Neuropharmacological Imaging for Addiction

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Yihong Yang, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Psychoactive, Vascularly active

Disqualifiers: Pregnancy, Metallic implants, Major psychiatric, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Background: - Functional and structural magnetic resonance imaging (MRI) techniques have allowed researchers to map and study how the brain works when at rest and when engaged in specific tasks. MRI scans have provided more information about how drugs affect the brain, and about how drug addiction changes the brain and influences behavior, mood, and thinking processes. To better understand the underlying mechanism of drug addiction and to develop strategies for more effective treatment, researchers are interested in developing new MRI techniques to study the effects of addiction on the brain. Objectives: - To develop new functional and structural MRI techniques, and to evaluate their potential use in brain imaging studies related to addiction. Eligibility: * Individuals between 18 and 80 years of age. * Participants may be smokers or nonsmokers, and may use drugs or not use drugs. Design: * During the initial screening, participants will complete questionnaires about family and personal history, drug use, and other information as required by the researchers. Participants who will be asked to complete tasks during the MRI scan will be shown how to perform these tasks before the scanning session. * Before each study session, participants may be asked to complete some or all of the following: questions about their drug use during the last week, a breathalyzer test, a urine drug-use assessment, a urine pregnancy test, or a measure of carbon monoxide. Participants will also provide blood samples before the start of the scan. * For each scanning session, participants will have an MRI scan that will last approximately 2 hours. * MRI scans may include specific tasks to be performed during the scan, or an experiment that studies the brain's response to carbon dioxide....

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using psychoactive or vascularly active medications, you might need to discuss this with the researchers, as these could affect certain MRI techniques.

What data supports the effectiveness of this treatment for addiction?

The use of magnetic resonance imaging (MRI) has been crucial in addiction research, helping to map brain changes related to addiction and linking neurobiology to behavior. This suggests that MRI technology, like the Magnetom Prisma Fit 3T Scanner, could be effective in understanding and potentially treating addiction.

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Is the Magnetom Prisma Fit 3T Scanner safe for use in humans?

The Magnetom Prisma Fit 3T Scanner is generally considered safe for use in humans, as studies show that exposure levels to magnetic fields are within safe limits for occupational exposure. However, caution is advised for patients with certain implanted devices, as they may experience discomfort or harm during scanning.

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How is the Magnetom Prisma Fit 3T Scanner treatment unique for addiction?

The Magnetom Prisma Fit 3T Scanner is unique for addiction treatment because it uses advanced MRI technology to map brain activity and understand the neurobiological aspects of addiction, which can help tailor more effective treatments. Unlike traditional therapies, this approach focuses on visualizing brain changes and linking them to behavior, offering a non-invasive way to study addiction.

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Eligibility Criteria

Adults aged 18-80, including smokers and non-smokers, drug users and non-users. Participants must be able to consent and understand English. Exclusions include pregnancy, metal implants that affect MRI safety, high seizure risk conditions, severe psychiatric or neurological disorders, major medical illnesses like heart disease or diabetes.

Inclusion Criteria

All subjects must be able to provide informed consent

I am an adult between 18 and 80 years old and if female, not pregnant.

Exclusion Criteria

Subjects with neurological illnesses severe enough to impact data being gathered

Pregnant individuals

Subjects unable to undergo MRI scanning due to implanted metallic devices or claustrophobia

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

MRI Methodology Development and Evaluation

Participants undergo MRI scans for methodology development and evaluation, including pulse sequence development, testing, and parameter optimization.

Up to 4 visits, each visit up to 4 hours

Up to 4 visits (in-person)

TMS-fMRI Experiment

Participants undergo TMS-fMRI scans to evaluate the relationship between BOLD activation and MEP, establishing a BOLD activation marker of cortical excitability.

6-8 hours

1 visit (in-person)

TRPMS Experiment

Participants undergo TRPMS sessions to evaluate the prolonged effect on motor cortex excitability and cortical excitability changes measured with simultaneous TMS-fMRI.

2-6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the experimental sessions.

4 weeks

2 visits (in-person)

Participant Groups

The trial is developing new MRI techniques for addiction studies. It involves an initial screening with questionnaires followed by a series of MRI scans lasting about 2 hours each. Some scans may require tasks or study the brain's response to carbon dioxide.

Group I: TRPMS Experiment 2 Experimental Treatment 2 Interventions

To evaluate cortical excitability changes caused by TRPMS measured with simultaneous TMS-fMRI. Participants will undergo a baseline TMS/fMRI session to get a measurement of baseline cortical excitability in the form of single-pulse TMS induced BOLD activation and determine motor hot-spot and RMT. We will then conduct an event-related single-pulse TMS/fMRI session with TMS stimulus at 120% RMT, 50 events with jittered inter-stimulus-interval (ISI) averaging 16s. Simultaneous EMG recording will be gathered from the corresponding hand muscle. Next we will use TRPMS to stimulate the left motor cortex over the hot-spot : 20-min application of TRPMS, 100ms duration, 0.2Hz (one stimulus every 5s), total 240 stimuli. Then we will evaluate the modulatory effect of the TRPMS stimulation via a second TMS/fMRI session with a similar procedure as the baseline session using the RMT determined at baseline. Total time for this experiment is about 5-6 hours.

