Cocaine Use Disorder Patients Research Articles

Predictors of abstinence maintenance after cocaine inpatient detoxification: A prospective study.

Cocaine is a highly addictive substance, and with no approved medication for cocaine use disorder (CUD), leading to a heavy burden. Despite validated psychosocial treatments, relapse rates after detoxification are very high in CUD. Few consistent factors can predict abstinence after detoxification. Our study, therefore, aimed at identifying factors predicting abstinence among CUD patients after inpatient detoxification. Eighty-one CUD inpatients were included during detoxification and characterized for clinical and sociodemographic data at baseline and at a follow-up of 3 months after discharge, including a standard measure of their abstinence duration from cocaine. We performed Cox univariate analyzes to determine the factors associated with abstinence maintenance, followed by a multivariate Cox regression to identify independent predictors. Abstinence maintenance was shorter in patients injecting cocaine (hazard ratio [HR] = 5.16, 95% confidence interval [CI]: 2.01-13.27, p < .001) and using cocaine heavily in the month before inclusion (HR = 1.03, 95% CI: 1.00-1.06, p = .046). Conversely, abstinence maintenance was longer in patients with longer inpatient detoxification stays (HR = 0.96, 95% CI: 0.94-0.99, p = .015) and prescribed with selective serotonin reuptake inhibitors (SSRIs) (HR = 0.30, 95% CI: 0.16-0.56, p < .001). Patients with severe CUD may require longer inpatient stays to achieve abstinence. Regarding SSRI prescription, more specific studies are needed to provide stronger recommendations about their use in clinical practice. Our findings suggest several modifiable factors to improve inpatient treatment response in CUD. As there are no specific recommendations about the optimal duration of inpatient stay, our results could pave the way for evidence-based guidelines.

Disrupted dynamic brain functional connectivity in male cocaine use disorder: Hyperconnectivity, strongly-connected state tendency, and links to impulsivity and borderline traits

Cocaine use is a major public health problem with serious negative consequences at both the individual and societal levels. Cocaine use disorder (CUD) is associated with cognitive and emotional impairments, often manifesting as alterations in brain functional connectivity (FC). This study employed resting-state functional magnetic resonance imaging (rs-fMRI) to examine dynamic FC in 38 male participants with CUD and 31 matched healthy controls. Using group spatial independent component analysis (group ICA) combined with sliding window approach, we identified two recurring distinct connectivity states: the strongly-connected state (state 1) and weakly-connected state (state 2). CUD patients exhibited significant increased mean dwell and fraction time in state 1, and increased transitions from state 2 to state 1, demonstrated significant strongly-connected state tendency. Our analysis revealed abnormal FC patterns that are state-dependent and state-shared in CUD patients. This study observed hyperconnectivity within the default mode network (DMN) and between DMN and other networks, which varied depending on the state. Furthermore, after adjustment for multiple comparisons, we found significant correlations between these altered dynamic FCs and clinical measures of impulsivity and borderline personality disorder. The disrupted FC and repetitive effects of precuneus and angular gyrus across correlations suggested that they might be the important hub of neural circuits related behaviorally and mentally in CUD. In summary, our study highlighted the potential of these disrupted FC as neuroimaging biomarkers and therapeutic targets, and provided new insights into the understanding of the neurophysiologic mechanisms of CUD.

