Glutamate - Adenosine Interactions And Drug-seeking
Funder
National Health and Medical Research Council
Funding Amount
$558,046.00
Summary
Substance abuse is a significant social and economic burdern upon Australian societies and on societies around the world. Treatment remains problematic due to the multi-layer nature of the disease, difficulties with treatment compliance and less than ideal treatment regimes. The present study aims to improve treatments for alcohol and drug abuse using a polypharmacy or multiple therapy approach, using pre-clinical models to determine the utility of this approach.
Ecstasy use is growing faster throughout the world than than any other drug of abuse. United Nations figures from 2003 show that it is used by more individuals than the combined total of cocaine and heroin users. Australia has the highest per capita use of 'Ecstasy' in the world with rates twice those of North Americal and Europe. As a result of this we also have a high rate of adverse effects. These can be immediate, and lead to death, or long term leading to brain damage and psychopathologies. ....Ecstasy use is growing faster throughout the world than than any other drug of abuse. United Nations figures from 2003 show that it is used by more individuals than the combined total of cocaine and heroin users. Australia has the highest per capita use of 'Ecstasy' in the world with rates twice those of North Americal and Europe. As a result of this we also have a high rate of adverse effects. These can be immediate, and lead to death, or long term leading to brain damage and psychopathologies. So far, no studies have been conducted,anywhere in the world, which have objectively examined the medical effects of 'ecstasy' in the dance clubs where it is used. Because of this, there is a lot of speculation on whether the animal based or hospital based studies are valid and relate to normal recreational use of this drug. This has led to a degree of suspicion by users and health professionals as to the medical problems claimed to be associated with the drug. This project extends a pilot study we undertook which has highlighted that in a recreational setting it is likely that specific individuals are susceptible to damage by 'ecstasy'. The purpose of this project is to examine this in detail, and identify who, and why some young persons are at risk of immediate life threatening outcomes from 'ecstasy' use or may develop brain damage later. The intended outcome is to provide clear evidence of adverse effects and why they occur. This evidence may be used to improve harm minimisation and treatment programs.Read moreRead less
A Controlled Trial Of An Opportunistic Intervention To Reduce Suicide Risk Among Alcohol And Other Substance Misusers
Funder
National Health and Medical Research Council
Funding Amount
$361,000.00
Summary
Hopelessness, depression and suicidal ideation are common among people who misuse alcohol and other substances. A general relationship between alcohol-substance abuse and self-harming - suicidal behaviour has been recognised for decades. From the point of view of diagnosed substance abusers there is a correspondingly high incidence of suicide and self-harm. The lifetime risk for suicide in alcohol dependence is higher than for schizophrenia or affective disorder. Despite the public health and pe ....Hopelessness, depression and suicidal ideation are common among people who misuse alcohol and other substances. A general relationship between alcohol-substance abuse and self-harming - suicidal behaviour has been recognised for decades. From the point of view of diagnosed substance abusers there is a correspondingly high incidence of suicide and self-harm. The lifetime risk for suicide in alcohol dependence is higher than for schizophrenia or affective disorder. Despite the public health and personal burden associated with suicidality, the general lack of skills and focus on management of self-harm in specialised drug and alcohol services is of great concern. In this study, all patients attending drug and alcohol services will be screened for suicide risk, and offered a comprehensive psychological treatment to reduce suicide risk and the use of alcohol and other substances.Read moreRead less
Brain Pathways Underlying Vulnerability To Drug Relapse
Funder
National Health and Medical Research Council
Funding Amount
$416,788.00
Summary
Addiction to drugs is a major health and social burden for Australian society. Once addiction is established, prevention of relapse is the most significant obstacle to successful treatment. Unfortunately, efficacious pharmaceutical options to treat relapse are lacking. By employing an animal model of relapse that accurately reflects drug taking in humans the proposed project aims to advance our understanding of the brain mechanism underlying addiction.
Diversion And Misuse Of Stimulant Medication For ADHD Among Illicit Psychostimulant Users
Funder
National Health and Medical Research Council
Funding Amount
$152,534.00
Summary
The practices of diversion and misuse of pharmaceutical stimulants give serious cause for concern due to their potential to increase the risk of drug toxicity, dependence, and serious adverse health consequences. These practices may be particularly harmful among illicit psychostimulant users. This will be the first to study the nature of diversion and misuse of pharmaceutical stimulants among illicit psychostimulant users and the first to examine the associated correlates and consequences.
