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:
to verify whether rTMS of the left DLPFC in CUD patients produces modifications on the
subjective sleep quality patterns and drug use variables.
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.