Non-local diffusion-based biomarkers in patients with cocaine use disorder

Cocaine use disorder (CUD) is widely known to result in neurological reconfiguration which can be observed via local diffusivity characteristics of the brain. These changes can be highly correlated while simultaneously variable across patients with different comorbidities or histories of substance use. This implies that more complex neuroimage analysis tools may be necessary to better detect specific biomarkers that vary across these dimensions. We investigated white and gray matter integrity using voxel-based diktiometry (VBD) on whole brain diffusion tensor images (DTI) across a database of CUD patients and healthy controls using a purely data-driven approach. These VBD maps reveal significant cortical and subcortical differences that are indicative of these neural modifications including the insula, cerebellum, ventricles, thalamo-cortical radiations, and corpus callosum bundles. In order to disambiguate these results and investigate the heterogeneity of CUD, the VBD maps have been decomposed into five decorrelated biomarkers: one in the region surrounding the left insula, one implicating the corpus callosum, two concentrated in the left cerebellum, and the last concerning a proximal region of the interhemispheric fissure which serve as potential biomarkers playing a role in CUD. These decorrelated biomarkers have themselves been correlated with consumption patterns and psychiatric and borderline personality disorder scores on the CUD patient group. This preliminary approach to using machine learning techniques to both detect and disambiguate complex non-linear patterns shows promise for better understanding complex and heterogeneous disorders such as CUD.

The Mexican dataset of a repetitive transcranial magnetic stimulation clinical trial on cocaine use disorder patients: SUDMEX TMS

Cocaine use disorder (CUD) is a global health problem with severe consequences, leading to behavioral, cognitive, and neurobiological disturbances. While consensus on treatments is still ongoing, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach for medication-resistant disorders, including substance use disorders. In this context, here we present the SUDMEX-TMS, a Mexican dataset from an rTMS clinical trial involving CUD patients. This longitudinal dataset comprises 54 CUD patients (including 8 females) with data collected at five time points: baseline (T0), two weeks (T1), three months (T2), six months (T3) follow-up, and twelve months (T4) follow-up. The clinical rTMS treatment followed a double-blinded randomized clinical trial design (n = 24 sham/30 active) for 2 weeks, followed by an open-label phase. The dataset includes demographic, clinical, and cognitive measures, as well as magnetic resonance imaging (MRI) data collected at all time points, encompassing structural (T1-weighted), functional (resting-state fMRI), and multishell diffusion-weighted (DWI-HARDI) sequences. This dataset offers the opportunity to investigate the impact of rTMS on CUD participants, considering clinical, cognitive, and multimodal MRI metrics in a longitudinal framework.

Time perception in stimulant-dependent participants undergoing repetitive transcranial magnetic stimulation

BackgroundThe dopaminergic (DA) system is an important neural system for the modulation of time perception and the timing of motor actions. Dysregulation of the DA system is related to chronic use of stimulant drugs, which lead, among others, to executive dysfunctions. Little is known instead about the potential deficiencies in temporal processing of stimulant-dependent individuals. The present study aimed to investigate temporal processing using a time bisection task with different temporal intervals in chronic cocaine users undergoing repetitive transcranial magnetic stimulation (rTMS). MethodStudy 1: A time bisection task with short temporal intervals range (480/1920 ms) was administered to 18 cocaine use disorder (CocUD) patients and 20 healthy control before and after the intensive phase of rTMS treatment (5 days apart). Study 2: 22 CocUD participants and 23 control participants completed two temporal tasks (time bisection and time reproduction) with long temporal intervals range (1200/2640 ms) at baseline and immediately after the intensive phase of rTMS treatment. ResultsStudy 1: A shift in the psychometric function consistent with temporal overestimation in CocUD patients compared to controls was observed. However, no temporal impairment in CocUD patients at test session was found. Study 2: The analysis of temporal variability indices showed a significant difference between groups at baseline but not at Day 5 due to a significant difference between time points only in the CocUD group. ConclusionsThis study report a temporal overestimation in CocUD patients and a temporal variability reduction after an rTMS protocol in CocUD patients.