The use of ecstasy and similar stimulant drugs is increasing in Australia and globally. Ecstasy can cause death within hours of ingestion but this occurs only in a small number of users. In contrast, there is recent compelling evidence that a large proportion of users of this drug develop significant and irreversible brain damage due to its use. This latter toxicity is insidious in that it may not become evident to users as impaired brain function until years after their drug use. As a result of ....The use of ecstasy and similar stimulant drugs is increasing in Australia and globally. Ecstasy can cause death within hours of ingestion but this occurs only in a small number of users. In contrast, there is recent compelling evidence that a large proportion of users of this drug develop significant and irreversible brain damage due to its use. This latter toxicity is insidious in that it may not become evident to users as impaired brain function until years after their drug use. As a result of the emerging scientific evidence, The National Institute of Drug Abuse in the USA has recognised the major adverse health impact of these drugs in a recent inititative. The brain has a blood brain barrier to stop toxic substances entering, but we postulate that this is damaged by the immediate effects of ecstasy. This allows acces of toxic breakdown products from the drug to enter the brain and cause the long term damage. If we understand the biological mechanisms which link the immediate and long term effects of ecstasy, we should be in a position to design strategies or therapies which limit its harmful effects. The purpose of this project is to 1. establish if the blood brain barrier is damaged by ecstasy 2. identify environmental factors which contribute to the severity of the toxic effects. We believe that an understanding of these events and the development of evidence based rational treatments for these toxicities is essential: 1 in the short term, to prevent injury and death from these drugs,and 2 in the long term, to prevent a potential major public health problem from neurodegenerative deficits that may be magnified as users age. We believe that our group has the ideal mix of expertise and state of the art methods to make a significant advance in the understanding these problems.Read moreRead less
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
A Trial Of Therapeutic Drug Monitoring In Methadone Maintenance Treatment
Funder
National Health and Medical Research Council
Funding Amount
$542,025.00
Summary
Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to ....Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to switch to alternative therapies. This provides an objective method of planning treatment that focuses on suppressing heroin use. The potential subjects of the study are the 50% of patients who continue to use heroin regularly during treatment. All will undergo assessment involving measurement of blood levels of methadone, testing of effects and side-effects of methadone, and monitoring of safety. Half will be randomly allocated to usual care, and half to therapeutic drug monitoring, with dose adjustments according to the results of testing. At 3 and 6 months all subjects will undergo repeat test sessions. It is hypothesized that those in the experimental group will be using less heroin (confirmed by hair testing). It is expected that the study will also identify a small group of subjects with genetically different opioid receptors, who will require very high doses of methadone to be stabilized. The study will allow a detailed analysis of how best to monitor dose adequacy; the relationship between withdrawal symptoms, methadone blood levels, and heroin use, and will provide the first clear investigation of the relationship between changes in methadone blood concentration and certain potentially dangerous changes in the electrical activity of the heart. The intended outcome of this research project is a model for a higher standard methadone program that is more effective in reducing the problems of heroin use in our community.Read moreRead less
Neuropathways And Synaptic Adaptations Underlying Drug Addiction In Central Dopamine Systems
Funder
National Health and Medical Research Council
Funding Amount
$184,812.00
Summary
There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells undergo long-term depression (LTD) and potentiation (LTP) of ....There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells undergo long-term depression (LTD) and potentiation (LTP) of synaptic strength when excitatory inputs to DA cells are stimulated. These findings are important to drug addiction as amphetamine has been shown to block LTD and enhance LTP in brain slices of DA cells. Thus, changes in LTD and LTP by illicit drugs may underlie the conditions necessary for expression of drug-induced behavioural sensitisation, the best-accepted model of drug-craving in human addiction. To date, these studies have all been conducted in brain slices. Therefore, the functional importance of this synaptic plasticity in midbrain DA cells has yet to be shown in terms of changes in DA release in forebrain terminals in the living animal. For the first time we will address this issue by recording DA cell firing activity together with DA release using a newly developed technique that permits DA release to be monitored in the living brain in 'real-time' (100,000 samples-sec). This will allow us to identify the origin (cortical excitatory inputs) and receptor mechanisms that mediate LTP and LTD in DA cells and their effects on DA release. Recording DA cell activity with real-time measurement of DA release will promote a new cutting-edge technology to the Australian Neurosciences. These data will provide 'first of its kind' evidence of the functional anatomy and receptor mechanisms underlying synaptic plasticity in DA neurons associated with repeated drug use and ultimately enhance our basic understanding of the neural mechanisms of human drug addiction.Read moreRead less
Cortictropin Releasing Factor As A Therapeutic Target For Alcohol And Drug Abuse
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
A key problem with alcoholism, as with addiction generally, is the chronically relapsing nature of the disorder. This can be modelled in rodents and there is good general correspondence between animal studies of reinstatement and human experience of relapse. We have identified brain chemicals involved in this process. Consequently, by better understanding the biological mechanisms related to addiction and relapse, we will be in a position to counter this devastating condition.