Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)

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.

Conditions

• Cocaine Use Disorder
• Opioid Use Disorder
• Stimulant Use Disorder

Interventions

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

DRUG

n-acetylcysteine

Subjects will be randomized to receive 2.4 oral n-acetylcysteine daily.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA)

  collaborator NIH

• William Stoops

  lead OTHER

Principal Investigators

• William W Stoops · University of Kentucky

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-12-15

Primary Completion

2026-03-27

Completion

2026-03-27

FDA Drug

Yes

Countries

• United States

Study Locations