Brain Imaging for Opioid Use Disorder

Overseen By Sarah Yip, PhD, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Methadone

Disqualifiers: Psychosis, Mania, Severe substance-use, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 12 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand how the brain changes during different stages of medication treatment for opioid use disorder. Researchers use fMRI (Functional Magnetic Resonance Imaging) scans to observe how the brains of individuals on methadone adapt over time. The goal is to identify opportunities for additional treatments based on brain activity. This trial suits those in the first six months of stable methadone treatment who are eligible for MRI scans and can commit to regular study visits. As an unphased trial, participants can contribute to groundbreaking research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be on a stable dose of methadone for opioid use disorder. It seems you can continue your methadone treatment while participating.

What prior data suggests that this neuroimaging technique is safe for individuals with opioid use disorder?

Research has shown that functional magnetic resonance imaging (fMRI) is generally safe for people. As a type of brain scan that doesn't use radiation, fMRI is non-invasive. Most people tolerate it well, and no major side effects have been reported.

In studies on opioid use disorder, researchers have used fMRI to study brain function without causing harm. These studies have found no significant risks from fMRI. Participants might experience some discomfort from lying still in the scanner or hearing loud noises during the scan, but these effects are temporary.

Overall, using fMRI in clinical settings is considered safe, and it has been widely used in research for various conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for opioid use disorder, which often involve medications like methadone, buprenorphine, or naltrexone, the use of fMRI in this trial is all about understanding the brain's inner workings. Researchers are excited about this approach because fMRI can provide detailed images of brain activity, helping to identify unique neural patterns, or "fingerprints," associated with the disorder. This could lead to more personalized treatment strategies, targeting specific brain areas to improve outcomes for individuals struggling with opioid use disorder.

What evidence suggests that fMRI is effective for studying opioid use disorder?

Research shows that using fMRI, a type of brain scan, to study opioid use disorder (OUD) provides important insights into how the brain changes during treatment. In this trial, participants will undergo fMRI scans to explore these changes. Studies have found that resting-state fMRI identifies brain networks affected in people with OUD. This scan reveals how opioid medications and withdrawal influence brain activity, which might help improve treatments. Although fMRI is not a treatment itself, it aids in understanding the brain's role in addiction and recovery, potentially leading to better therapies. Early findings suggest that observing these brain changes can pinpoint key times for intervention and support recovery efforts. ^{1 6 7 8 9}

Who Is on the Research Team?

Sarah Yip, PhD, MSc

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals who are undergoing treatment for opioid use disorder. The study focuses on the different phases of medication-based treatment, including starting medication, stabilizing, continuing treatment, and stopping medication. Specific eligibility criteria were not provided.

Inclusion Criteria

Willing to commit to longitudinal study visits

I've been on a stable methadone dose for OUD for up to 6 months.

Eligibility for MRI scanning

Exclusion Criteria

I have had a head injury with unconsciousness for over 30 minutes.

Current intoxication or acute withdrawal at time of study visit sufficient to prevent participation based on: behavioral observation, breathalyzer, and SOWS assessment (these individuals will be allowed to enroll at a later date once stable)

Past or present history of intellectual disability or developmental disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 hours

1 visit (in-person)

Treatment

Participants undergo fMRI scans and computational assessments during early methadone treatment

12 weeks

6 visits (in-person for fMRI), 12 visits (virtual for computational assessment)

Follow-up

Participants are monitored monthly for additional insights post-treatment

3 months

3 visits (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• fMRI

Trial Overview

The trial is using functional Magnetic Resonance Imaging (fMRI) to track changes in brain activity over time during the various stages of Medication for Opioid Use Disorder (MOUD). It aims to understand how recovery works on a neurological level and identify key moments when additional treatments could be most effective.

How Is the Trial Designed?

