Effect of HF rTMS on Serum BDNF in Cocaine Use Disorder

This study aims to explore the effect of 5-Hz rTMS over the left dorsolateral prefrontal cortex on the BDNF, craving and cognitive function. This study will be longitudinal, with a short-term double-blind placebo-controlled phase consisting of 20 rTMS sessions and a long-term phase, consisting of 2 weekly sessions for 12 weeks. Participants will be clinically assessed pre-treatment (T0), after 20-sessions phase (T1) and after 12-weeks phase (T2) by an interview about psychiatric symptoms. Also, blood will be obtained in the same T0, T1 and T2 to peripheral levels of BDNF determination. Cognitive state will be measured at the same time-points (T0, T1, T2) by paper-pencil and computerized neuropsychological assessment. Researchers will compare active rTMS versus placebo 5 Hz-rTMS on described variables. Additionally, a comparative group (without rTMS intervention) will be included to equivalently measure described variables during periods without cocaine consumption.

Brain derived neurotrophic factor (BDNF) is a widely explored neurotrophin in preclinical models of cocaine addiction with relevant phase and region dependent dynamics along addictive cycle. In humans with cocaine use disorder (CUD), peripheral BDNF have revealed relationship with relevant treatment outcomes as relapse and time of abstinence. In CUD several interventional studies using high frequency repetititve transcranial magnetic stimulation (rTMS) have shown craving reduction, mood improvements and sustained modifications in functional conectivity measued by fMRI. Due to the relevance of BDNF in CUD, and neuroplasticity-related processes derived from rTMS interventions, this study aims to determine changes in peripheral BDNF, craving, cognition in CUD in reponse to rTMS. Aditionally, other outcomes will be considered as depression, anxiety and motivational changes. Procedure: Psychiatric clinical and cognitive assessment, and blood collection will be performed at T0, T1 and T2 time-points. Short-term rTMS phase will consist of two weeks (weekdays) with 2 rTMS or rTMS-placebo sessions (detaills in arms section). Then, two sessions per week along 12 weeks as maintenance therapy will be considered. No rTMS group will attend the same time points and assessment in a controlled facility.