Effects of Non-invasive Brain Stimulation on Stimulant Craving in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-Analysis

Abstract

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.

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

“…even when faced with consequences, subjects continue to pursue the drug) (Hu et al, 2019), the possibility of using rTMS to stimulate hypoactive prefrontal cortical neurons, which can then modulate interconnected networks, is appealing (Diana et al, 2017;Madeo and Bonci, 2019;Song et al, 2019). An increasing number of studies have shown anticraving effects following rTMS treatment targeting the PFC (see Ma et al, 2019;Madeo and Bonci, 2019;Zhang et al, 2019), presumably through modulation of the efferent glutamatergic and afferent dopaminergic connections (Diana, 2011;Diana et al, 2017; Figure 1). Therefore, rTMS modulation of mesocorticolimbic pathways in people with substance use disorders may provide therapeutic effects.…”

“…In clinical studies, HF-rTMS over the DLPFC has been shown to have anticraving effects (for an overview, see Ma et al, 2019). Most studies apply chronic stimulation (i.e.…”

“…Need for Consistency and Scientific Rigor Current drawbacks of clinical studies, which have also been pointed out by recent reviews, include the lack of follow-ups after treatment and the lack of sham-controls in some studies (Ma et al, 2019;Madeo and Bonci, 2019;Zhang et al, 2019). Clinical studies should include follow-up measurements, sham-controls, and greater consistency of stimulation parameters between studies.…”

Transcranial Magnetic Stimulation as an Interventional Tool for Addiction

“…Gambling disorder has similar behavioral and pathophysiological manifestations as SUDs, suggesting potential overlap in dysregulation and interventional tools for treatment. In treating SUDs with rTMS, these reviews highlight the importance of considering both dopamine and glutamate (Moretti et al, 2020) as well as assessing individual differences in patients (Ma et al, 2019) to better uncover the known unknown of the underlying mechanisms of rTMS interventions. Also, applying high frequency stimulation (∼5-20 Hz) is more effective than low frequency (∼1 Hz) at reducing craving post-rTMS (Ma et al, 2019).…”

“…In treating SUDs with rTMS, these reviews highlight the importance of considering both dopamine and glutamate (Moretti et al, 2020) as well as assessing individual differences in patients (Ma et al, 2019) to better uncover the known unknown of the underlying mechanisms of rTMS interventions. Also, applying high frequency stimulation (∼5-20 Hz) is more effective than low frequency (∼1 Hz) at reducing craving post-rTMS (Ma et al, 2019). This reflects the shift toward implementing the high frequency, and shorter to implement, continuous and intermittent theta-burst stimulation (c/iTBS) protocols (Huang et al, 2005) than other rTMS protocols.…”