Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)
Status:
Not yet recruiting
Trial end date:
2026-12-31
Target enrollment:
Participant gender:
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.