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

ABSTRACT: 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.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.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.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.

SUBMITTER: Li X

PROVIDER: S-EPMC4196687 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Li Xingbao X Malcolm Robert J RJ Huebner Kristina K Hanlon Colleen A CA Taylor Joseph J JJ Brady Kathleen T KT George Mark S MS See Ronald E RE

Drug and alcohol dependence 20130826 2

<h4>Background</h4>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.<h4>Methods</h4>In this single-blind, sha ...[more]

PMID: 24028801

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Project description:BackgroundCocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD.MethodsWe conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments.FindingsWe randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9-10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p<0.03) after treatment at T1, corresponding to the end of rTMS treatment. Furthermore, in the rTMS and sham groups, self-reported days of cocaine use decreased significantly (p<0.03). Finally, psychometric impulsivity parameters improved in rTMS-treated patients, while depression scales improved in both groups.ConclusionsIn CUD, rTMS could be a useful tool for lowering cocaine craving and consumption.Trial registrationThe study number on clinicalTrials.gov is NCT03607591.

Project description:BackgroundMethamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity.Materials and methodsIn this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content.ResultsThe expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Discussion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity.DiscussionOur study showed BDNF-positive cells as well as GSH amount, displayed significant declines in DLPFC of MA user. MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. However, further investigations are needed to throw light on the cellular and molecular mechanisms that act in the various regions of the addicted brain, especially in DLPFC.

Dataset Information

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

Publications

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

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