We will evaluate the effects of deep brain stimulation (DBS) of bilateral nucleus accumbens (NAc) added to background treatment for treatment refractory Methamphetamine Use Disorder (MUD). This is a small randomized cross-over study to demonstrate feasibility and safety, test treatment outcomes (use, craving), and identify novel biological targets (NAc local field potentials (LFP) and functional MRI).

In a randomized cross-over design of DBS of the nucleus accumbens (NAc) for treatment refractory methamphetamine use disorder (MUD, n=5), we will test safety, feasibility, effect on clinical outcomes (craving and use), and seek to identify biological targets (using cue craving during recording of local field potentials and MRI).

Inclusion Criteria:

Adults (men and non-pregnant or nursing women) between 22-65 years of age will be eligible for enrollment, if meeting the following criteria:

1. Current diagnosis of DSM-5 MUD (with past year specifier of severe and at least a 5-year history);
2. Failed at least 2 prior treatment episodes (defined as outpatient or inpatient, utilizing a previously validated psychosocial treatment for addiction such as cognitive behavioral therapy, contingency management, motivational interviewing (Stuart et al., 2019) and not counting episodes with only detoxification) for MUD, with at least 1 episode having been residential;
3. Provides a urine drug screen positive for mAMP;
4. Endorses at least 10 days of mAMP use in the past month;
5. Able to complete 1 week of inpatient detoxification prior to surgery and 4 weeks of inpatient treatment following surgery;
6. No change in current psychiatric medication regimen, or medication free, for at least 4 weeks prior to entry;
7. Able to provide informed consent;
8. Able to comply with all testing and follow-up requirements as defined by study protocol (including providing a home address and two local collateral contacts);
9. Medically able to undergo DBS procedure as assessed by Study Neurosurgeon;
10. Has platelet count, PT and PTT within normal laboratory limits;
11. Adequate English proficiency for study consent, and completion of the study instruments;
12. Reside in the state of Colorado.

Exclusion Criteria:

1. Lifetime non-substance-induced psychotic disorders, schizophrenia, or schizoaffective disorder defined by DSM-5;
2. Current diagnosis of DSM-5 drug use disorder other than stimulant, alcohol, cannabis or nicotine use disorder;
3. Non-substance-induced manic episode within the past 3 years or major depressive episode in the past year;
4. Current clinically significant neurological disorder or medical illness;
5. Presence of a clinically significant abnormality on preoperative MRI;
6. Inability to have an MRI;
7. Inability to undergo general anesthesia required for tunneling of extension cable and placement of the batteries;
8. Pregnancy or lack of use of effective contraception in women of childbearing age, as assessed by urine pregnancy test and self-report (participants will consent to continue effective contraceptives during the study);
9. Coagulopathy, as determined by PT, PTT, platelet count, and medical history;
10. History of recurrent infections;
11. Inability to adhere to the requirements of the study;
12. Imminent risk of suicide as determined by Study Psychiatrist's assessment and investigators' clinical judgment or past-year suicide attempt, any positive response on baseline Columbia Suicide Severity Scale or history of parental completed suicide;
13. Active criminal justice involvement (i.e., any unresolved legal problems that could jeopardize continuation or completion of the study);
14. History of head injury with loss of consciousness for more than 15 minutes, neurological illness (including primary seizure disorder);
15. Diagnosis of dementia;
16. Conditions requiring diathermy.

Participants and all study personnel are blinded to subject assignment except the physician completing DBS programming.