Sleep disruptions are prevalent complaints in cocaine use disorder (CUD) subjects, either during consumption or withdrawal. Repetitive transcranial magnetic stimulation (rTMS) seem to be a promissing strategy in the treatment of chronic cocaine users.

The aim of this study will be to assess the variation on self-perceived sleep quality and drug use variables in individuals with CUD undergoing a rTMS protocol over the left dorsolateral prefrontal cortex (DLPFC).

Cocaine use disorder (CUD) is a chronic relapsing brain disorder characterized by a problematic pattern of cocaine consumption leading to a clinically significant impairment. A core element of this disease is the increased vulnerability to relapse during the first weeks of abstinence. Commonly withdrawal symptoms as sleep disturbances, negative affect or craving, may contributes critically to relapses. Especially, sleep disruptions are frequently referred by CUD individuals during either use or abstinence. Moreover, polysomnographic (PSG) data demonstrate a worsening sleep during the first weeks of abstinence in chronic cocaine users, with diminishing rapid eye movement sleep (REM) time, reduction of total sleep time, increasing sleep latency, and chronically decreased slow-wave sleep (SWS) time. Such sleep anomalies appear to be durable and relate to the severity of withdrawal symptoms and clinical outcomes in the treatment of CUD. However, causality between sleep disturbances and CUD has not been clearly established yet. Interestingly, sleep deprivation and addictive substances have comparable neurobiological effects on several neurotransmitter pathways, particularly in the dopaminergic system. Therefore, the implementation of strategies to rewire the altered brain circuits might induce clinically significant improvements of addictive symptoms and the regulation of sleep patterns in CUD patients.

Recently, transcranial magnetic stimulation (TMS), an innovative and safe brain stimulation procedure, which induce neural electrical activity through the application of magnetic pulses over the scalp and with enduring effects on mood, has been applied as a promising therapeutic approach in addictive disorders. In fact, clinical pilot studies on CUD are giving preliminary support to the potential role of rTMS in decreasing cocaine craving and use. PSG studies in healthy volunteers have shown rTMS-induced changes in sleep architecture that are opposites to those found in CUD subjects, as a prolongation of REM latency or a marked increase in slow-wave sleep. The promising therapeutic effect of TMS on insomnia, restless legs syndrome and on sleep disturbances associated to epilepsy, depression and post-traumatic stress disorder has also been suggested. Further, rTMS application over DLPFC have revealed positives outcomes in patients with chronic primary insomnia, by reducing sleep latency, increasing the total sleep time and REM latency.

These findings suggest that rTMS might impact brain circuitry, modulating relevant functions as sleep architecture and potentially affecting addictive related symptoms as craving or negative affect.

The hypothesis of the present study is that rTMS treatment intervention might have a beneficial effect on sleep disturbances reported by CUD patients during the abstinence/withdrawal period. The investigators hypothesized also the positive outcome on accompanied cocaine withdrawal symptoms (as craving or mood) of rTMS.

Hence, the aims of the present study are:

1. to verify whether rTMS of the left DLPFC in CUD patients produces modifications on the subjective sleep quality patterns and drug use variables.
2. to further strengthen the results of previous CUD-TMS research, the investigators will test whether rTMS of the left DLPFC in CUD patients is safe and reduces cocaine use.

Procedures:

Patients with CUD will be evaluated for sleep disturbances, craving, depression, anxiety and other clinical symptoms by completing the following scales: Pittsburgh Sleep Quality Index (PSQI), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), Alcohol Use Disorders Identification Test (AUDIT) and Symptoms checklist 90 - Revised (SCL-90-R). Participants could be undergo a battery of cognitive tests such as Wisconsin Card Sorting Test (WCST), Stop Signal Task (SST), Iowa Gambling Task (IGT), Stroop task or Delay Discounting Task (DDT). The pattern of drug use will be also monitored by recording drug use variables. The measures will be assessed before the rTMS treatment (baseline), and after 5 (Day 5), 30 (Day 30), 60 (Day 60) and 90 (Day 90) days during the treatment.

Inclusion Criteria:

- Current diagnosis of CUD according to DSM-5;

Exclusion Criteria:

• Pregnancy or breastfeeding;
• Current DSM-5 diagnosis for Schizophrenia Spectrum and Other Psychotic Disorders, Major Depressive Disorder or Bipolar and Related Disorders;
• Current DSM-5 diagnosis for Alcohol and Substance use disorders (except Tobacco use disorders);
• Current DSM-5 diagnosis for Personality disorders;
• Current DSM-5 diagnosis for Primary Sleep-Wake Disorders;
• Prior history of un unstable medical illness, substantial neurological illness, any contraindication for rTMS (including implanted metal and devices in the body, and history of epilepsy);

Participants recruited after referral to specialty outpatient clinic Center for Addiction and meeting diagnostic criteria for Cocaine Use Disorder according to the Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM 5), as assessed by an SUDs expert clinical psychiatrist.