The Cognitive Impact Of Opioids During Chronic Administration
Funder
National Health and Medical Research Council
Funding Amount
$416,024.00
Summary
Many people are now being prescribed opioid drugs for long periods of time, mainly for the treatment of chronic pain. These drugs can adversely affect the person's ability to drive a car, hold down a job, and perform normal functions of daily living. This project will investigate what types of impairment are produced by these drugs and how the drugs can best be used so as to minimise the effects on patients.
Novel Delta Receptor Expression In Opioid Tolerant/dependent Neurons
Funder
National Health and Medical Research Council
Funding Amount
$370,350.00
Summary
Opioids such as morphine and heroin act on specific molecular targets, or receptors, in the brain. Long term use of opioids produce changes in brain receptor systems that greatly diminish the effects of these drugs (tolerance), as well as producing an adverse withdrawal syndrome on cessation of use (physical dependence). The present proposal will identify the mechanisms of adaptations in cellular function in nerve cells critical for these changes. In particular, we have identified enhanced sensi ....Opioids such as morphine and heroin act on specific molecular targets, or receptors, in the brain. Long term use of opioids produce changes in brain receptor systems that greatly diminish the effects of these drugs (tolerance), as well as producing an adverse withdrawal syndrome on cessation of use (physical dependence). The present proposal will identify the mechanisms of adaptations in cellular function in nerve cells critical for these changes. In particular, we have identified enhanced sensitivity of receptor, the delta receptor, that is closely related to the opioid receptor but is not a target for heroin or morphine. We will identify the mechanisms of enhanced activity of this receptor after chronic use of morphine with a view to tergeting therapeutics to manage tolerance and physical dependence in opioid addicts and chronic pain patients.Read moreRead less
Contextual Control Over Relapse To Drug Seeking: Behavioural And Neural Mechanisms.
Funder
National Health and Medical Research Council
Funding Amount
$395,750.00
Summary
Drug addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. Prolonged drug use is associated with increased rates of physical problems (e.g., cardiovascular disease), mental health problems (e.g., depression and anxiety), and criminal involvement (e.g., property crimes and incarceration). A defining feature of drug addiction is that it is a chronically relapsing condition. Between ....Drug addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. Prolonged drug use is associated with increased rates of physical problems (e.g., cardiovascular disease), mental health problems (e.g., depression and anxiety), and criminal involvement (e.g., property crimes and incarceration). A defining feature of drug addiction is that it is a chronically relapsing condition. Between 60-80% of addicts attempting to give up drug taking will relapse to drug taking. The behavioural and brain mechanisms which underpin this persistent propensity to relapse are largely unknown. This project studies the behavioural and brain mechanisms for relapse to drug addiction. This project uses a well validated animal model of drug taking to ask why relapse occurs. It will identify some of the environmental antecedents to relapse and the brain mechanisms which mediate relapse. As such, this project will project will provide important information about relapse to drug addiction and may help identify targets for therapeutic intervention and possibly disrupt the addictive cycle.Read moreRead less
Drug addiction is a major health and societal problem in Australia. Relapse is among the most fundamental problems for addicts. This project studies the behavioural and brain mechanisms for relapse to drug seeking. It studies why relapse is more likely in some places than others; the brain mechanisms for this contextual control over relapse; and how relapse to seeking drug rewards is similar to and different from relapse to seeking non-drug rewards.
Increased Vulnerability To Stress During Opiate Dependence: Molecular, Anatomical, And Behavioural Correlates
Funder
National Health and Medical Research Council
Funding Amount
$272,640.00
Summary
Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, s ....Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, stress increases the pleasurable effects of heroin and stress increases the aversive effects of heroin withdrawal. These effects will encourage addiction and discourage addicts from seeking treatment. Stress can also cause an otherwise drug-free individual to relapse to heroin addiction despite having been drug-free for some time. In this project we will study why stress has such a large impact on heroin addicts and heroin addiction. We will test the hypothesis that heroin use actually produces profound alterations in the neural network in the brain which controls responses to stress. This project uses a simple animal model of heroin addiction whereby rats are injected with morphine to study the regulation of several genes which are important in responding to stress. We will also study how this exposure and changes in gene expression alter neurobiological, cardiovascular, and behavioural responses to stress. This project will identify parts of the brain that are altered during heroin addiction, and will also identify why heroin addicts are more vulnerable to stress than the general population. Therefore, this project will help us to identify targets for therapeutic intervention (both psychological and pharmacological) and possibly disrupt the addictive cycle.Read moreRead less
The Role Of Anhedonia In Recovery From Opiate Addiction
Funder
National Health and Medical Research Council
Funding Amount
$541,022.00
Summary
There is growing evidence that changes occur within the addicted brain reducing a drug user's ability to experience everyday pleasures. In this study, we will examine how a drug user's ability to experience pleasure relates to relapse and recovery. We will conduct a series of tests on a large sample of recently abstinent heroin addicts and follow them for 12 months. This project will provide unique insights that will be of direct relevance to clinical treatment.
Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, is known to be preferentially taken up into fat tissue where it can be stored for weeks, months and possibly years. Boy fat has the capacity to store large quantities of THC and the slow passive release of THC from fat cells into the blood accounts for why THC remains at detectable levels in the blood or urine for weeks after exposure to cannabis. Under n ....Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, is known to be preferentially taken up into fat tissue where it can be stored for weeks, months and possibly years. Boy fat has the capacity to store large quantities of THC and the slow passive release of THC from fat cells into the blood accounts for why THC remains at detectable levels in the blood or urine for weeks after exposure to cannabis. Under normal conditions the slow passive release of THC from fat cells has negligible effects on the user as the amounts involved are so small. However, we have recent preliminary evidence to show that conditions associated with increased fat metabolism (e.g. dieting, exercise or stress) cause a greatly enhanced release of THC from fat stores into the blood supply. Further, we have demonstrated that such levels attained promote significant behavioural and physiological changes The current proposal aims to further characterise this phenomenon. We aim to: (1) determine the length of time that THC can be stored in fat before being released into blood, (2) establish that the release of THC stored in fat tissue may be promoted by fat breakdown associated with food deprivation, stress or exercise, (3) characterise the physiological and behavioural effects of THC released from fat, (4) determine the mechanisms responsible for THC release from fat, and (5) determine if THC released from fat can cross from the bloodstream into saliva. This proposal has far reaching consequences for our understanding of the long-term effects on cannabis use on physical health and behaviour. Further, it may have major implications for the correct interpretation of analytical data from road-side saliva testing and forensic and criminal cases involving cannabis use.Read moreRead less
Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitiv ....Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Mechanisms Of Endogenous Cannabinoid Mediated Analgesia Within The Midbrain
Funder
National Health and Medical Research Council
Funding Amount
$518,820.00
Summary
While opioid analgesics such as morphine are the most important drugs used to treat moderate to severe pain, their usefulness is limited by side effects such as tolerance and respiratory depression. In addition, clinically relevant neuropathic chronic pain syndromes (caused by nervous system damage) are relatively resistant to opioids. Animal studies have shown that the active ingredient of the plant Cannabis sativa, THC, and a number of synthetic cannabinoids are analgesic in acute pain models, ....While opioid analgesics such as morphine are the most important drugs used to treat moderate to severe pain, their usefulness is limited by side effects such as tolerance and respiratory depression. In addition, clinically relevant neuropathic chronic pain syndromes (caused by nervous system damage) are relatively resistant to opioids. Animal studies have shown that the active ingredient of the plant Cannabis sativa, THC, and a number of synthetic cannabinoids are analgesic in acute pain models, and interestingly, in chronic neuropathic pain models. Unfortunately, cannabinoid also produce a spectrum of adverse side-effects. Administered cannabinoids such as THC produce their physiological effects by mimicking the actions of the body's own cannabinoids (endocannabinoids) by activating cell-surface proteins, called cannabinoid receptors. The endocannabinoid neurotransmitter system is emerging as a potential therapeutic target. For example, it has recently been shown that analgesia induced by physiological stressors is partly mediated by endocannabinoids within the brain. In addition, novel endocannabinoid breakdown inhibitors have some efficacy in animal models of anxiety and chronic pain. Several brain regions are known to play a pivotal role in the analgesic actions of exogenous and endogenous cannabinoids. In previous studies I have identified the cellular mechanisms by which exogenously applied opioids and cannabinoids produce their analgesic effects in single brain cells. However, the mechanisms of endocannabinoid actions within these brain regions are unknown. The proposed study will determine the cellular actions of endogenously released cannabinoids in normal animals and in chronic pain states. Parallel studies will examine the effect of modulation of the endocannabinoid system in animal models of pain. These techniques have the potential to identify novel endocannabinoid analgesic pharmacotherapies with enhanced efficacy and reduced side effects.Read moreRead less
What Triggers Complex Regional Pain Syndrome After Minor Injury?
Funder
National Health and Medical Research Council
Funding Amount
$958,898.00
Summary
Most people recover from minor trauma but some develop very disabling, difficult to treat, costly pain syndromes. We can identify those at high risk of developing such a syndrome after wrist fracture. By comparing inflammation, immune system function, stress, brain function and behaviour between high and low risk patients, we will take a major step towards understanding, preventing and treating these syndromes.