Effect of HF rTMS on Serum BDNF in Cocaine Use Disorder

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.

Inclusion criteria

• Current cocaine use disorder according to the Diagnostic and statistical manual of mental disorders (DSM 5).
• Cocaine crack or powder use for at least 12 months with a frequency of 3 times or more per week, with abstinence periods shorter than 1 year for the last year.
• Primary school completed.

Exclusion criteria

• Personal or first degree family history of any neurological disorder including, but not limited to, organic brain syndrome, epilepsy, brain injuries, multiple sclerosis, conditions that increase intracranial pressure.
• Personal history of brain surgery or traumatic brain injury.
• Comorbilities that could represent a risk of neuroinfection or increased convulsive threshoid.
• Other than alcohol, tobacco or marijuana substance use disorder.
• If the patient does not meet the safety criteria for rTMS.
• Current use of any medication that might provoque seizures or any anticonvulsant drugs.
• Personal history of schizophrenia, mania/hypomania or OCD.
• Personal history of myocardial infarction, angina, congestive heart failure, cerebrovascular events, transient ischemic attack or any other heart condition currently undergoing medical treatment.
• Personal history of seizures or detection of paroxysmal EEG activity.