BED IN 43: Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)
Study Details
Study Description
Brief Summary
The overarching hypotheses of this protocol are that (1) persistent brain glutamate changes induced by chronic opioid use will exacerbate use of cocaine during opioid physical dependence and withdrawal and (2) n-acetylcysteine (NAC) will ameliorate glutamatergic dysregulation, and thus will reduce both opioid and cocaine demand. These hypotheses will be tested with two specific aims.
Specific Aim 1. Determine the reinforcing effects of cocaine in individuals with comorbid opioid and cocaine use disorder with physiological dependence on opioids during NAC maintenance. All subjects will be maintained on oral hydromorphone. They will also be randomly assigned to receive placebo or oral NAC (2.4 g/day), stratified by sex. After dose stabilization, experimental sessions will be conducted in which subjects complete hypothetical cocaine purchase tasks during opioid maintenance and opioid withdrawal. The hypotheses are: 1) cocaine purchasing will be greater during opioid withdrawal and 2) NAC maintenance will attenuate cocaine purchasing across opioid maintenance and withdrawal periods.
Specific Aim 2. Evaluate glutamate functionality during periods of opioid maintenance and withdrawal in individuals with comorbid opioid and cocaine use disorder and physiological dependence on opioids during NAC maintenance. Subjects will undergo magnetic resonance spectroscopy to evaluate brain glutamate changes as a function of opioid maintenance/withdrawal state and NAC maintenance. The hypotheses are: 1) glutamate levels will be elevated during opioid withdrawal and 2) NAC maintenance will ameliorate elevated glutamate levels.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: n-Acetylcysteine Subjects will receive 0.6 g oral n-acetylcysteine 4 times per day. |
Drug: n-acetylcysteine
Subjects will be randomized to receive 2.4 oral n-acetylcysteine daily.
Drug: Hydromorphone
Subjects will receive up to 90 mg oral hydromorphone daily.
Drug: Placebo hydromorphone
Prior to some experimental sessions, subjects will receive placebo hydromorphone
|
| Placebo Comparator: Placebo Subjects will receive oral placebo 4 times per day. |
Drug: Hydromorphone
Subjects will receive up to 90 mg oral hydromorphone daily.
Drug: Placebo n-acetylcystine
Subjects will be randomized to receive placebo n-acetylcysteine daily.
Drug: Placebo hydromorphone
Prior to some experimental sessions, subjects will receive placebo hydromorphone
|
Outcome Measures
Primary Outcome Measures
- Hypothetical opioid purchasing [After at least seven days of maintenance on n-acetylcysteine or placebo]
Amount of opioids purchased on a hypothetical purchase task
- Hypothetical cocaine purchasing [After at least seven days of maintenance on n-acetylcysteine or placebo]
Amount of cocaine purchased on a hypothetical purchase task
- Glutamate function [After at least seven days of maintenance on n-acetylcysteine or placebo]
Magnetic resonance spectroscopy of brain glutamate levels
- Gamma Aminobutyric Acid (GABA) function [After at least seven days of maintenance on n-acetylcysteine or placebo]
Magnetic resonance spectroscopy of brain GABA levels
Secondary Outcome Measures
- Craving [After at least seven days of maintenance on n-acetylcysteine or placebo]
Scores on a locally developed craving scale from 1-10, with higher scores indicating more craving
- Subjective opioid withdrawal [After at least seven days of maintenance on n-acetylcysteine or placebo]
Self-reported scores on the Subjective Opioid Withdrawal Scale with scores from 0-64, with higher scores indicating more withdrawal
- Clinical opioid withdrawal [After at least seven days of maintenance on n-acetylcysteine or placebo]
Self-reported scores on the Clinical Opioid Withdrawal Scale with scores from 0-48, with higher scores indicating more withdrawal
Other Outcome Measures
- Side effects [Daily during approximately 10 day inpatient admission]
Scores on the Udvalg Fur Kliniske Undersolgelser (UKU) side effects scale with scores from 0-3, with higher scores indicating greater side effects
- Pupil diameter [Daily during approximately 10 day inpatient admission]
Measurement of pupil diameter using an automated scanner
- Heart rate [Daily during approximately 10 day inpatient admission]
Measurement of heart rate using an automated monitor
- Respiration rate [Daily during approximately 10 day inpatient admission]
Measurement of respiration rate using an automated monitor
- Oxygen saturation [Daily during approximately 10 day inpatient admission]
Measurement of oxygen saturation using an automated monitor
- Diastolic blood pressure [Daily during approximately 10 day inpatient admission]
Measurement of diastolic blood pressure using an automated monitor
- Systolic blood pressure [Daily during approximately 10 day inpatient admission]
Measurement of systolic blood pressure using an automated monitor
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Between the ages of 18 and 55 years,
-
Report recent use of opioids and cocaine and must not be seeking treatment for their drug use,
-
Be physically dependent on short-acting opioids,
-
Meet Diagnostic and Statistical Manual (DSM)-5 diagnostic criteria for current opioid use disorder (OUD) and current or past cocaine use disorder (CUD) and have either a urine sample positive for recent opioid use during each visit or if opioid negative, displaying frank withdrawal during screening
-
Other than the diagnosis for opioid and cocaine use disorder at the time of the screening, subjects must be healthy,
-
Laboratory chemistries (e.g., blood chemistry screen, complete blood count, urinalysis) and electrocardiogram (ECG) results must be normal or within normal range and any abnormal results must be considered as not clinically significant by the study physicians,
-
No contraindications to magnetic resonance imagining (MRI; e.g., metallic objects in their body, BMI > or = 40, claustrophobia) will be considered ineligible,
-
Female subjects must be using an effective form of birth control (e.g., birth control pills, surgical sterilization, intrauterine device, barrier method, condoms with spermicide, cervical cap with a spermicide or abstinence) to participate and must not be pregnant,
-
All study subjects will be judged by the medical staff to be psychiatrically and physically healthy.
Exclusion Criteria:
-
Any potential subject with a history of serious physical disease, current physical disease (e.g., impaired cardiovascular functioning, histories of seizure, head trauma, diabetes, asthma, or central nervous system [CNS] tumors) or current or past histories of serious psychiatric disorder (e.g., schizophrenia) that would limit compliance in the study, other than substance use disorder, will be excluded from research participation,
-
Potential subjects that meet diagnostic criteria for moderate - severe substance use disorder for substances other than opioids, stimulants, cannabis, or nicotine at the time of the interview will not be eligible for study participation,
-
Subjects who report a positive first-degree family history of schizophrenia, serious cardiovascular disease, or seizure disorders will also be excluded from research participation.
-
Subjects with contraindications to hydromorphone or n-acetylcysteine will not be eligible.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Kentucky Laboratory of Human Behavioral Pharmacology | Lexington | Kentucky | United States | 40507 |
| 2 | University of Kentucky Department of Behavioral Science | Lexington | Kentucky | United States | 40536-0086 |
Sponsors and Collaborators
- William Stoops
- National Institute on Drug Abuse (NIDA)
Investigators
- Principal Investigator: William W Stoops, University of Kentucky
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 80485
- R33DA049130