Glutamatergic Modulation of Cocaine-related Deficits
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric, Pulmonary |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 21 - 52 |
| Updated: | 9/20/2018 |
| Start Date: | February 2011 |
| End Date: | March 2012 |
The Effect of Ketamine on Reducing Cue Reactivity in Cocaine Users
Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to
cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits.
Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators,
studies with human subjects have been unsuccessful to date. The purpose of this investigation
is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent
therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting
cocaine in cocaine dependent participants, 24-hours post-infusion.
cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits.
Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators,
studies with human subjects have been unsuccessful to date. The purpose of this investigation
is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent
therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting
cocaine in cocaine dependent participants, 24-hours post-infusion.
In this study, volunteers will undergo a 9 day inpatient trial during which they will receive
three counter-balanced infusions (two doses of ketamine and a dose of lorazepam) on three
separate days in a within-subject, double-blind, controlled design. Of the various glutamate
antagonists available for human use, ketamine will be utilized because its safety profile,
pharmacokinetics, and range of tolerable sub-anesthetic dosings have been very well studied.
Also, ketamine has shown promise in managing opiate and alcohol use disorders in certain
studies, and may therefore be the most likely glutamate antagonist to dampen cue reactivity
and increase motivation in cocaine users. If ketamine significantly improves these deficits,
this would suggest that the drug should be investigated further for potential utility as a
treatment for cocaine dependence.
three counter-balanced infusions (two doses of ketamine and a dose of lorazepam) on three
separate days in a within-subject, double-blind, controlled design. Of the various glutamate
antagonists available for human use, ketamine will be utilized because its safety profile,
pharmacokinetics, and range of tolerable sub-anesthetic dosings have been very well studied.
Also, ketamine has shown promise in managing opiate and alcohol use disorders in certain
studies, and may therefore be the most likely glutamate antagonist to dampen cue reactivity
and increase motivation in cocaine users. If ketamine significantly improves these deficits,
this would suggest that the drug should be investigated further for potential utility as a
treatment for cocaine dependence.
Inclusion Criteria
1. Active free-base cocaine dependence (at least 4 days of use over the past month, with
at least 1 use per week); if the participant uses through another route (IN, IV), then
the FB route is dominant (> 80% of occasions).
2. Physically healthy
3. No adverse reactions to study medications
4. 21-52 years of age
5. Normal body weight
6. Responsive to drug cues
7. Capacity to consent
Exclusion Criteria:
1. Seeking treatment or abstinence
2. DSM IV criteria for substance dependence (other than methamphetamine, cocaine,
cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam
3. DSM-IV criteria for other Axis I psychiatric illness that may make participation
hazardous such as schizophrenia, schizoaffective disorder, psychosis NOS, MDD,
psychosis secondary to substances, or bipolar disorder
4. Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
5. Current suicide risk or a history of suicide attempt within the past 2 years
6. Current use of prescribed psychotropic medication
7. Pregnancy, nursing, or had a baby within the past 6 mo.
8. Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
9. Unstable physical disorders which might make participation hazardous such as end-stage
AIDS, hypertension (>140/90), anemia, active hepatitis or other liver disease, or
diabetes
10. "Bad" reaction/experience with prior exposure to ketamine or lorazepam
11. History of significant violence
12. First degree relative with a psychotic disorder
We found this trial at
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