Striatal D2 receptor availability will be ascertained in 30 recent abstinent cocaine addicts by [123I]IBZM SPECT. In addition, we will measure drug craving and impulsivity with questionnaires, fMRI/EEG using cue-reactivity and impulsivity paradigms…
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Brief title
Condition
- Other condition
Synonym
Health condition
verslaving
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Research assesing the availability of striatal D2 receptors.
Craving and impulsivity.
Research assesing the respons towards cocaine-associated "cues".
Rimonabant may induce an increased availability of striatal D2 receptors. This
could subsequently reduce craving to cocaine and/or impulsivity in human
cocaine users.
Secondary outcome
not applicable
Background summary
Cocaine addiction creates clear medical and social problems worldwide. Until
now, there is no proven effective medication for the treatment of cocaine
dependence. Treatment of cocaine addiction is hampered by high rates of relapse
even after prolonged periods of drug abstinence. Disruptions in the
dopaminergic system are implicated in the etiology of drug addiction, including
drug craving and impulsivity, and this may contribute to relapse in cocaine
addicts. For example, striatal dopamine D2 receptor availability in chronic
cocaine users has been shown to be less than in controls, and low D2 receptor
availability promotes cocaine self-administration in non-human primates and
rats. The concentration of striatal D2 receptors may be negatively correlated
to craving, which contributes to relapse. If striatal D2 receptor availability
were increased, then perhaps relapse by cocaine addicts may be prevented.
Rimonabant (SR141716A) is a selective cannabinoid receptor 1 (CB1) receptor
antagonist that may increase the availability of D2 receptors, and could
attenuate relapse induced by re-exposure to cocaine or cocaine-associated cues
in rats. Rimonabant is therefore a promising new pharmacological agent to
decrease the risk of relapse in cocaine addicts. The effects of rimonabant on
the neurobiology of cocaine addiction, drug craving, impulsivity and relapse
may be elucidated by comparing striatal D2 receptor availability, drug craving
and impulsivity in abstinent cocaine addicts maintained on rimonabant to those
taking a placebo.
Study objective
Striatal D2 receptor availability will be ascertained in 30 recent abstinent
cocaine addicts by [123I]IBZM SPECT. In addition, we will measure drug craving
and impulsivity with questionnaires, fMRI/EEG using cue-reactivity and
impulsivity paradigms. Relapse will be assessed by checking urine samples every
week.
Study design
Participants will be divided into two groups: one group will receive rimonabant
(n=15; 20 mg/day) and the other will receive placebo (n=15) for 2 months
(double-blind, randomized study design). Drug craving and impulsivity will be
assessed three times: at the beginning of the trial, after intake of the first
tablet (to assess acute effects) and at the end of the trial (after 2 months).
D2 receptor availability will be assessed twice: at the beginning of the trial
and at the end. In addition, each participant will receive cognitive-behavioral
therapy in 45-minute weekly sessions for the duration of the trial.
Study burden and risks
The burden for each participant consists of exposures to each of the
following:2 IBZM SPECT scans, 3 fMRI/EEG scans, and questionnaires and
neuropsychological testing. In addition, one venous blood sample (to assess the
concentration of rimonabant) and weekly urine specimens (for benzoylecgonine
tests) will be obtained. Participants will also ingest either rimonabant or
placebo daily for 2 months.
The risks for the participants are: radiation burden (within the WHO criteria
for research in human) and possible side effects of the rimonabant (this is a
registered drug with a mild profile for side-effects) or placebo.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Male, aged 18-60 years;
2) Current DSM-IV diagnosis of cocaine dependence, but recently detoxified and abstinent.
3) Able to provide written informed consent and to comply with all study procedures.
Exclusion criteria
Exclusion Criteria:
1) Currently dependent on any substance other than cocaine or nicotine;
2) Severe neurological or psychiatric disorders (e.g., depression, psychosis, bipolar illness, dementia, or any diseases that require psychotropic medications);
3) Serious medical illnesses
4) Known hypersensitivity or allergy to rimonabant, or receiving chronic therapy with medication that could interact adversely with one of the medications under study, within 30 days prior to randomization;
5) Drugs known to influence binding to DA2 receptors, including neuroleptics, and methylphenidate
6) Received a drug with known potential for toxicity to a major organ system within the month prior to entering treatment
7) Clinically significant abnormal laboratory values;
8) Any disease of the gastrointestinal system, liver, or kidneys which could result in altered metabolism or excretion of the study medication
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005456-17-NL |
| CCMO | NL19664.018.07 |