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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01147

Accelerated intermittent theta-burst stimulation as a treatment for cocaine use disorder: A proof-of-concept study

  • 1National Institute on Drug Abuse (NIDA), United States
  • 2Center on Compulsive Behaviors, National Institutes of Health, United States

There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-minute interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. Accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use.

Keywords: Cocaine use disorder, Intermittent theta-burst stimualtion, Open-label, Accelerated iTBS, Dorsolateral prefrontal cortex (DLFPC)

Received: 15 Jul 2019; Accepted: 11 Oct 2019.

Copyright: © 2019 Steele, Maxwell, Ross, Stein and Salmeron. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Betty Jo Salmeron, National Institute on Drug Abuse (NIDA), Bethesda, United States,