Cocaine Use DisorderEarly Phase 1BED IN 43NCT05610072
Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)
A Early Phase 1 study testing n-acetylcysteine and Hydromorphone in people with Cocaine Use Disorder and Opioid Use Disorder, run by William Stoops at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cocaine Use Disorder, Opioid Use Disorder, Stimulant Use Disorder
- What is being tested?
- n-acetylcysteine and Hydromorphone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Dec 2022to 27 Mar 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Kentucky Laboratory of Human Behavioral Pharmacology
Lexington, Kentucky, 40507
University of Kentucky Department of Behavioral Science
Lexington, Kentucky, 40536-0086
About this study
Official title: Glutamatergic Mechanisms in Opioid and Cocaine Co-Use
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.
- Being tested
- n-acetylcysteine, Hydromorphone, Placebo n-acetylcystine, Placebo hydromorphone
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
n-acetylcysteineDrug
Subjects will be randomized to receive 2.4 oral n-acetylcysteine daily.
HydromorphoneDrug
Subjects will receive up to 192 mg oral hydromorphone daily.
Placebo n-acetylcystineDrug
Subjects will be randomized to receive placebo n-acetylcysteine daily.
Placebo hydromorphoneDrug
Prior to some experimental sessions, subjects will receive placebo hydromorphone
| Study group | Role | What they receive |
|---|---|---|
| n-Acetylcysteine | Experimental | Subjects will receive 0.6 g oral n-acetylcysteine 4 times per day. Receives: Drug: n-acetylcysteine; Drug: Hydromorphone; Drug: Placebo hydromorphone |
| Placebo | Placebo comparator | Subjects will receive oral placebo 4 times per day. Receives: Drug: Hydromorphone; Drug: Placebo n-acetylcystine; Drug: Placebo hydromorphone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypothetical opioid purchasing
Amount of opioids purchased on a hypothetical purchase task
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Hypothetical cocaine purchasing
Amount of cocaine purchased on a hypothetical purchase task
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Glutamate function
Magnetic resonance spectroscopy of brain glutamate levels
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Gamma Aminobutyric Acid (GABA) function
Magnetic resonance spectroscopy of brain GABA levels
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Secondary outcomes (3)
Craving
Scores on a locally developed craving scale from 1-10, with higher scores indicating more craving
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Subjective opioid withdrawal
Self-reported scores on the Subjective Opioid Withdrawal Scale with scores from 0-64, with higher scores indicating more withdrawal
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Clinical opioid withdrawal
Self-reported scores on the Clinical Opioid Withdrawal Scale with scores from 0-48, with higher scores indicating more withdrawal
Measured: After at least seven days of maintenance on n-acetylcysteine or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2022
- Study start15 Dec 2022
- Primary completion27 Mar 2026
- Study completion27 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cocaine Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- William Stoops
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor-investigator, William Stoops, University of Kentucky
- Investigators
- William W Stoops, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05610072
- Sponsor's protocol ID
- 80485
- Other IDs
- R33DA049130
- Acronym
- BED IN 43
- Status last verified
- Apr 2026
- First submitted
- 31 Oct 2022
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamatergic Mechanisms in Opioid and Cocaine Co-Use
- ClinicalTrials.gov ID
- NCT05610072
- Acronym / sponsor ID
- BED IN 43 / 80485
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- William StoopsUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 15 Dec 2022 (actual)
- Primary completion
- 27 Mar 2026 (actual)
- Study completion
- 27 Mar 2026 (actual)
- First posted
- 9 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| n-Acetylcysteine | Experimental | Drug: n-acetylcysteine, Drug: Hydromorphone, Drug: Placebo hydromorphoneSubjects will receive 0.6 g oral n-acetylcysteine 4 times per day. |
| Placebo | Placebo comparator | Drug: Hydromorphone, Drug: Placebo n-acetylcystine, Drug: Placebo hydromorphoneSubjects will receive oral placebo 4 times per day. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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,
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| n-acetylcysteineSubjects will be randomized to receive 2.4 oral n-acetylcysteine daily. | Drug | n-Acetylcysteine |
| HydromorphoneSubjects will receive up to 192 mg oral hydromorphone daily. | Drug | Placebo, n-Acetylcysteine |
| Placebo n-acetylcystineSubjects will be randomized to receive placebo n-acetylcysteine daily. | Drug | Placebo |
| Placebo hydromorphonePrior to some experimental sessions, subjects will receive placebo hydromorphone | Drug | Placebo, n-Acetylcysteine |
Primary outcome
Hypothetical opioid purchasing
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Amount of opioids purchased on a hypothetical purchase task
Hypothetical cocaine purchasing
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Amount of cocaine purchased on a hypothetical purchase task
Glutamate function
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Magnetic resonance spectroscopy of brain glutamate levels
Gamma Aminobutyric Acid (GABA) function
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Magnetic resonance spectroscopy of brain GABA levels
3 secondary outcomes
Craving
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Subjective opioid withdrawal
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Clinical opioid withdrawal
Time frame: After at least seven days of maintenance on n-acetylcysteine or placebo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William W Stoops principal investigator
University of Kentucky
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing n-acetylcysteine and Hydromorphone in people with Cocaine Use Disorder and Opioid Use Disorder, run by William Stoops at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hypothetical opioid purchasing (time frame: After at least seven days of maintenance on n-acetylcysteine or placebo). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.