Clinical Outcome Assessment Development for Opioid Use Disorder

Overseen By Cecilia L Bergeria, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Must not be taking: Naltrexone

Disqualifiers: Pregnancy, Psychosis, Suicidal behavior, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to develop a better assessment tool for understanding opioid cravings to improve treatments for opioid use disorder. Participants will interact with various objects, some neutral and some related to opioids, and then share their thoughts and feelings about the experience. This process includes evaluating their responses to different cues, which may induce cravings. Participants will also provide feedback on existing craving assessments. Individuals currently receiving treatment for opioid use disorder and who test positive for opioids at their initial visit might be suitable for this trial. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future treatment strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does exclude individuals receiving Naltrexone, so you may need to discuss your current medications with the trial team.

What prior data suggests that these cue-induced craving tasks are safe for participants?

Research has shown that tasks designed to trigger cravings are generally safe for participants. In studies on opioid use disorder, researchers present drug-related cues, such as pictures or objects associated with opioids, to observe changes in cravings. These studies usually find that while these cues can increase cravings, they do not cause harmful side effects. Participants look at and sometimes handle objects, which are standard methods in craving studies. No significant reports of negative effects have been directly linked to these activities. The main goal is to better understand cravings, not to introduce new risks. Therefore, participants generally tolerate these activities well, and they are considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for opioid use disorder because they focus on understanding and manipulating craving responses in a unique way. Unlike standard treatments such as methadone, buprenorphine, or naltrexone, which primarily address the biochemical aspects of addiction, these new approaches utilize visual and tactile cues to explore how cravings can be induced or reduced. By targeting the psychological triggers of cravings, this research could lead to innovative therapeutic strategies that complement existing medications, offering a more comprehensive approach to managing addiction.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

Research shows that people with opioid addiction can experience strong cravings when they encounter drug-related cues, such as pictures or objects. Studies have found that these cravings can increase the likelihood of opioid relapse. One study found that the brain reacts to these cues by increasing stress levels, which can intensify cravings. This trial will assess different cue-induced craving tasks, such as visual and tactile opioid cues, to better understand and measure these cravings. These findings suggest that understanding and measuring these cravings could lead to better treatments for opioid addiction. ^{1 2 3 4 6}

Who Is on the Research Team?

Cecilia L Bergeria, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are currently in treatment for opioid use disorder and have tested positive for opioids, excluding those on Naltrexone. It's not open to individuals with other substance disorders (except nicotine), pregnant or breastfeeding women, those at risk of incarceration, intoxicated persons, or people with recent suicidal behavior or serious psychiatric issues.

Inclusion Criteria

Opioid-positive urine sample at admission visit (excluding individuals receiving Naltrexone)

Current opioid use disorder per Diagnostic Statistical Manual (DSM)-5

Currently in treatment for opioid use disorder

Exclusion Criteria

Have circumstances that would interfere with study participation (e.g., impending jail)

Being pregnant or breastfeeding, or may become pregnant during the trial

Positive for illicit substances except opioids and cannabis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cue-Induced Craving Tasks

Participants complete cue-induced opioid craving tasks involving exposure to neutral and opioid-related cues, followed by interviews and questionnaires.

3 sessions (approximately 1 hour each)

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the cue-induced craving tasks

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Neutral Cue-induced Craving
• Visual and Tactile Opioid Cue-induced Craving
• Visual Opioid Cue-induced Craving

Trial Overview The study aims to develop an assessment tool for measuring opioid craving by having participants engage with neutral items and opioid-related images and objects. They will then discuss their experiences in interviews and complete questionnaires about their cravings.

How Is the Trial Designed?

Group I: No Craving Experimental Treatment 3 Interventions

Each participant will attend three sessions where the participant will experience three distinct cue-induced craving tasks in a randomized fashion.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Chronic buprenorphine treatment effectively reduces cocaine intake in rats, but does not affect heroin consumption, indicating a selective efficacy for cocaine addiction.

Buprenorphine treatment enhances dopamine levels in the nucleus accumbens while attenuating the dopamine response to heroin, suggesting it may help reduce the appeal of drug-associated cues and drug-seeking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration. Sorge, RE., Stewart, J.[2018]

In a study of 43 patients with chronic non-cancer pain and opioid use disorder, switching to buprenorphine/naloxone (BuNa) significantly reduced opioid misuse, craving, and psychiatric symptoms such as depression and anxiety over a two-month follow-up.

Patients also reported a decrease in pain levels after the BuNa rotation, suggesting that this treatment could be an effective strategy for managing both pain and opioid dependence, although further research with larger sample sizes is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Opioid Rotation to Buprenorphine/Naloxone on Opioid Misuse, Craving, Mental Health, and Pain Control in Chronic Non-Cancer Pain Patients with Opioid Use Disorder. Schellekens, AFA., Veldman, SE., Suranto, ESD., et al.[2021]

A study involving 53 opioid-dependent patients showed that switching from buprenorphine to buprenorphine/naloxone was well-tolerated, with no significant issues reported during the transition.

