Transcranial Direct Current Stimulation to Modulate Top-Down Regulation for Drug Craving in Methamphetamine Use Disorder

Methamphetamine use disorder (MUD) is among the costliest and deadliest substance use
disorders (SUDs) world-wide and is frequently comorbid with other mental health conditions.
There is no empirically validated medical treatment for MUD. Drug craving is the signature
aspect of MUD and other substance use disorders and has been associated with continued drug
use and relapse. The investigators and others have shown that transcranial direct current
stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC) can modulate drug craving in
different SUDs. tDCS is a method of non-invasive brain stimulation and is a low-cost scalable
technology without any serious side effects that delivers low levels of direct current (0.1-2
mAmp) transcranially. However, there are significant inter-individual differences in response
to tDCS, which is not well understood but can have profound impact on efficacy. Meanwhile,
there are no studies with neuroimaging to show how tDCS affects drug craving. The
investigators propose the first combined tDCS/functional Magnetic Resonance Imaging (fMRI)
study to examine the acute effects of tDCS on neural substrates underlying drug induced
craving. The investigators hypothesize that tDCS amplifies DLPFC's top-down modulatory role
via its connectivity to other cortical-subcortical areas. In this double blind randomized
experimental design, the investigators will recruit 60 people with MUD during their early
abstinence phases into parallel arms with active and sham DLPFC tDCS. Each subject will
undergo resting state and task based (drug cue exposure paradigm) functional MRI pre and post
tDCS. The investigators will conduct individual difference analyses to explore the potential
predictors for tDCS response, including pre-tDCS top-down connectivity measures of DLPFC and
other subjective, clinical, behavioral, structural, and functional variables. The results of
this study will provide neuroscience-based evidence for the efficacy of tDCS and will advance
the field towards precision addiction medicine.

Inclusion Criteria:

1. English speaking.

2. Diagnosed with Methamphetamine Use Disorder (last 12 months) based on the Mini
International Neuropsychiatric Interview (MINI) interview (Diagnostic and Statistical
Manual of Mental Disorders-DSM-5)

3. Being abstinent from methamphetamine in an addiction treatment program for at least
one week based on medical records or self-report

4. Positive response to Methamphetamine cue-reactivity screening (MCS)

5. Willing and capable of interacting with the informed consent process

Exclusion Criteria:

1. Unwillingness or inability to complete any of the major aspects of the study protocol,
including magnetic resonance imaging (i.e., due to claustrophobia), drug cue rating,
or behavioral assessment.

2. Abstinence from methamphetamine for more than 6 months based on self-report

3. Schizophrenia or bipolar disorder based on the MINI interview

4. Active suicidal ideation with intent or plan determined by self-report or assessment
by PI or study staff during the initial screening or any other phase of the study

5. Positive drug test for amphetamines, opioids, cannabis, alcohol,Phencyclidine (PCP),
or cocaine confirmed by breath analyzer and urine tests

6. Any active skin disorder that affects skin integrity of the scalp

7. Having any condition that would preclude undergoing an fMRI scan or tDCS stimulation
based on the fMRI safety and tDCS safety checklists

8. Unstable medical disorder reported in subject's medical history or by a clinician
assessment

9. History of seizure

10. Non-correctable vision or hearing problems.

11. Any other condition the PI or study staff feel would put the subject at risk for
entering the study