It is expected that the cocaine and alcohol dependent subjects will display higher impulsivity on impulsivity-related tasks in the current study compared to healthy control subjects and show altered frontostriatal activity associated with…
ID
Bron
Verkorte titel
Aandoening
cocaine dependence, alcohol dependence
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
The main outcome measures are craving ratings, self-report impulsivity, neuropsychological performance (mean reaction time and accuracy) and the fMRI blood oxygen level dependent (BOLD) response. These measures will be evaluated between groups (cocaine/alcohol/control) and within groups (placebo versus medication).
Achtergrond van het onderzoek
During the development of substance dependence, drug-associated stimuli become increasingly relevant to the substance user. In addition to the role of motivational cues, deficits in cognitive functioning play a key role in addiction. In particular, cognitive functions that involve behavioural control, and also control over behaviour when confronted with motivationally relevant drug cues, appear to be crucial for the development and course of addictive disorders. We will study the neural substrates of these two processes and their interaction. The interrelation between poor impulse control, motivational relevance of drug cues, and vulnerability to relapse predicts that improving cognitive performance may represent a promising new approach in the treatment of addiction. We therefore present a pharmacological challenge study with (1) a cognitive enhancer (studied in humans with cocaine dependence: modafinil), and (2) an agent influencing the motivational relevance of drug cues in animals (N-acetylcysteine). Thirty alcohol dependent patients, thirty cocaine dependent patients and thirty healthy controls will be tested using neurocognitive tasks on impulsivity and motivational drug cues in an fMRI study both before and after acute administration with N-acetylcysteine, modafinil, or placebo.
Doel van het onderzoek
It is expected that the cocaine and alcohol dependent subjects will display higher impulsivity on impulsivity-related tasks in the current study compared to healthy control subjects and show altered frontostriatal activity associated with impulsivity.
N-acetylcysteine is expected to have its primary effect on motivationally relevant cues (i.e. drug cues, reward cues), and is thus expected to influence mesocorticolimbic and orbitofrontal brain functioning.
Several studies have indicated that modafinil strongly reduces impulsive behaviour. Therefore, it is expected that the inclusion of modafinil will primarily exert its effect on brain areas related to cognitive control, such as the dorsolateral prefrontal cortex and the anterior cingulate cortex.
Onderzoeksopzet
1. First fMRI session with placebo or medication;
2. Second fMRI session with placebo or medication (cross-over design) within two weeks after first session;
3. Follow-up after 3 and 6 months to investigate relapse rate.
Onderzoeksproduct en/of interventie
Cocaine dependent, alcohol dependent patients and healthy controls will receive an acute administration with both NAC/modafinil and a placebo during two fMRI sessions in a double-blind cross-over design. Subjects will be randomly allocated to receive placebo or medication during the first session. During the two sessions, subjects will perform cognitive tasks inside and outside a MRI scanner. Functional and structural MRI images will be obtained. Subjects will also fill out questionnaires and a diagnostic interview will be administered. In addition, urine and DNA samples will be obtained.
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Male, age 18-60 years;
2 For the alcohol dependent group: current DSM-IV diagnosis of alcohol dependence, but recently detoxified and abstinent and not using benzodiazepines for at least one week;
3. For the cocaine dependent group: current DSM-IV diagnosis of cocaine dependence, but recently detoxified and abstinent and not using benzodiazepines for at least one week;
4. For the healthy control group: matched on gender, ethnicity, age and education to the alcohol and cocaine dependent groups.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Current use of prescription or illicit psychoactive drugs;
2. Lifetime history of head injury with loss of consciousness for more than 5 minutes;
3. Serious neurological or psychiatric disorders (e.g. psychosis, dementia, bipolar disorder, major depressive disorder);
4. More than 100 lifetime uses of any class of drug of abuse other than alcohol (alcohol group) or cocaine (cocaine group);
5. Being on an active low-calorie (<1000 calories/day) diet;
6. Unstable medical illness (e.g. hypertension, diabetes, myocardial infarct);
7. Colour blindness;
8. Currently dependent on cocaine for the alcohol dependent group and currently dependent on alcohol for the cocaine dependent group;
9. Less than a lower level education until age 16;
10. With respect to MRI imaging: claustrophobia; presence of non-removable metal objects, use of psychotropic medication;
11. With respect to the medications: use of medication affecting the central nerve system (such as anti-depressants); use of antibiotics, hypersensitivity for modafinil or N-acetylcysteine; history of peptic ulceration, asthma.
Opzet
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In overige registers
Register | ID |
---|---|
NTR-new | NL2005 |
NTR-old | NTR2122 |
CCMO | NL24576.018.08 |
ISRCTN | ISRCTN wordt niet meer aangevraagd. |
OMON | NL-OMON33825 |