Mismatch of Biological and Social Time in Cocaine-Addicted Men

Introduction: Chronotype describes a person’s preferential activity pattern during a 24-hour period, which may not be in line with their social lifestyle. A mismatch between biological and social time is known as “social jetlag,” which has negative effects on wellbeing. Cocaine influences a person’s activity levels, but very little is known about possible changes in chronotype of patients with cocaine use disorder (CUD). Here, we aimed to shed light on self-reported changes in chronotype in patients with CUD and the clinical implications. Methods: A total of 90 men from the local community were recruited; about half of the sample met the criteria for CUD, while the other half were healthy without a personal history of substance use disorder. Participants completed the Munich Chronotype Questionnaire along with questionnaires about mental health, daily fatigue, and drug/alcohol use. Results: Half of the CUD patients fell into the category of late chronotype – a significantly larger proportion than their healthy peers. Late “night owls” tended to have started using cocaine at an earlier age than other chronotypes; a finding that was not observed with tobacco, cannabis, or alcohol. Drug use severity in CUD patients did not differ across chronotypes. CUD patients (52%) did not have a preferred time of day to use cocaine. The mismatch between social and biological time was significantly greater in CUD patients and unrelated to drug use or mental health status. Conclusion: CUD appears to be associated with disruptions in chronotype which are, contrary to a widely held view, not reflected by using patterns or addiction severity.

Lower cortical thickness and increased brain aging in adults with cocaine use disorder.

Cocaine use disorder (CUD) is a global health issue with severe behavioral and cognitive sequelae. While previous evidence suggests a variety of structural and age-related brain changes in CUD, the impact on both, cortical thickness and brain age measures remains unclear. Derived from a publicly available data set (SUDMEX_CONN), 74 CUD patients and 62 matched healthy controls underwent brain MRI and behavioral-clinical assessment. We determined cortical thickness by surface-based morphometry using CAT12 and Brain Age Gap Estimate (BrainAGE) via relevance vector regression. Associations between structural brain changes and behavioral-clinical variables of patients with CUD were investigated by correlation analyses. We found significantly lower cortical thickness in bilateral prefrontal cortices, posterior cingulate cortices, and the temporoparietal junction and significantly increased BrainAGE in patients with CUD [mean (SD) = 1.97 (±3.53)] compared to healthy controls (p < 0.001, Cohen's d = 0.58). Increased BrainAGE was associated with longer cocaine abuse duration. Results demonstrate structural brain abnormalities in CUD, particularly lower cortical thickness in association cortices and dose-dependent, increased brain age.

Plasma Lysophosphatidic Acid Concentrations in Sex Differences and Psychiatric Comorbidity in Patients with Cocaine Use Disorder.

We have recently reported sex differences in the plasma concentrations of lysophosphatidic acid (LPA) and alterations in LPA species in patients with alcohol and cocaine use disorders. Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in anxiogenic responses and drug addiction. To further explore the potential role of the LPA signaling system in sex differences and psychiatric comorbidity in cocaine use disorder (CUD), we conducted a cross-sectional study with 88 patients diagnosed with CUD in outpatient treatment and 60 healthy controls. Plasma concentrations of total LPA and LPA species (16:0, 18:0, 18:1, 18:2 and 20:4) were quantified and correlated with cortisol and tryptophan metabolites [tryptophan (TRP), serotonin (5-HT), kynurenine (KYN), quinolinic acid (QUIN) and kynurenic acid (KYNA)]. We found sexual dimorphism for the total LPA and most LPA species in the control and CUD groups. The total LPA and LPA species were not altered in CUD patients compared to the controls. There was a significant correlation between 18:2 LPA and age at CUD diagnosis (years) in the total sample, but total LPA, 16:0 LPA and 18:2 LPA correlated with age at onset of CUD in male patients. Women with CUD had more comorbid anxiety and eating disorders, whereas men had more cannabis use disorders. Total LPA, 18:0 LPA and 20:4 LPA were significantly decreased in CUD patients with anxiety disorders. Both 20:4 LPA and total LPA were significantly higher in women without anxiety disorders compared to men with and without anxiety disorders. Total LPA and 16:0 LPA were significantly decreased in CUD patients with childhood ADHD. Both 18:1 LPA and 20:4 LPA were significantly augmented in CUD patients with personality disorders. KYNA significantly correlated with total LPA, 16:0 LPA and 18:2 LPA species, while TRP correlated with the 18:1 LPA species. Our results demonstrate that LPA signaling is affected by sex and psychiatric comorbidity in CUD patients, playing an essential role in mediating their anxiety symptoms.

