Cocaine use disorder (CUD) is a difficult-to-treat condition with no FDA-approved medications. Recent work has turned to brain stimulation methods to help rectify hypofrontality and dopamine reward system changes often observed in individuals with CUD. Preliminary studies using transcranial magnetic stimulation (TMS) have demonstrated promising results, but there is room for optimization of the stimulation site, stimulation pattern, and identification of relevant biomarkers of TMS effects. The current pilot study aimed to test the feasibility, safety, and preliminary effects of a double-blind, sham-controlled, cross-over, acute design using intermittent theta burst stimulation to dorsomedial prefrontal cortex (dmPFC) on electroencephalogram (EEG) as intermediate outcome assessment in CUD patients. This small pilot enrolled five individuals with moderate-to-severe CUD for feasibility and proof-of-concept. Participants completed safety, psychometric, and EEG measures before and after receiving two sessions of active or sham TMS to dmPFC on two separate days. All five participants completed all the study tasks and found the TMS to be tolerable. The side effects were minimal and consistent with an acute TMS design. Visible changes were observed in the electrical activity of the brain during a monetary guessing task, while minimal changes in psychometric measures were observed. These results indicate the feasibility and safety of the current approach and suggest that dmPFC is a viable target for treating CUD. Future work should expand upon these findings in a randomized controlled clinical trial.

JQ has a clinical research support relationship with LivaNova; is a member of the speaker bureau with Myriad Neuroscience and AbbVie; is a consultant for EMS, Libbs, and Eurofarma; is a stockholder at Instituto de Neurociencias Dr. Joao Quevedo; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press.

NCT05631548

This study was funded by the UTHealth Houston Career Development and Research Excellence (CaDRE) Program in Psychiatry. The work by HEW was funded in-part by NIDA K01DA058765.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Committee for the Protection of Human Subjects of the University of Texas Health Science Center at Houston gave ethical approval of this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.