Brain Imaging for Opioid Use Disorder

Overseen By Madeline Vincent

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must be taking: Buprenorphine

Must not be taking: Substances interfering

Disqualifiers: Schizophrenia, Bipolar, Stroke, others

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

Compensation: Varies

Number of Visits: 2

315 Participants Needed

Trial Summary

What is the purpose of this trial?

The way people process and remember information may be related to adverse childhood experiences and Opioid Use Disorder symptoms. The purpose of this project is to examine brain function and performance during learning and memory tasks in adults. The study will compare measures of learning and memory across three groups of participants: those with an Opioid Use Disorder (OUD) that take buprenorphine for opioid replacement therapy, adults without an Opioid Use Disorder taking buprenorphine, and healthy adults that do not have an Opioid Use Disorder and are not taking buprenorphine.

Will I have to stop taking my current medications?

The trial allows participants to stay on a stable dose of commonly prescribed psychiatric medications and some sleep aids if they have been on them for more than 3 months. However, any substances or prescription medications that could interfere with the study measures are not allowed.

What data supports the effectiveness of the treatment Computer Tasks for opioid use disorder?

Research shows that brain imaging can help understand how people with opioid use disorder react to drug-related cues, which can predict treatment response. This suggests that computer tasks designed to change how the brain responds to these cues might be effective in treating opioid use disorder. ^{1 2 3 4 5}

Is brain imaging for opioid use disorder safe for humans?

The research on brain imaging for opioid use disorder, including studies using fMRI, suggests that these imaging techniques are generally safe for humans. They have been used to study brain activity in both opioid users and healthy individuals without reported safety concerns. ^{1 6 7 8 9}

How does the treatment 'Computer Tasks' differ from other treatments for opioid use disorder?

The 'Computer Tasks' treatment is unique because it involves using brain imaging to understand and potentially modify brain activity related to opioid use disorder, rather than relying on medication. This approach focuses on identifying and altering neural patterns associated with addiction, which could lead to personalized treatment strategies. ^{1 4 6 10 11}

Research Team

Elizabeth Duval

Principal Investigator

University of Michigan

Eligibility Criteria

This study is for adults with Opioid Use Disorder (OUD) on buprenorphine therapy, those without OUD but taking buprenorphine, and healthy adults without OUD or buprenorphine treatment. Participants should have a history that may include adverse childhood experiences.

Inclusion Criteria

My vision and hearing are normal, or corrected to be normal.

Able to give informed consent

Right handed

Exclusion Criteria

I am not on medications that could affect the study's tests.

Actively suicidal

Contraindication for MRI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo initial assessments including computer tasks to measure memory performance

1 day

1 visit (in-person)

MRI Task Visit

Participants undergo MRI scans to measure BOLD signal and hippocampal connectivity

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any delayed effects or additional data collection

4 weeks

Treatment Details

Interventions

• Computer Tasks

Trial Overview The trial examines how the brain functions during learning and memory tasks in relation to adversity in childhood and opioid use. It involves computer tasks and MRI scans to compare brain activity across three different participant groups.

Participant Groups

Group I: Opioid use disorder (OUD) group Experimental Treatment 2 Interventions

This group takes buprenorphine and has OUD.

Group II: Healthy Controls group Experimental Treatment 2 Interventions

This group does not take BUP and does not have OUD.

Group III: Buprenorphine (BUP) control group: Experimental Treatment 2 Interventions

This group takes BUP and does not have OUD.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

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]

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]

In a study of 27 individuals with opioid use disorder (OUD), effective connectivity analysis revealed that the left anterior cingulate cortex (ACC) to right hippocampus showed the most significant changes when participants were exposed to opioid-related cues, indicating a strong neural response to these cues.

This increased connectivity was positively correlated with attentional bias, suggesting that the brain's response to opioid cues may influence the likelihood of relapse in individuals with OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder. Ma, L., Steinberg, JL., Bjork, JM., et al.[2021]

A study involving 53 individuals with opioid use disorder used fMRI and connectome-based predictive modeling to identify a distinct brain network associated with opioid abstinence, highlighting the importance of specific neural connections in treatment outcomes.