Patients expressed a preference for buprenorphine/naloxone over buprenorphine, with 54% favoring the combination formulation due to its taste and ease of use, indicating it may be a more acceptable option for maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. Daulouède, JP., Caer, Y., Galland, P., et al.[2015]

Buprenorphine and buprenorphine/naloxone (BUP/NAL) significantly reduce opioid craving compared to placebo, indicating their efficacy as medications for opioid use disorder (OUD).

However, lower doses of buprenorphine are associated with higher craving levels, and in some studies, buprenorphine was linked to greater craving than methadone and extended-release naltrexone, suggesting that other MOUD may be more effective in managing cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine on opioid craving in comparison to other medications for opioid use disorder: A systematic review of randomized controlled trials. Baxley, C., Borsari, B., Reavis, JV., et al.[2023]

In a study with seven male volunteers, buprenorphine pretreatment significantly reduced the choice of high doses of cocaine while increasing the preference for non-drug alternatives (tokens), suggesting its potential to help reduce cocaine use.

Despite the reduction in cocaine choice, participants still experienced significant intoxication effects from the combination of buprenorphine and cocaine, indicating that while buprenorphine may help curb cocaine use, the overall effects and interactions of these substances are complex and not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine on the self-administration of cocaine by humans. Foltin, RW., Fischman, MW.[2019]

Chronic treatment with buprenorphine (3.0 mg/kg/day) in rats significantly reduced their responses to sucrose-associated cues and decreased reinstatement of sucrose seeking, suggesting its potential to blunt drug-seeking behavior.

While buprenorphine did not significantly affect the dopamine response to sucrose or lab chow, it did increase basal dopamine levels, indicating a complex interaction with the brain's reward system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic buprenorphine reduces the response to sucrose-associated cues in non food-deprived rats. Hood, S., Sorge, RE., Stewart, J.[2014]

Probuphine, an implantable formulation of buprenorphine, was evaluated in 12 heroin-dependent volunteers and showed a continuous and effective delivery of medication over 6 months, maintaining low withdrawal symptoms and cravings.

The study found that 59% of urine tests were opioid-negative during treatment, indicating effective management of opioid dependence, with only mild injection site reactions reported and no serious safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. White, J., Bell, J., Saunders, JB., et al.[2013]

In a study of 43 opioid-dependent patients switched from buprenorphine monotherapy to buprenorphine/naloxone for 24 weeks, the combination therapy effectively controlled cravings and withdrawal symptoms, with 91% of patients rating their management as satisfactory by the end of the study.

The addition of naloxone to buprenorphine significantly reduced the potential for misuse, as only 2% of patients attempted intravenous misuse, and none reported gratifying effects, indicating a safer profile for outpatient treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic switch to buprenorphine/naloxone from buprenorphine alone: clinical experience in an Italian addiction centre. Montesano, F., Zaccone, D., Battaglia, E., et al.[2018]

In a study involving 14 heroin-dependent volunteers maintained on buprenorphine, hydromorphone (HYD) showed minimal reinforcing effects in those who were abstinent from heroin, while non-abstainers experienced significant dose-related increases in HYD's reinforcing value.

The study found that while buprenorphine did not reduce the reinforcing effects of hydromorphone in non-abstainers, it did help reduce heroin craving in a dose-dependent manner, indicating that buprenorphine can effectively manage cravings even in the presence of other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance. Greenwald, MK., Johanson, CE., Schuster, CR.[2019]

Chronic buprenorphine treatment does not affect the locomotor response to heroin but significantly enhances the response to cocaine, indicating a potential risk for increased cocaine use among opioid users on buprenorphine.

Buprenorphine effectively reduces drug-seeking behavior for both heroin and cocaine in rats, suggesting it may help manage cravings in opioid addiction, although it does not prevent stress-induced drug seeking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement. Sorge, RE., Rajabi, H., Stewart, J.[2019]

Buprenorphine, administered in doses ranging from 1.5 to 8.0 mg/day, effectively reduced heroin craving and use in 85 heroin addicts over a maintenance period of 4 to 12 weeks, with 40 participants having no prior treatment.

In a discontinuation trial, those who underwent dose reductions experienced significantly more withdrawal symptoms and cravings compared to those who maintained a stable dose, indicating that careful management of dosage is crucial for successful treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine: an alternative to methadone for heroin dependence treatment. Resnick, RB., Galanter, M., Pycha, C., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4163930/

Cue-Induced Craving in Dependence Upon Prescription ... This study found evidence for cue-induced craving in individuals dependent upon prescription opioids.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05109429

Developing a Clinical Outcome Assessment for Opioid ... The purpose of this study is to collect information about opioid craving so that the investigators can develop an opioid craving assessment to improve ...

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00592/full

Craving in Opioid Use Disorder: From Neurobiology to ... Exposure to drug-related cues mediates the symptoms of craving in OUD (44–49) and may be linked with increased cortisol responses (50), consistent with the ...

4. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06986-y

Exploring the relationship between cue-induced craving and ... The results showed that:1) In the VR cue environment, MUD participants' craving in the drug use scene was significantly higher than in the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8282754/

Laboratory-induced stress and craving predict opioid use ... Findings demonstrate that elevated cue-induced craving, either in the context of a stressor or not, is associated with shortened time to opioid use.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11282646/

Ecological momentary assessment and cue-elicited drug ... A randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.