Accelerated Intermittent Theta-Burst Stimulation for Opiate Use Disorder

The proposed study aims to investigate the effectiveness of aiTBS applied to either the
L-DLPFC or the ACC for reducing SI in individuals with OUD and identify neural functional
connectivity changes underlying treatment response. 30 individuals with OUD who endorse
suicidal ideation will be recruited. The accelerated iTBS treatment will involve 10 daily
sessions of iTBS. Stimulation will be delivered to either the ACC or the L-DLPFC for 5
consecutive days. Suicidal ideation, depressive symptoms and opiate misuse will be measured
before and after the 5-day stimulation course. Functional magnetic resonance imaging (fMRI)
scans will also be carried out before and after stimulation to examine aiTBS-induced changes
in neural functional connectivity. Changes in suicidal ideation, depressive symptoms and
opiate misuse will be measured using both clinician-rated and self-report assessments.

Inclusion Criteria:

1. Over 18 at the time of screening

2. Able to read, understand, and provide written, dated informed consent prior to
screening. Participants will be deemed likely to comply with study protocol and
communicate with study personnel about adverse events and other clinically important
information.

3. Diagnosed with Opiate Use Disorder, according to the criteria defined in the Diagnosis
and Statistical Manual of Mental Disorders.

4. Endorse suicidal ideation (score >2 on the SSI-C).

5. Not in a current state of mania or psychosis (Young Mania Rating Scale)

6. In good general health, as ascertained by medical history.

7. If female, a status of non-childbearing potential or use of an acceptable form of
birth control per the following specific criteria:, a. Non-childbearing potential
(e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized
(status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her
last menses at least one year prior to screening); or, b. Childbearing potential, and
meets the following criteria. Childbearing potential, including women using any form
of hormonal birth control, on hormone replacement therapy started prior to 12 months
of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship
with a partner who has had a vasectomy, or is sexually abstinent. ii. Negative urinary
pregnancy test at screening, confirmed by a negative urinary pregnancy test at
randomization prior to receiving study treatment. iii. Willing and able to
continuously use one of the following methods of birth control during the course of
the study, defined as those which result in a low failure rate (i.e., less than 1% per
year) when used consistently and correctly: implants, injectable or patch hormonal
contraception, oral contraceptives, IUD, double-barrier contraception, sexual
abstinence. The form of birth control will be documented at screening and baseline.

8. Clear urine drugs test

9. Registered with a psychiatrist

10. On stable psychotropic medication or psychotherapy for at least 6 weeks prior to the
study with plans to continue throughout study enrollment.

11. Failed at least one anti-depressant trial (>/=6 week duration at an effective dose)

12. Ability to tolerate clinical study procedures.

13. No contraindications for TMS or MRI

Exclusion Criteria:

1. Any abnormalities indicated on the MRI e.g. structural neurological condition, more
subcortical lesions than would be expected for age, stroke effecting stimulated area
or connected areas or any other clinically significant abnormality that might affect
safety, study participation, or confound interpretation of study results.

2. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear

3. History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)

4. Shrapnel or any ferromagnetic item in the head.

5. Pregnancy

6. Autism Spectrum disorder

7. Any current or past history of any physical condition which in the investigator's
opinion might put the subject at risk or interfere with study results interpretation.

8. Active substance use (<1 week) or intoxication verified by toxicology screen--of
cocaine, amphetamines, benzodiazepines

9. Cognitive impairment (including dementia)

10. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)

11. Current mania

12. Current unmanageable psychosis

13. Showing symptoms of withdrawal from alcohol or benzodiazepines

14. IQ<70

15. Movement disorder

16. Any other indication the PI feels would comprise data.

17. Motor threshold value which does not enable treatment