The Therapeutic Potential of Transcranial Magnetic Stimulation in Addiction

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.

Dopamine system plays a pivotal role in specific kinds of substance use disorders (SUD, i. e., cocaine and methamphetamine use disorders). Many studies addressed whether dopamine-involved craving could be alleviated by non-invasive brain stimulation (NIBS) techniques. Nevertheless, the outcomes were highly inconsistent and the stimulating parameters were highly variable. In the current study, we ran a meta-analysis to identify an overall effect size of NIBS and try to find stimulating parameters of special note. We primarily find 2,530 unduplicated studies in PubMed, Psychology and Behavioral Sciences Collection, PsycARTICLES, PsycINFO, and Google Scholar database involving “Cocaine”/“Amphetamine”/“Methamphetamine” binded with “TMS”/“tDCS”/“non-invasive stimulation” in either field. After visual screening, 26 studies remained. While 16 studies were further excluded due to the lack of data, invalid craving scoring or the absence of sham condition. At last, 16 units of analysis in 12 eligible studies were coded and forwarded to a random-effect analysis. The results showed a large positive main effect of stimulation (Hedge's g = 1.116, CI = [0.597, 1.634]). Further subgroup analysis found that only high-frequency repetitive transcranial magnetic stimulation (rTMS) could elicit a significant decrease in craving, while the outcome of low-frequency stimulation was relatively controversial. Moreover, univariate meta regression revealed that the number of pulses per session could impose negative moderation toward the intervention. No significant moderation effect was found in types of abuse, overall days of stimulation and other variables of stimulating protocol. In conclusion, this meta-analysis offered a persuasive evidence for the feasibility of using NIBS to remit substance addictive behavior directly based on dopamine system. We also give clear methodological guidance that researchers are expected to use high-frequency, sufficiently segmented rTMS to improve the efficacy in future treatments.