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Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 55 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  1. Between the ages of 18 and 55 years, 2. Report recent use of opioids and cocaine and must not be seeking treatment for their drug use, 3. Be physically dependent on short-acting opioids, 4. 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 5. Other than the diagnosis for opioid and cocaine use disorder at the time of the screening, subjects must be healthy, 6. 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, 7. No contraindications to magnetic resonance imagining (MRI; e.g., metallic objects in their body, BMI > or = 40, claustrophobia) will be considered ineligible, 8. 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, 9. All study subjects will be judged by the medical staff to be psychiatrically and physically healthy.

Exclusion Criteria

  1. 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, 2. 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, 3. Subjects who report a positive first-degree family history of schizophrenia, serious cardiovascular disease, or seizure disorders will also be excluded from research participation. 4. Subjects with contraindications to hydromorphone or n-acetylcysteine will not be eligible.

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This study will use a double-blind, placebo-controlled design with all subjects receiving all hydromorphone (i.e., hydromorphone dose is a within subject factors). Half of the subjects will receive placebo and half of the subjects will receive 2.4mg/day NAC.
Primary Purpose
Basic Science
Masking
Triple (Participant, Care Provider, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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 192 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 192 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

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky Department of Behavioral Science
Lexington, Kentucky 40536-0086
Contact:
William W Stoops, Ph.D.
859-257-5388
william.stoops@uky.edu

University of Kentucky Laboratory of Human Behavioral Pharmacology
Lexington, Kentucky 40507
Contact:
William W Stoops, Ph.D.
859-257-5388
william.stoops@uky.edu

More Details

NCT ID
NCT05610072
Status
Recruiting
Sponsor
William Stoops

Study Contact

William W Stoops, PhD
8592575388
william.stoops@uky.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.