Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: a preliminary study

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) can temporarily interrupt or facilitate activity in a focal brain region. Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can affect processes involved in drug addiction. We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine (MA) when compared to a sham rTMS session.

Methods: In this single-blind, sham-controlled crossover study, 10 non-treatment seeking MA-dependent users and 8 healthy controls were randomized to receive 15 min of sham and real (1 Hz) DLPFC rTMS in two experimental sessions separated by 1h. During each rTMS session, participants were exposed to blocks of neutral cues and MA-associated cues. Participants rated their craving after each cue block.

Results: In MA users, real rTMS over the left DLPFC increased self-reported craving as compared to sham stimulation (17.86 ± 1.46 vs. 24.85 ± 1.57, p=0.001). rTMS had no effect on craving in healthy controls. One Hertz rTMS of the left DLPFC was safe and tolerable for all participants.

Conclusions: Low frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA participants. These preliminary results suggest that 1 Hz rTMS of the left DLPFC may increase craving by inhibiting the prefrontal cortex or indirectly activating subcortical regions involved in craving.

Trial registration: ClinicalTrials.gov NCT01685463.

Keywords: Craving; Dorsolateral prefrontal cortex; Methamphetamine; Transcranial magnetic stimulation.

Conflict of interest statement

Conflict of interest

None of the authors has a conflict of interest to declare.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig. 1

Diagram showing the stimulation and assessments that were performed during this study. M = methamphetamine, O = object.

Fig. 2

Comparisons of cue-induced craving rating between neutral cue and MA cue in the healthy control group and the MA dependent user group on baseline assessment. Mixed model analysis of variance revealed a significant main group (control vs. MA) effect (p < 0.0001) and a significant main cue exposure effect (p < 0.00001). Post hoc t test showed that MA cue exposure induced significant higher subjective cue craving ratings (p < 0.001), while no significant difference was found between neutral and MA cue in control group (p = 0.29). Mean ± SEM; *p < 0.05, **p < 0.01.

Fig. 3

Comparisons of cue-induced craving rating between TMS and sham; neutral cue and MA cue; control group and the MA group. Mixed model analysis of variance showed that the cue craving of MA group was significant higher than control group (p < 0.0000001); MA cue craving was significant higher than neutral cue (p < 0.000001). Although main effect of treatment was not significant (p = 0.14), post hoc results showed that the cue craving during TMS was significant higher than that during sham stimulation (7.93 vs. 9.36, p = 0.04). Further, post hoc analysis did not show a significant difference of cue craving between real and sham TMS in healthy controls, while the post hoc results of MA group showed that real TMS induced significantly cue craving than sham TMS (17.86 ± 1.46 vs. 24.85 ± 1.57, p = 0.001). Mean ± SEM; *p < 0.05, **p < 0.01.