Structural and functional pathology in cocaine use disorder with polysubstance use: A multimodal fusion approach structural-functional pathology in cocaine use disorder

Cocaine use disorder (CUD) is described as a compulsive urge to seek and consume cocaine despite the inimical consequences. MRI studies from different modalities have shown that CUD patients exhibit structural and/or functional connectivity pathology among several brain regions. Nevertheless, both connectivities are commonly studied and analyzed separately, which may potentially obscure its relationship between them, and with the clinical pathology. Here, we compare structural and functional brain networks in CUD patients and healthy controls (HC) using multimodal fusion. The sample consisted of 63 (8 females) CUD patients and 42 (9 females) healthy controls (HC), recruited as part of the SUDMEX CONN database. For this, we computed a battery of graph-based measures from multi-shell diffusion-weighted imaging and resting state fc-fMRI to quantify local and global connectivity. Then we used multimodal canonical component analysis plus joint independent component analysis (mCCA+jICA) to compare between techniques and evaluate group differences and its association with clinical alteration. Unimodal results showed a striatal decrease in the participation coefficient but applied supervised data fusion revealed other regions with cocaine-related alterations in joint functional communication. When performing multimodal fusion analysis, we observed a higher centrality of the interrelationship and a lower participation coefficient in patients with CUD. In contrast to the unimodal approach, the multimodal fusion method was able to reveal latent information about brain regions involved in impairment due to cocaine abuse. The present results could help in understanding the pathology of CUD to develop better pre-treatment/post-treatment intervention designs.

The impact of childhood maltreatment on telomere length in cocaine use disorder

ABSTRACT Background Several studies suggest that child maltreatment (CM) is a risk factor for a wide range of adverse biological and psychological outcomes, such as cocaine use disorder (CUD). CM and CUD are independently associated with altered telomere length (TL), but the mechanisms that underpin this relationship remain unknown. The aim of this study was to examine TL changes in cocaine-addicted individuals with and without CM. Methods This study comprised 29 cocaine-addicted individuals with a DSM-5 diagnosis of CUD and 29 healthy controls. All subjects completed questionnaires to evaluate the presence of CM (CTQ-SF) and their perceived parental care quality (PBI). Based on the responses, the CUD sample was divided into subgroups, while the control group was selected based on the absence of CM. Blood was collected from all participants, DNA was extracted, and TL was measured using quantitative real-time PCR. Results CUD patients with a history of CM had the shortest TL among subgroups. Further, we observed a linear relationship between “paternal care” levels experienced in childhood and TL. Conclusion These results support the association between telomere shortening with CM and drug addiction and suggest that greater parental care is a protective factor against stressors that affect TL.

Neurobiological Dysfunctional Substrates for the Self-Medication Hypothesis in Adult Individuals with Attention-Deficit Hyperactivity Disorder and Cocaine Use Disorder: A Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Study.

Objectives: Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with attention-deficit hyperactivity disorder with cocaine use disorder (ADHD-CoUD). Materials and Methods: We included 19 ADHD-CoUD patients (84.2% male; age: 32.11 years [7.18]) and 16 CoUD patients (68.7% male; age: 36.63 years [8.12]). All subjects underwent a fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. Results: The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, than CoUD subjects and healthy controls (HCs). Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD patients had a more preserved metabolic connectivity than CoUD patients in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviors (i.e., anterior default mode network [ADMN], executive network [ECN], and anterior salience network [aSAN]). Conclusions: We demonstrated distinct neuropathological substrates underlying substance-use behaviors in ADHD-CoUD and CoUD patients. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD patients might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioral deficits).

Cocaine Destroys Gray Matter Brain Cells and Accelerates Brain Aging.