The identified opioid abstinence network showed different connectivity patterns compared to a cocaine abstinence network, suggesting that tailored treatment approaches could be developed based on these unique neural mechanisms to improve recovery from opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling. Lichenstein, SD., Scheinost, D., Potenza, MN., et al.[2022]

In a study involving 14 heroin-dependent patients, acute heroin use was linked to decreased blood flow in the brain's fronto-temporal areas, suggesting immediate negative effects on cerebral perfusion.

The research found a significant positive correlation between gray matter volume and blood flow in frontal regions, indicating that lower gray matter volume is associated with lower perfusion in these areas among heroin users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study. Denier, N., Schmidt, A., Gerber, H., et al.[2021]

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]

Long-term treatment with injectable opioids, specifically diacetylmorphine, over approximately 9 years in 22 patients with opioid use disorder led to significant structural brain changes, including enlargement of the right caudate nucleus, which correlated with the duration of opioid use disorder.

Conversely, reductions in volume were observed in the right amygdala, anterior cingulate cortex, and orbitofrontal cortex, which were associated with opioid dosage and anxiety levels, indicating that long-term opioid treatment affects brain regions involved in addiction and emotional regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain volume changes after long-term injectable opioid treatment: A longitudinal voxel-based morphometry study. Schmidt, A., Vogel, M., Baumgartner, S., et al.[2021]

In a study of 31 mid and late-life adults with major depression who did not fully respond to venlafaxine, low-dose buprenorphine augmentation did not lead to significant neural activation changes compared to placebo over 3 weeks, but both groups showed similar improvements in depressive symptoms.

However, in the buprenorphine group, increased activation in specific brain areas (left anterior insula and bilateral middle frontal gyrus) was linked to greater improvements in dysphoria, suggesting that buprenorphine may uniquely influence certain neural pathways associated with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression. Lin, C., Karim, HT., Pecina, M., et al.[2021]

Noninvasive imaging techniques like PET, fMRI, and MEMRI are crucial for understanding how the brain responds to both acute and chronic opioid exposure, providing insights into the neurobiological mechanisms behind opioid abuse.

A review of 25 studies over 20 years shows that these imaging methods have improved in resolution, allowing researchers to better identify brain regions affected by opioids and understand patterns of brain activation, which is essential for developing effective interventions against opioid misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging of opioid exposure: a review of preclinical animal models to inform addiction research. Kamens, HM., Cramer, S., Hanley, RN., et al.[2023]

Former heroin-dependent individuals (FHD) showed significant reductions in gray matter volume in brain regions associated with visual processing, even after being drug-free for over 3 years, indicating lasting structural brain changes due to addiction.

Functional connectivity analyses revealed that FHD participants had disrupted connections within key brain networks, which correlated with higher impulsivity scores, suggesting that these neural alterations may contribute to ongoing behavioral challenges in recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal gray matter volume and resting-state functional connectivity in former heroin-dependent individuals abstinent for multiple years. Wang, L., Zou, F., Zhai, T., et al.[2022]

Opioid use disorder (OUD) is characterized by significant changes in brain connectivity and function, particularly in the reward system and circuits related to emotion and stress, which contribute to high relapse rates.

Methadone treatment can lead to normalization of brain oscillations within about 6 months for individuals with a long history of opioid use, suggesting potential recovery in cognitive function, although this recovery is not observed in those who remain abstinent without treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resting-State Neuroimaging and Neuropsychological Findings in Opioid Use Disorder during Abstinence: A Review. Ieong, HF., Yuan, Z.[2020]

References

1. 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]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder. [2021]

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

Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Brain volume changes after long-term injectable opioid treatment: A longitudinal voxel-based morphometry study. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Neuroimaging of opioid exposure: a review of preclinical animal models to inform addiction research. [2023]

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

Abnormal gray matter volume and resting-state functional connectivity in former heroin-dependent individuals abstinent for multiple years. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Resting-State Neuroimaging and Neuropsychological Findings in Opioid Use Disorder during Abstinence: A Review. [2020]