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

Trial Summary

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 data supports the effectiveness of brain imaging for opioid use disorder treatment?

Research shows that brain imaging techniques like fMRI can identify changes in brain activity related to opioid use and treatment, which may help in assessing and predicting treatment responses. This suggests that brain imaging could be a useful tool in understanding and managing opioid use disorder. ^{1 2 3 4 5}

Is brain imaging using MRI or fMRI safe for humans?

MRI and fMRI are generally considered safe for humans, as they are non-invasive imaging techniques that do not use radiation. They have been widely used in various studies, including those involving opioid use disorder, without significant safety concerns reported. ^{1 3 4 5 6}

How does this treatment differ from other treatments for opioid use disorder?

This treatment is unique because it uses brain imaging (fMRI) to understand how the brain responds to opioid use and treatment, potentially allowing for more personalized and effective treatment plans compared to standard approaches that do not use such detailed brain activity data. ^{1 2 3 4 5}

What is the purpose of this trial?

This project aims to collect a densely sampled neuroimaging dataset among individuals receiving medications for opioid use disorder (MOUD). MOUD is multiphasic, comprised of medication induction, stabilization, ongoing treatment, and eventual dis-continuation phases. However, with a few small exceptions, existing neuroimaging efforts are almost exclusively single time-point assessments which, by definition, fail to capture these clinically relevant transitions and thus also do not capture individual risk and resilience trajectories. The investigators innovation, the characterization of neurocomputational trajectories during clinically relevant phases of MOUD treatment, will provide unprecedented mechanistic insight into the neurobiological basis of recovery. Once characterized, such trajectories may be used in the identification of specific therapeutic windows for additional intervention (e.g., times of increased neural plasticity) and in the design of novel tailored interventions based on known brain mechanisms (e.g., behavioral therapy, neurostimulation, neurofeedback).

Research Team

Sarah Yip, PhD, MSc

Principal Investigator

Yale University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Ireland 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. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Functional neuroimaging for addiction medicine: From mechanisms to practical considerations. [2017]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Cue-elicited craving in heroin addicts at different abstinent time: an fMRI pilot study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Structural MRI and functional connectivity features predict current clinical status and persistence behavior in prescription opioid users. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Impaired frontostriatal functional connectivity among chronic opioid using pain patients is associated with dysregulated affect. [2021]