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

Abstract

BackgroundChronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modulate cortico-limbic activity resulting in reduction of drug craving.AimsIn 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).MethodsTen 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.ResultsThe two-way ANOVA for repeated measures did not show a significant 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 significant 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.ConclusionBilateral rTMS of PFC at 10 Hz did not show a significant 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 confirm these encouraging but preliminary findings, in order to consolidate rTMS as a valid tool to treat cocaine addiction.

A review of brain stimulation methods to treat substance use disorders

“…Four studies investigated the effects of rTMS on craving for cocaine in dependent adult participants. The number of treatment sessions ranged from 1 to 12, with a frequency range between 5 and 20 Hz.…”

“…The number of treatment sessions ranged from 1 to 12, with a frequency range between 5 and 20 Hz. Three of these studies demonstrated positive results, with a significant reduction in craving for cocaine, with the exception of Bolloni et al who found no significant change in craving compared to sham, although long‐term reduction in consumption was significant when considering time as a factor.…”

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

“…In support of this idea preexisting hyperexcitability of prefrontal and ventral striatum neurons in Tmod2 mutants could actively resist the cocaine-induced depression of these regions, thereby masking the maladaptive behavioral effects of cocaine 104,105 . Interestingly, high frequency (5-20 hz) transcranial magnetic stimulation that increases cortical excitability has been shown to be an effective treatment for cocaine craving [106][107][108] , indicating that cortical excitability in naive Tmod2 KO could interfere and prevent cocaine-induced addiction behavior. Basal and cocaine-induced changes in synaptic properties of accumbens neurons are also distinct from their WT counterparts and support behavioral results.…”

Rewiring the Addicted Brain: Circuits-Based Treatment for Addiction

“…Multiple sessions of high-frequency rTMS of the left DLPFC were reported to reduce spontaneous craving for cocaine and increased the abstinence rates, as assessed by the number of cocainefree drug tests (Terraneo et al 2016). Further pilot clinical studies report that rTMS of the left DLPFC is effective in reducing craving and intake (Politi et al 2008;Bolloni et al 2016;Rapinesi et al 2016). As mentioned earlier, the mechanisms by which rTMS of DLPFC is potentially useful for reducing symptoms related to cocaine addiction are linked to the modulatory effects on neurotransmitter systems (Volkow et al 2004;Diana et al 2017).…”