Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study

Abstract

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-min 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. It thus appears that 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. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.

Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study

“…Preliminary studies in major depression have also reported that twice-daily rTMS appears feasible, tolerable, and capable of achieving efficacy similar to once-daily rTMS while reducing treatment course length twofold (McGirr et al, 2015;Modirrousta et al, 2018;Schulze et al, 2018). A recent study has also shown accelerated iTBS as a treatment for cocaine use disorder (Steele et al, 2019). However, no trials have been published to date that explore the feasibility and clinical effects achieved with accelerated (twice-daily) TBS approaches in methamphetamine-dependent patients.…”

Transcranial Magnetic Stimulation as an Interventional Tool for Addiction

“…Specifically, researchers are diligently working to understand the mechanisms of change induced by rTMS and the effects related to inherent individual differences in patient populations. Also, there is growing evidence that an engaged circuit is beneficial toward positive outcomes (e.g., VR in Stramba-Badiale et al, 2020) and cocaine cues in Steele et al (2019).…”

“… Steele et al (2019). applied accelerated iTBS treatment to the left-dlPFC in cocaine users while they viewed cocaine cues to engage the targeted circuit.Participants reported reduced use (both amount and frequency) 1-month post-treatment.…”

Transcranial Magnetic Stimulation Meets Virtual Reality: The Potential of Integrating Brain Stimulation With a Simulative Technology for Food Addiction

“…Both rTMS and transcranial direct stimulation (tDCS) have been primarily applied to patients suffering from depression reporting successful enhancement of mood (Wassermann and Zimmermann, 2012;Shin et al, 2015). Transcranial magnetic stimulation has also been employed as a promising alternative to pharmacological therapies, for several other psychiatric disorders which appear to be drug-resistant/non-responsive to medications including bipolar disorder (Xia et al, 2008), schizophrenia (Shi et al, 2014), obsessive-compulsive disorder (Berlim et al, 2013), anxiety disorder (Dilkov et al, 2017), panic disorder (Mantovani et al, 2013), post-traumatic stress disorder (Watts et al, 2012), and addiction disorder (Diana et al, 2017;Hauer et al, 2019;Steele et al, 2019).…”

“…Transcranial magnetic stimulation (TMS) might be effective in modulating circuits and networks implicated in neuropsychiatric disorders and in treating addictions, such as nicotine craving/consumption and cocaine use disorder (Diana et al, 2017;Su et al, 2017;Ma et al, 2019;Steele et al, 2019).…”