A clinical research project is currently underway at Careggi University Hospital in Florence to evaluate the effectiveness of a noninvasive neuromodulation technique in treating cocaine use disorder. The intervention is based on repetitive transcranial magnetic stimulation (rTMS), a method that uses magnetic fields to specifically modulate the activity of specific brain areas, without the need for surgery or medication.
The primary objective of the trial is to verify whether this procedure can attenuate the compulsive impulse that drives addicts to repeatedly seek and take the substance—a phenomenon known clinically as craving, or intense and persistent desire—thus helping to reduce the risk of relapse and improve patients’ quality of life.
The study design has undergone rigorous scientific validation: a preliminary phase, conducted using a controlled methodology, was recently published in the journal Clinical Neurophysiology (not Neurophysiologie Clinique, likely a confusion in the original version; the corrected journal is the most widely read in the international literature on the topic), confirming the feasibility and safety of the proposed protocol.
Why is this research significant?
According to the World Health Organization (WHO, 2023), approximately 23 million people worldwide use cocaine each year, with a worrying increase in the last five years, especially in Southern Europe. In Italy, data from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA, 2024) indicate that cocaine remains the second most commonly used illegal substance after cannabis, with a 12% increase in treatment requests at Addiction Services (Ser.D) between 2020 and 2024.
Despite the severity of the problem, there are currently no medications specifically approved for cocaine addiction. Available therapeutic strategies—such as cognitive-behavioral psychotherapy, self-help groups (e.g., Cocaine Anonymous), and psychosocial support interventions—show benefits, but 12-month relapse rates exceed 60% (Source: The Lancet Psychiatry, 2022). This gap has prompted the scientific community to explore complementary neurobiological approaches, including noninvasive neuromodulation.
In particular, neuroimaging studies have shown that cocaine craving is associated with reduced activation of the dorsolateral prefrontal cortex (DLPFC), a key region for executive functions—such as impulse inhibition, planning, and decision-making. rTMS, applied to this area, can increase cortical excitability, partially restoring the neural circuits compromised by addiction. Recent meta-analyses (e.g., JAMA Psychiatry, 2023) report modest but statistically significant effects of rTMS on reducing craving in substance use disorders, with an excellent safety profile.
Study Design at Careggi
The ongoing clinical trial is being conducted jointly by the Departments of Medical Toxicology, Clinical Neurophysiology, and Psychiatry at the Careggi University Hospital, under the scientific direction of Professor Guido Mannaioni, Director of the Toxicology Unit and the School of Specialization in Pharmacology and Clinical Toxicology at the University of Florence.
The trial follows the gold standard of clinical research: it is a randomized, placebo-controlled, double-blind trial, meaning neither the patients nor the researchers involved in the evaluation know whether the device used in a given session is actually delivering magnetic stimulation or is turned off (sham condition). This approach allows us to isolate the specific effect of rTMS from the placebo effect, which is particularly relevant in neuropsychiatry, where expectations can significantly influence subjective outcomes.
The protocol includes:
Baseline assessment: clinical, psychiatric, and toxicological screening (via urine and hair tests to detect recent and chronic use);
Treatment phase: 20 rTMS sessions, five times a week for four weeks, with a stimulation frequency of 10 Hz on the left DLPFC, according to parameters optimized in previous studies;
Follow-up: 12-week post-intervention monitoring, with weekly assessments of craving (using validated scales such as the Cocaine Craving Questionnaire – Now version), substance use, and psychosocial functioning.
Men and women aged 18 to 65 with a confirmed diagnosis of active cocaine use disorder (according to DSM-IV criteria) are eligible to participate.