Group II: TRPMS Experiment 1 Experimental Treatment 1 Intervention

To evaluate the prolonged effect of TPRMS on motor cortex excitability and help interpret and design subsequent experiments investigating the effect of TRPMS on BOLD signal. The experiment design consists of four groups, each group will include 10 participants (8 completers/group). For TRPMS stimulation sessions, our test conditions will be a 10 stimuli-session (approximately 2min), 50 stimuli-session (approximately 7min), 100 stimuli-session (approximately 14min), and 150 stimuli-session (20min) for each of the four groups, respectively. Therefore, the outcome will be measured with the spontaneous motor unit potentials (sMUPs) in the contralateral abductor pollicis brevis muscle (APB). After the stimulation session, we will measure sMUPs continuously for another 20min to observe the prolonged effect of the TRPMS stimulation and to compare these four conditions. The total approximate time required for this experiment is about 2-2.5 hours.

Group III: TMS-fMRI Experiment 1 Experimental Treatment 2 Interventions

To evaluate the relationship between BOLD activation and MEP and establish a BOLD activation marker of cortical excitability. Participants will start with a set of two short task-based EPI scans and anatomical scan. RMT will then be determined. Participants will undergo a single-pulse TMS-fMRI scan with stimulation intensities relative to the RMT over the motor cortex and/or the DLPFC. In total, six (6) intensities will be tested, 80% 100%, 105%, 110%, 115%, and 120% relative to the RMT. The fMRI design will be event-related. Each intensity (event type) will be presented 50 times. The order of the intensities will be randomized, and the inter-stimulus-interval (ISI) will range from 12s to 20s (centered at 16s plus random jittering in between, about 0.06Hz). The highest intensity of stimulation will be 120% RMT. EMG recordings in the corresponding hand muscle will be simultaneously acquired during the scan. Total approximate time required for this experiment is about 6-8 hours.

Group IV: MR Methodology Development and Evaluation Experimental Treatment 2 Interventions

Methodology development and evaluation consists of pulse sequence development, testing, and parameter optimization. For each method we develop or evaluate, we may recruit up to 40 participants to come in for up to 4 visits each. Each participant will be scanned for up to 2 sessions per visit, not to exceed 4 total scan hours per visit.

Magnetom Prisma Fit 3T Scanner is already approved in European Union, United States, Canada, Japan, China for the following indications:

🇪🇺 Approved in European Union as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

🇺🇸 Approved in United States as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

🇨🇦 Approved in Canada as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

🇯🇵 Approved in Japan as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

🇨🇳 Approved in China as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institute on Drug Abuse, Biomedical Research Center (BRC) Baltimore, MD

Georgetown University Washington, United States

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA) Lead Sponsor

References

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The neurobiology of addiction: the perspective from magnetic resonance imaging present and future. [2022] Addiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer.

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How Internet technology can improve the quality of care for substance use disorders. [2019] By allowing for the efficient delivery of instructional content and the secure collection of self-report data regarding substance use and related problems, the Internet has tremendous potential to improve the effectiveness and accessibility of addiction treatment services. This article discusses some of the ways in which Internet technology can facilitate, complement and support the process of traditional clinician-delivered treatment for individuals with substance use disorders. Internet applications are being used to support a range of activities including (a) the assessment and feedback process that constitutes a central feature of brief motivational interventions, (b) the concurrent monitoring of individual level outcomes among patients who are currently enrolled in addiction treatment programs, (c) the continuing care and ongoing recovery of patients who have completed treatment, and (d) the delivery of clinical training in evidence based practices for addiction treatment providers. This emerging body of literature suggests that addiction counselors and program administrators can enhance the quality of clinician-delivered treatment by incorporating internet applications into existing processes of care. Internet applications provide an unparalleled opportunity to engage patients in the treatment process, incorporate real-time data into treatment planning, prevent relapse, and promote evidence-based treatment approaches.

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Positron emission tomography and single-photon emission computed tomography in substance abuse research. [2019] Many advances in the conceptualization of addiction as a disease of the brain have come from the application of imaging technologies directly in the human drug abuser. New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) and single-photon emission computed tomography (SPECT) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology, and medicine. This topic cuts across the medical specialties of neurology, psychiatry, oncology, and cardiology because of the high medical, social, and economic toll that drugs of abuse, including the legal drugs, cigarettes and alcohol, take on society. This article highlights recent advances in the use of PET and SPECT imaging to measure the pharmacokinetic and pharmacodynamic effects of drugs of abuse on the human brain.

