myriad of detrimental health and social impacts that are not fully studied or understood. Persistent stigma exists towards individuals who have opioid use disorder (OUD) in British Columbia. OUD is a chronic, relapsing, clinical condition that has been identified as one of the most challenging substance use disorders. For those affected, they must also endure the consequences of stigma that promote barriers to health care, health and social inequalities, diminished quality of life as well as increased morbidity and mortality. The current unremitting opioid overdose crisis in British Columbia further emphasizes the importance of eradicating stigma towards individuals who use opioids and/or suffer from OUD, as untreated OUD is fueling this multifaceted public health emergency. For these reasons, an integrative literature review has been conducted to identify how primary care providers in British Columbia can address the intersecting stigmas for individuals suffering OUD. The results are discussed within the context of primary health care in British Columbia. Whittemore and Knafl’s approach to the integrative literature review was utilized in this study to review eleven pertinent articles. The findings suggest that stigma occurs on varying levels for individuals with OUD that serve to reinforce each other and manifest as discrimination, mistrust, social distancing, minimized advocacy, unequal access to health care and suboptimal health care. Further, the findings indicated that the role of primary care providers may be instrumental in eradicating stigma in a timely manner. Recommendations for primary care providers to dismantle the stigma associated with OUD are discussed, and specific strategies for the primary care setting are presented.Opioid use disorderStigmaDiscriminationPrimary health carePrimary care provide

Substance-specific modulation of the affective and neurobiological effects of heroin and cocaine in human addicts

This dissertation investigates how the settings of drug use influence the affective and neurobiological response to heroin versus cocaine in addicts. Chapter 1 reviews the neuropharmacology of heroin and cocaine and the theoretical background for drugs-settings interactions, including a detailed discussion of findings from previous studies in animals and humans that show how the same settings can influence in opposite directions the reinforcing effect of heroin and cocaine. Cocaine self-administration, for example, was greatly facilitated when rats were tested outside the home environment relative to rats test at home. The opposite pattern was found for heroin. Translational studies in humans yielded similar results. Indeed, heroin and cocaine co-abusers reported using the two drugs in distinct settings: heroin preferentially at home and cocaine preferentially outside the home. The aim of this dissertation is to determine whether the setting could also influence in opposite manner the affective and neurobiological response to heroin and cocaine in human addicts. Chapter 2 illustrates the findings of a study aimed at testing the hypothesis that the affective state experienced under cocaine or heroin is the result of an interaction between central and peripheral drug effects and the surroundings of drug use. According to this hypothesis, when cocaine is taken at home there is a mismatch between the familiar environment and the peripheral effects such as arousal, increased heart rate, increased respiratory rate, and increased muscular tension (which are usually produced in stressful situations). This mismatch dampens cocaine-rewarding effects. A mismatch would also occurs when heroin (which produces sedation and decreases heart rate, respiratory rate, and muscular tension) is used outside the home in contexts requiring vigilance. We found indeed that co-abusers subjectively experienced opposite changes in arousal, heart rate, respiratory rate, and muscular tension in response to cocaine (increase) versus heroin (decrease). Most important, using a novel two-dimensional visual test, we found that in agreement with the working hypothesis the valence of the affective state produced by heroin and cocaine shifted in opposite directions as a function of the setting of drug use: heroin was reported to be more pleasant at home than outside the home, and vice versa for cocaine. Chapter 3 illustrates the results of in which emotional imagery was combined with fMRI to investigation the neurobiological underpinnings of drug and setting interactions in addicts. Heroin and cocaine co-abusers were asked to recreate real-world settings of drug use during fMRI. In agreement with the working hypothesis, we found that heroin and cocaine imagery produced opposite changes in BOLD in the prefrontal cortex and in the striatum, regions implicated in brain reward in humans. Furthermore the same pattern of dissociation was observed in the cerebellum, suggesting that that a fronto-triatal-cerebellar network is implicated in processing drug-setting interactions. Chapter 4 includes a summary of the results, a general discussion, and suggestions for future research and implication. The major finding is that the environment surrounding drug use can influence in opposite manner the affective and neurobiological response to heroin and cocaine, suggesting that therapeutic approaches to the treatment of drug addiction should take into account the distinctive effects of different classes of drugs as well as the contexts of drug use. The Appendix includes reprints of two papers reporting on additional studies conducted during the course of the Ph.D. program, which are not directly germane to the aims of the dissertation. Other three papers are in the pre-submission stage