D-TMS IN COCAINE ADDICTION: PRELIMINARY FINDINGS

Cocaine addiction is a phatological state characterized by a marked decrease in the levels of D2 receptors and in the amount of Dopamine (DA) released by DA cells [1]. This perturbations lead to neuroadpatations in several other circuits involved in motivation, inhibitory control, and memory which finally determ compulsive-impulsive drug self-administration [2]. Thus \u2018restoring\u2019 pre-pathology DA activity may yield clinical benefits [3]. There is a substantial need for therapeutic tools in addictive states, and TMS appears to be a promising \u201cnon-pharmacologic\u201d candidate, since it can modulate the DA system and the function of related areas [4] . In the cocaine addict there is a disregulation of the mesolimbic dopaminergic system (AVT, NaC, COF, CCA, CPFvm) which in turn result inhibits [5; 6]. We hypothesize that bilateral TMS application over the Dorsolateral Prefrontal-cortex may \u2018indirectly\u2019 stimulate DA physiological activity by increasing DA level in the human brain [7] thereby producing a reduction in cocaine intake. Considering that TMS parameters are pivotal in the resilience of its neural effects, (2) the project aims at identifying stimulation parameters with higher chance to resemble long term effects. Principles [8; 9] \u2022 Deep Transcranial Magnetic Stimulation (dTMS) \u2022 Depolarization of target neurons \u2022 Excitatory Effects Fr > 5Hz \u2022 Inhibitory Effects Fr 64 1Hz Protocol A double-blind randomized control study \u2022 Subject: - 30 Cocaine Addicts (CA) (DSM-IV); - 2 SG CA (Real 10Hz)/CA (Real 1Hz) - 1 CG CA sham dTMS \u2022 Treatment: - 12 sessions dTMS: 3 sessions/week, for 4 weeks - Parameters (%): Motor Threshold (MT) 110% - Frequency (Hz): 10 Hz or 1Hz randomly assigned - Duration of Stimulation: 8 minutes - Follow Up (FU): 3/6/12 months. Although preliminary, the data show a trend toward a significant reduction in cocaine intake. At the 2FU (six month after treatment) all treated subjects show a reduction in cocaine intake. More cases are needed in the 1 Hz and SHAM group. Nevertheless further investigation is encouraged by this ad interim analysis. [1] Volkow et al., 2010 Bioessays 32(9):748-755 [2] Volkow et al.,2004 Neurophar 47:3-13 [3] Diana, 2 011 Front Psychi 2:64 [4] Feil et al., 2010 Neurosci&Biobe 35:248-275 [5] Melis et al., 2005 Inter Rev Neurob 63:101-154 [6] Koob et al., 2010Neuropsychoph 35 (1):217-38 [7] Strafella et al., 2003 Brain 126:2609-2615 [8] Miniussi et al., 2011 Psychology Press 1-23 [9] Rossi et al., 2009 Clini Neurophysiol 120 (12):2008-3