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The involvement of the dopamine system in modulating time perception has been widely reported. Clinical conditions (e.g., Parkinson's disease, addictions) that alter dopaminergic signaling have been shown to affect motor timing and perceived duration. The present study aimed at investigating whether the effects of chronic stimulant use on temporal processing are time-interval dependent. All participants performed two different time bisection tasks (480/1920 ms and 1200/2640 ms) in which we analysed the proportion of long responses for each stimulus duration as well as an index of perceived duration and one of sensitivity. Regarding the proportion of long responses, we found no differences between groups in either time bisection task but patients had more variable results than controls did in both tasks. This study provides new insight into temporal processing in stimulant-dependent patients. Regardless of the time interval tested, the results showed comparable temporal ability in patients and controls, but higher temporal variability in patients. This finding is consistent with impairment of frontally-mediated cognitive functions involved in time perception rather than impairment in time processing per se.

In recent years, hair has become an alternative biological specimen for drug testing in the fields of forensic and clinical toxicology. The advantages of hair testing include larger detection windows (months/years), depending on the length of the hair shaft, compared to those of urine/blood (hours to 2-4 days for most drugs). Segmental hair analysis can disclose a month-to-month (considering 1 cm segment cuts) information of drug exposure (single or repeated) and potentially identify patterns of drug use/administration. Repetitive transcranial magnetic stimulation (rTMS) was recently proposed as a valid tool for therapeutic purposes in addictions, including cocaine use disorder (CocUD). Here, we proposed hair testing analyses of classic drugs of abuse in a clinical setting to monitor the clinical changes in treatment-seeker CocUD patients undergoing protocol treatments with rTMS stimulating the left dorsolateral prefrontal cortex (l-DLPFC). We collected hair samples from nine CocUD patients at different stages from the beginning of treatments. Hair sample analyses revealed significant changes in the patterns of cocaine use, according to the negativity of urine screening tests and the clinical reductions of craving. These data, albeit preliminary, suggest that hair testing analysis of classic drugs of abuse could be extended to clinical settings to monitor the clinical efficacy of innovative therapeutic interventions, such as rTMS.

Background: Adult attention-deficit/hyperactivity disorder (ADHD) is associated with high comorbidity with other psychiatric diseases, including cocaine use disorder (CocUD). Given the common fronto-striatal dysfunction, ADHD patients often use cocaine as self-medication for ameliorating symptoms by increasing striatal dopamine release. Yet, comorbidity with ADHD is related to poor treatment outcomes. CocUD has been treated with transcranial magnetic stimulation (TMS), but no studies investigated the outcomes in patients comorbid with ADHD. Methods: Twenty-two ADHD/CocUD and 208 CocUD-only participants received a high-frequency (15 Hz) rTMS treatment stimulating the left-DLPFC. We investigated whether both groups of patients shared similar demographic and clinical characteristics at baseline. Then, we monitored the effect of treatment testing for potential differences between groups. Results: At baseline demographic, toxicology and clinical features were not different between the two groups except for global severity index (GSI from SCL-90): patients of ADHD/CocUD group reported higher general symptomatology compared to the CocUD-only group. Concerning the effect of treatment, both groups significantly improved over time regarding cocaine use, craving, and other negative affect symptoms. No differences were observed between groups. Conclusions: To our knowledge, this is the first study comparing the demographic characterization and rTMS clinical improvements of patients with a dual diagnosis of ADHD and CocUD against CocUD-only patients. Cocaine use and common self-reported withdrawal/abstinence symptoms appear to benefit from rTMS treatment with no differences between groups. Future studies are needed to further investigate these preliminary results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cardullo, Gómez Pérez, Cuppone, Sarlo, Cellini, Terraneo, Gallimberti and Madeo.)

