Neurocircuit Strategy to Decrease Cocaine Cue Reactivity

Study Overview
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Brief Summary
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The overarching goal of this project is to examine the effect of combining theta burst stimulation (TBS) and N-acetylcysteine (NAC) on cocaine craving and brain response to cocaine-related images.

Official Title
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Neurocircuit Strategy to Decrease Cocaine Cue Reactivity

Conditions
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Cocaine-Related Disorders

Intervention / Treatment
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* Drug: N-acetylcysteine
* Device: Theta-burst stimulation (TBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18-65 2. English fluency 4. Meet criteria for cocaine use disorder (CUD), as determined by DSM-V criteria, using the Structured Clinical Interview for DSM-V. 5. Enrolled in an intensive outpatient treatment program (MUSC Center for Drug and Alcohol Programs Intensive Outpatient Program (CDAP-IOP) or currently engaged in treatment for substance related problems. 6. Able to read and understand questionnaires and informed consent 7. Lives within 50 miles of the study site. 8. Is not at elevated risk of seizure (i.e., does not have a history of seizures, is not currently prescribed medications known to lower seizure threshold) 9. Does not have metal objects in the head/neck. 10. Does not have a history of traumatic brain injury, including a head injury that resulted in hospitalization, loss of consciousness for more than 10 minutes, or having ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage. 11. Does not have a history of claustrophobia leading to significant clinical anxiety symptoms. Exclusion Criteria: Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases Any physical or intellectual disability affecting completion of assessments Any contraindication to MRI Current or past psychosis ECT in last 6 months Among females, pregnancy at screening will be exclusionary. Females of child bearing potential must agree to undergo a pregnancy test 72 hours prior to the fMRI scanning session and regularly before and during the medication trial. They must further agree to notify the study physician or PA if they become pregnant during the study. Clinical Institute Withdrawal Assessment (CIWA-Ar) scale will be used to assess alcohol withdrawal. Individuals with CIWA > 8 will be excluded. Individuals with unstable medical illness (e.g., hypertension, diabetes, myocardial infarction) Has current suicidal ideation or homicidal ideation. Has the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD Suffers from chronic migraines Any physical or intellectual disability affecting completion of assessments

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine + Theta Burst Stimulation<br> | Drug: N-acetylcysteine<br>* N-acetylcysteine (NAC) is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with cystic fibrosis or chronic obstructive pulmonary disease. It has a long-established safety record in adults and children, with FDA approval since 1963. The side effects most commonly noted in people who take NAC by mouth include diarrhea, nausea, vomiting, and headache. These side effects are usually mild and go away even with continued use of NAC by mouth. There is also a risk of a skin reaction, such as flushing, itching, or rash. A meta-analysis of studies evaluating long-term oral treatment with NAC for prevention of chronic bronchitis found that NAC was well tolerated, with generally mild, most commonly gastrointestinal adverse effects that did not require treatment interruption.<br>* Other names: NAC;Device: Theta-burst stimulation (TBS)<br>* Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.<br>|
| Sham Comparator: N-acetylcysteine + Sham Theta Burst Stimulation<br> | Drug: N-acetylcysteine<br>* N-acetylcysteine (NAC) is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with cystic fibrosis or chronic obstructive pulmonary disease. It has a long-established safety record in adults and children, with FDA approval since 1963. The side effects most commonly noted in people who take NAC by mouth include diarrhea, nausea, vomiting, and headache. These side effects are usually mild and go away even with continued use of NAC by mouth. There is also a risk of a skin reaction, such as flushing, itching, or rash. A meta-analysis of studies evaluating long-term oral treatment with NAC for prevention of chronic bronchitis found that NAC was well tolerated, with generally mild, most commonly gastrointestinal adverse effects that did not require treatment interruption.<br>* Other names: NAC;|
| Experimental: Placebo + Theta Burst Stimulation<br> | Device: Theta-burst stimulation (TBS)<br>* Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.<br>|
| No Intervention: Placebo + Sham Theta Burst Stimulation<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of change in fMRI brain response to images from TBS | Measure the effects of neural stimulation on MRI brain response to drug-related cues | 5 weeks | 
| Magnitude of change in brain functional connectivity | Measure the effects of N-Acetylcysteine on MRI brain functional connectivity | 5 weeks | 
| Magnitude of change in fMRI brain response to images from NAC | Measure the combined effects of neural stimulation and N-Acetylcysteine on brain response to drug-related cues. | 5 weeks |