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Accessory equipment considerations with respect to MRI compatibility. [2019] The MR Section of The National Electrical Manufacturers Association (NEMA), in response to a request from the Food & Drug Administration (FDA), recently issued a position paper to address generic issues related to the compatibility of accessory equipment produced by third party equipment manufacturers or MR equipment users and intended to be used in conjunction with MR equipment or within the MR scanning room. The recommendations concern scanning accessories, such as radiofrequency (RF) coils, patient monitoring equipment and injectors, as well as patient comfort accessories and positioning devices. The following issues related to safety performance are discussed: (a) the interaction of the equipment with the MR scanner, (b) interactions of the MR scanner with the equipment, and (c) potential safety hazards for patients and staff that can be posed by accessory equipment in the MR scan environment. The recommendations are based on combined input from NEMA member companies who manufacture MR systems and MR accessories and are presented for consideration in the design of MR accessory products and incorporation of these concepts into testing plans to ensure MR compatibility of third party devices.

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The effect of magnetic resonance imagers on implanted neurostimulators. [2019] This in-vitro study was designed to investigate the safety of various implanted neurostimulators in magnetic resonance (MR) imagers. The effects of the static and changing magnetic fields and the radio frequency (RF) electromagnetic field generated by 0.35 and 1.5 T MR imagers on the voltage output of four models of implantable passive neurostimulators and two models of implantable self-powered neurostimulators was studied. The neurostimulators were mounted on a support and placed in the imagers. An oscilloscope monitored the voltages at the outputs of the neurostimulators. For an Avery single-channel stimulator, located at the isocenter, the amplitude of the output pulses induced by the 0.35 T imager was 6V; from a 1.5 T imager, it was 12 V. These amplitudes can cause discomfort and possible harm to a patient if the typical therapeutic value is 1-5 V. The amplitude of the stimulator receiver's output decreased to relatively safe values beyond 40 cm from the isocenter. By contrast, there was no significant voltage output from the Medtronic SE-4 receiver. For two models of self-powered neurostimulators, the Medtronic Itrel and the Cordis MK II, the programmed stimulus parameters were not affected by the pulsed magnetic fields of the MR imagers. However, the RF fields at the isocenter heated the metal case of the stimulators. The rotational and linear forces produced by the fixed magnet on the Cordis MK II were judged to be too strong for a patient with this implant to be scanned. The study showed that patients with certain types of implanted neurostimulators can be scanned safely under certain conditions.

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Measurement of the weighted peak level for occupational exposure to gradient magnetic fields for 1.5 and 3 Tesla MRI body scanners. [2016] The purpose of this work is to give a contribution to the construction of a comprehensive knowledge of the exposure levels to gradient magnetic fields (GMF) in terms of the weighed peak (WP), especially for 3 Tesla scanners for which there are still few works available in the literature. A new generation probe for the measurement of electromagnetic fields in the range of 1 Hz-400 kHz was used to assess the occupational exposure levels to the GMF for 1.5 and 3.0 Tesla MRI body scanners, using the method of the WP according to the International Commission on Non-Ionizing Radiation Protection (ICNIRP) approach. The probe was placed at a height of 1.1 m, close to the MRI scanners, where operators could stay during some medical procedures with particular issues. The measurements were performed for a set of typical acquisition sequences for body (liver) and head exams. The measured values of WP were in compliance with ICNIRP 2010 reference levels for occupational exposures.

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PET imaging in clinical drug abuse research. [2019] Over the last two decades, SPECT (single photon emission computed tomography) and especially PET (positron emission tomography) have proven increasingly effective imaging modalities in the study of human psychopharmacology. Abusing populations can be studied at multiple times after abstinence begins, to give information about neurochemical and physiological adaptations of the brain during recovery from addiction. Individual human subjects can be studied using multiple positron labeled radiotracers, so as to probe more than one facet of brain function. PET and SPECT have been used to help our understanding of many aspects of the pharmacokinetics and pharmacodynamics of abused drugs, and have made valuable contributions in terms of drug mechanisms, drug interactions (e.g. cocaine and alcohol) and drug toxicities. They have also been employed to study the acute effects of drugs on populations of active drug abusers and of normal controls, and to evaluate the neurochemical consequences of candidate therapies for drug abuse. A particularly productive strategy has been the use of PET in conjunction with neuropsychological testing of subjects, to allow correlation of imaging data with uniquely human aspects of the effects of drugs, such as euphoria and craving.

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Opioid imaging. [2022] Many breakthrough scientific discoveries have been made using opioid imaging, particularly in the fields of pain, addiction and epilepsy research. Recent developments include the application of ever higher resolution whole-brain positron emission tomography (PET) scanners, the availability of several radioligands, the combination of PET with advanced structural imaging, advances in modeling macroparameters of PET ligand binding, and large-scale statistical analysis of imaging datasets. Suitable single-photon emission computed tomography (SPECT) tracers are lacking, but with the increase in the number of available PET (or PET/CT) cameras and cyclotrons thanks to the clinical successes of PET in oncology, PET may become widespread enough to overcome this limitation. In the coming decade, we hope to see a more widespread application of the techniques developed in healthy volunteers to patients and more clinical impact of opioid imaging.