Background: Sleep disturbance is a prominent and common complaint in people with cocaine use disorder (CUD), either during intake or withdrawal. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a treatment for CUD. Thus, we evaluated the relationship between self-perceived sleep quality and cocaine use pattern variables in outpatients with CUD undergoing an rTMS protocol targeted at the left dorsolateral prefrontal cortex., Methods: This is a retrospective observational study including 87 patients diagnosed with CUD according to the DSM-5 criteria. Scores in Pittsburgh Sleep Quality Index (PSQI), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), and Symptoms checklist 90-Revised (outcome used: Global Severity Index, GSI) were recorded at baseline, and after 5, 30, 60, and 90 days of rTMS treatment. Cocaine use was assessed by self-report and regular urine screens., Results: Sleep disturbances (PSQI scores > 5) were common in patients at baseline (mean ± SD; PSQI score baseline: 9.24 ± 3.89; PSQI > 5 in 88.5% of patients). PSQI scores significantly improved after rTMS treatment (PSQI score Day 90: 6.12 ± 3.32). Significant and consistent improvements were also seen in craving and in negative-affect symptoms compared to baseline. Considering the lack of a control group, in order to help the conceptualization of the outcomes, we compared the results to a wait-list group (n = 10). No significant improvements were observed in the wait-list group in any of the outcome measures., Conclusions: The present findings support the therapeutic role of rTMS interventions for reducing cocaine use and accompanying symptoms such as sleep disturbance and negative-affect symptoms., Trial Registration: ClinicalTrials.gov.NCT03733821.

Background: Cocaine is a psychostimulant drug used as performance enhancer throughout history. The prolonged use of cocaine is associated with addiction and a broad range of cognitive deficits. Currently, there are no medications proven to be effective for cocaine-use disorder (CocUD). Previous preliminary clinical work suggests some benefit from repetitive transcranial magnetic stimulation (rTMS) stimulating the prefrontal cortex (PFC), involved in inhibitory cognitive control, decision-making and attention. All published studies to date have been limited by small sample sizes and short follow-up times. Methods: This is a retrospective observational study of 284 outpatients (of whom 268 were men) meeting DSM-5 criteria for CocUD. At treatment entry, most were using cocaine every day or several times per week. All patients underwent 3 months of rTMS and were followed for up to 2 years, 8 months. Self-report, reports by family or significant others and regular urine screens were used to assess drug use. Results: Median time to the first lapse (resumption of cocaine use) since the beginning of treatment was 91 days. For most patients, TMS was re-administered weekly, then monthly, throughout follow-up. The decrease in frequency of rTMS sessions was not accompanied by an increase in lapses to cocaine use. Mean frequency of cocaine use was <1·0 day/month (median 0), while serious rTMS-related adverse events were infrequent, consistent with published reports from smaller studies. Conclusions: This is the first follow-up study to show that rTMS treatment is accompanied by long-lasting reductions in cocaine use in a large cohort., (Copyright © 2020 Madeo, Terraneo, Cardullo, Gómez Pérez, Cellini, Sarlo, Bonci and Gallimberti.)

(1) Background: Pathological gambling behaviors may coexist with cocaine use disorder (CUD), underlying common pathogenic mechanisms. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a therapeutic intervention for CUD. In this case series, we evaluated the clinical effects of rTMS protocol stimulating the left dorsolateral prefrontal cortex (DLPFC) on the pattern of gambling and cocaine use. (2) Methods: Gambling severity, craving for cocaine, sleep, and other negative affect symptoms were recorded in seven patients with a diagnosis of gambling disorder (South Oaks Gambling Screen (SOGS) >5), in comorbidity with CUD, using the following scales: Gambling-Symptom Assessment Scale (G-SAS), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), and Symptoms checklist-90 (SCL-90). The measures were assessed before the rTMS treatment and after 5, 30, and 60 days of treatment. Patterns of gambling and cocaine use were assessed by self-report and regular urine screens. (3) Results: Gambling severity at baseline ranged from mild to severe (mean ± Standard Error of the Mean (SEM), G-SAS score baseline: 24.42 ± 2.79). G-SAS scores significantly improved after treatment (G-SAS score Day 60: 2.66 ± 1.08). Compared to baseline, consistent improvements were significantly seen in craving for cocaine and in negative-affect symptoms. (4) Conclusions: The present findings provide unprecedent insights into the potential role of rTMS as a therapeutic intervention for reducing both gambling and cocaine use in patients with a dual diagnosis.

Individual, social and situational factors might play an important role on the experience of anxiety during musical performances. The present research focused on the relationship between self-representations, including musical self, and performance anxiety among a sample of Italian professional and amateur musicians (N = 100; age, M = 23.40, 50% females). We predicted that higher self-discrepancies (actual vs. future self) would be associated with higher performance anxiety in a musical setting (vs. a non musical one), via musical self, and only in professional musicians. The results confirmed our hypothesis. Higher discrepancies between actual and future self-representations were positively associated with higher performance anxiety levels via the musical self only in participants who play instruments at a professional level. Furthermore, musical self influenced performance anxiety levels in a music related setting (i.e., a concert) but not in a non musical one (i.e., an exam)., Competing Interests: The authors have declared that no competing interests exist.