Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study

Background: Chronic cocaine consumption is associated with a decrease in mesolim- bic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modu- late cortico-limbic activity resulting in reduction of drug craving. Aims: In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods: Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve repetitive TMS (rTMS) sessions were administered three times a week for 4 weeks at 100% of motor threshold, over bilateral PFC. Cocaine intake (ng/mg) was assessed by hair analysis at baseline (before treatment, T0), after 1 month (end of treatment, T1), 3 (T2), and 6 (T3) months later. All subjects received psychological support weekly. Results: The two-way ANOVA for repeated measures did not show a signi cant effect of the interaction between time and treatment (F4,32 = 0.35; p = 0.87). Despite that result indicated no difference in the effect of the two conditions (active vs. sham) along time, a decreasing trend in cocaine consumption in active TMS group (F3,23 = 3.42; p = 0.04) vs. sham (F3,15 = 1.88; p = 0.20) was observed when we performed exploratory analysis with time as factor. Indeed, Post hoc comparisons showed a signi cant reduction in the amount of cocaine detected from the onset to 3 months later (T0–T2; p = 0.02) and to the end of treatment (T0–T3; p = 0.01) in addicts from the active group. Conclusion: Bilateral rTMS of PFC at 10 Hz did not show a signi cant effect on cocaine intake compared to sham. However, a long-term reduction on cocaine intake in active TMS-treated patients was observed when we considered the time as factor. Further studies are required to con rm these encouraging but preliminary ndings, in order to consolidate rTMS as a valid tool to treat cocaine addiction

Transcranial magnetic stimulation for the treatment of cocaine addiction: evidence to date

Corinna Bolloni, Paola Badas, Giorgio Corona, Marco Diana Laboratory of Cognitive Neuroscience, G Minardi Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy Abstract: There is a common consensus in considering substance-use disorders (SUDs) a devastating chronic illness with social and psychological impact. Despite significant progress in understanding the neurobiology of SUDs, therapeutic advances have proceeded at a slower pace, in particular for cocaine-use disorder (CUD). Transcranial magnetic stimulation (TMS) is gaining support as a safe and cost-effective tool in the treatment of SUDs. In this review, we consider human studies that have investigated the efficacy of TMS in achieving therapeutic benefits in treating CUD. All studies conducted to date that have evaluated the therapeutic effect of TMS in CUD are included. We focus on the protocol of stimulation applied, emphasizing the neurophysiological effects of coils employed related to outcomes. Moreover, we examine the subjective and objective measurements used to assess the therapeutic effects along the timeline considered. The revision of scientific literatures underscores the therapeutic potential of TMS in treating CUD. However, the variability in stimulation protocols applied and the lack of methodological control do not allow us to draw firm conclusions, and further studies are warranted to examine the interaction between TMS patterns of stimulation relative to clinical outcomes in depth. Keywords: TMS, cocaine-use disorder, PfCx, craving, intake, dopamin

D-TMS IN COCAINE ADDICTION: preliminary findings

Cocaine-related disorders are currently among the most devastating mental disease as they leads to profound disturbances in an individual\u2019s behaviour resulting in tremendous economic, social, and moral costs. Imaging studies in human have shown a reduction of dopamine (DA) receptors accompanied by a lesser release of endogenous DA in the ventral striatum (AVT) of cocaine subjects thereby resulting in a \u2018dopamine-impoverished\u2019 brain[1-2]. This perturbations lead to neuroadpatations in several other circuits which are related to motivation, inhibitory control, and memory which finally determ compulsive-impulsive self drug administration[3]. The lasting reduction in physiological activity of the DA system leads to the idea that an increment on its activity, to restore pre-drug levels, may yield significant clinical improvements[2]. There is a substantial need for therapeutic tools in addictive states and TMS appears to be a promising \u2018non-pharmacologic\u2019 candidate, since it can modulate the DA system and the function of related areas[4]. It has been just reported[5] that rTMS over the left dorso-lateral prefrontal cortices (DLPfcx) temporarily reduces the craving for cocaine in cocaine addicts but there are no studies which have investigated the TMS effects in the cocaine intake. Considering that we applied bilateral deep-rTMS to the DLPfcx of cocaine abusers, in order (1) to evaluate the short/long term therapeutic effects of TMS in cocaine intake trough hair analysis during the time line (T0,T1,T2,T3.. ), (2) to identify optimal parameters of stimulation (1HZ/10HZ), (3) to highlight possible correlation between cocaine intake and clinical parameters. 20 cocaine abusers have been recruited selected on the DSM-IV criteria and randomly assigned to real rTMS group (100% of motor threshold, 10 HZ/1 HZ, 5 second per train, 20 trains, 15 seconds of inter-stimulus) or to sham stimulation one. In order to investigate the effect of TMS on cocaine dependence we assessed the cocaine intake trough hair analysis before (T0) and after treatment (T1) and every 3 months for the follow-up data. The interim analysis shows that all subjects have reduced the intake of cocaine regardless of the frequency (10 Hz or sham condition) of the stimulation protocol applied. Six months after the treatment (T2) all treated subjects show a reduction in cocaine intake with no distinction among groups (real vs sham). More cases are needed in 1 Hz and sham conditions to \u201cbalance\u201d the groups. The follow-up data, however, shows a strong persistence of the effect in the real group, and decidedly weaker maintenance in sham. We hypothesize an initial placebo/sham effect which disappears over time in the sham patients group. More cases are needed in 1 hz and sham condition to balance the groups. Nevertheless these preliminary data encourage further investigation to evaluate the potential effects of dTMS in the treatment of cocaine abusers and in the prevention of relapses. References 1 Volkow et al., 2010 Bioessays 32(9):748-755 2 Diana, 2011 Front Psychi 2:64 3 Volkow et al., 2004 Neurophar 47:3-13 4 Feil et al., 2010 Neurosci&Biobe 35:248-275 5 Politi et al., 2008 Am J on Add, Vol.17(4): 345-34

Repetitive transcranial magnetic stimulation: Re-wiring the alcoholic human brain

Alcohol use disorders (AUDs) are one of the leading causes of mortality and morbidity worldwide. In spite of significant advances in understanding the neural underpinnings of AUDs, therapeutic options remain limited. Recent studies have highlighted the potential of repetitive transcranial magnetic stimulation (rTMS) as an innovative, safe, and cost-effective treatment for AUDs. Here, we summarize the fundamental principles of rTMS and its putative mechanisms of action via neurocircuitries related to alcohol addiction. We will also discuss advantages and limitations of rTMS, and argue that Hebbian plasticity and connectivity changes, as well as state-dependency, play a role in shaping some of the longterm effects of rTMS. Visual imaging studies will be linked to recent clinical pilot studies describing the effect of rTMS on alcohol craving and intake, pinpointing new advances, and highlighting conceptual gaps to be filled by future controlled studies. (C) 2018 Elsevier Inc. All rights reserved

Rehabilitating the addicted brain with transcranial magnetic stimulation

Substance use disorders (SUDs) are one of the leading causes of morbidity and mortality worldwide. In spite of considerable advances in understanding the neural underpinnings of SUDs, therapeutic options remain limited. Recent studies have highlighted the potential of transcranial magnetic stimulation (TMS) as an innovative, safe and cost-effective treatment for some SUDs. Repetitive TMS (rTMS) influences neural activity in the short and long term by mechanisms involving neuroplasticity both locally, under the stimulating coil, and at the network level, throughout the brain. The long-term neurophysiological changes induced by rTMS have the potential to affect behaviours relating to drug craving, intake and relapse. Here, we review TMS mechanisms and evidence that rTMS is opening new avenues in addiction treatments