NCT05610072

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

Glutamatergic Mechanisms in Opioid and Cocaine Co-Use

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: William Stoops · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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

Type	Name	Description
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 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

Timeline

• Start date: 2022-12-15
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2022-11-09
• Last updated: 2025-12-11

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study