Group I: neural fingerprinting of MOUD Experimental Treatment 1 Intervention

Study participants will have one in-person screening (2 hours), 6 in-person visits for fMRI scans conducted biweekly (4 hours), and will be computationally assessed 12 times, once per week for 12 weeks. After participation in the main study, participants will be asked to complete a 15-minute follow up every month for an additional three months

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study involving 37 male heroin addicts, those in short-term abstinence showed heightened brain activity in response to heroin-related cues, indicating stronger cravings and withdrawal symptoms compared to those in long-term abstinence.

Long-term abstinence was associated with reduced neural responses to heroin cues and less severe withdrawal symptoms, suggesting that prolonged abstinence may help diminish the impact of drug-related triggers and lower the risk of relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cue-elicited craving in heroin addicts at different abstinent time: an fMRI pilot study. Lou, M., Wang, E., Shen, Y., et al.[2022]

Individuals with opioid-use disorder (OUD) show increased brain activation in response to heroin cues, which is influenced by medication-assisted treatments and can predict treatment outcomes.

Despite these insights, there is a lack of research on the neural mechanisms of OUD and its treatments, highlighting the need for more studies, especially focusing on prescription opioid users and sex differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can neuroimaging help combat the opioid epidemic? A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research. Moningka, H., Lichenstein, S., Worhunsky, PD., et al.[2023]

Chronic pain patients using prescription opioids showed weaker frontostriatal resting-state functional connectivity and reduced gray matter volume in key brain areas compared to healthy controls, indicating structural and functional brain changes associated with opioid use.

These brain abnormalities were linked to higher levels of negative affect and severity of opioid misuse, suggesting that the changes in frontostriatal circuitry may contribute to ongoing opioid dependence and highlight the need for targeted interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired frontostriatal functional connectivity among chronic opioid using pain patients is associated with dysregulated affect. McConnell, PA., Garland, EL., Zubieta, JK., et al.[2021]

Functional magnetic resonance imaging (fMRI) has identified quantitative biomarkers related to brain activity in individuals with drug addictions, which could be useful for various stages of addiction treatment, from screening to post-treatment follow-up.

Despite the potential of fMRI in addiction medicine, there is a significant gap between group-based research findings and their application in personalized treatment, highlighting the need for large-scale clinical trials to better integrate these insights into everyday practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional neuroimaging for addiction medicine: From mechanisms to practical considerations. Ekhtiari, H., Faghiri, A., Oghabian, MA., et al.[2017]

A preliminary study involving 26 individuals with prescription opioid use disorder (POUD) and 21 healthy controls found that structural MRI (sMRI) revealed reduced integrity in brain regions associated with addiction, indicating potential neural changes due to long-term opioid use.

Multivariate machine learning approaches combining sMRI and resting-state functional connectivity (restFC) features achieved a classification accuracy of 66.7%, suggesting that these neuroimaging methods can effectively distinguish between POUD and healthy individuals, paving the way for future predictive models in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural MRI and functional connectivity features predict current clinical status and persistence behavior in prescription opioid users. Mill, RD., Winfield, EC., Cole, MW., et al.[2021]

This study is the first to use fMRI to observe the immediate effects of heroin on brain function, involving four opiate addicts who were scanned before and after receiving a 30 mg dose.

Results indicated that heroin administration led to a decrease in brain activation during a visual task, suggesting that heroin may impair brain function in response to stimuli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance imaging of the acute effect of intravenous heroin administration on visual activation in long-term heroin addicts: results from a feasibility study. Sell, LA., Simmons, A., Lemmens, GM., et al.[2019]

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This mini-review examines functional connectivity in resting-state functional magnetic resonance imaging (rs-fMRI) among opioid users.

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a longitudinal structural magnetic resonance imaging study

Our study suggests XR-NTX-induced cortical thickness reduction in the mPFC/aCC regions in OUD patients.

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The purpose of Project 2 is to execute phase I functional magnetic resonance imaging (fMRI) studies to assess the effects of lorcaserin on brain target ...

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Brain Volume Changes Seen in Opioid Users

The data included structural MRI and functional MRI (fMRI) exams performed between February 2021 and May 2023. Researchers analyzed CLOUDS ...