Introduction: Cocaine use disorder (CUD) is a substance use disorder characterized by a strong desire to obtain, consume, and misuse cocaine. Little is known about how cocaine affects the structure of the brain. In this study, we first investigated the anatomical brain changes in individuals with CUD compared to their matched healthy controls, and then explored whether these anatomical brain abnormalities contribute to considerably accelerated brain aging among this population. Methods: At the first stage, we used anatomical magnetic resonance imaging (MRI) data, voxel-based morphometry (VBM), and deformation-based morphometry techniques to uncover the morphological and macroscopic anatomical brain changes in 74 CUD patients compared to 62 age- and sex-matched healthy controls (HCs) obtained from the SUDMEX CONN dataset, the Mexican MRI dataset of patients with CUD. Then, we computed brain-predicted age difference (i.e., brain-PAD: the brain-predicted age minus the actual age) in CUD and HC groups using a robust brain age estimation framework. Using a multiple regression analysis, we also investigated the regional gray matter (GM) and white matter (WM) changes associated with the brain-PAD. Results: Using a whole-brain VBM analysis, we observed widespread gray matter atrophy in CUD patients located in the temporal lobe, frontal lobe, insula, middle frontal gyrus, superior frontal gyrus, rectal gyrus, and limbic lobe regions compared to the HCs. In contrast, we did not observe any swelling in the GM, changes in the WM, or local brain tissue atrophy or expansion between the CUD and HC groups. Furthermore, we found a significantly higher brain-PAD in CUD patients compared to matched HCs (mean difference = 2.62 years, Cohen's d = 0.54; t-test = 3.16, p = 0.002). The regression analysis showed significant negative changes in GM volume associated with brain-PAD in the CUD group, particularly in the limbic lobe, subcallosal gyrus, cingulate gyrus, and anterior cingulate regions. Discussion: The results of our investigation reveal that chronic cocaine use is linked to significant changes in gray matter, which hasten the process of structural brain aging in individuals who use the drug. These findings offer valuable insights into the impact of cocaine on the composition of the brain.

Oral and fecal microbiota perturbance in cocaine users: Can rTMS-induced cocaine abstinence support eubiosis restoration?

The effects of cocaine on microbiota have been scarcely explored. Here, we investigated the gut (GM) and oral (OM) microbiota composition of cocaine use disorder (CUD) patients and the effects of repetitive transcranial magnetic stimulation (rTMS). 16S rRNA sequencing was used to characterize GM and OM, whereas PICRUST2 assessed functional changes in microbial communities, and gas-chromatography was used to evaluate fecal short and medium chain fatty acids. CUD patients reported a significant decrease in alpha diversity and modification of the abundances of several taxa in both GM and OM. Furthermore, many predicted metabolic pathways were differentially expressed in CUD patients' stool and saliva samples, as well as reduced levels of butyric acid that appear restored to normal amounts after rTMS treatment. In conclusion, CUD patients showed a profound dysbiotic fecal and oral microbiota composition and function and rTMS-induced cocaine abstinence determined the restoration of eubiotic microbiota.

Repurposing ketamine to treat cocaine use disorder: integration of artificial intelligence-based prediction, expert evaluation, clinical corroboration and mechanism of action analyses.

Cocaine use disorder (CUD) is a significant public health issue for which there is no Food and Drug Administration (FDA) approved medication. Drug repurposing looks for new cost-effective uses of approved drugs. This study presents an integrated strategy to identify repurposed FDA-approved drugs for CUD treatment. Our drug repurposing strategy combines artificial intelligence (AI)-based drug prediction, expert panel review, clinical corroboration and mechanisms of action analysis being implemented in the National Drug Abuse Treatment Clinical Trials Network (CTN). Based on AI-based prediction and expert knowledge, ketamine was ranked as the top candidate for clinical corroboration via electronic health record (EHR) evaluation of CUD patient cohorts prescribed ketamine for anesthesia or depression compared with matched controls who received non-ketamine anesthesia or antidepressants/midazolam. Genetic and pathway enrichment analyses were performed to understand ketamine's potential mechanisms of action in the context of CUD. The study utilized TriNetX to access EHRs from more than 90 million patients world-wide. Genetic- and functional-level analyses used DisGeNet, Search Tool for Interactions of Chemicals and Kyoto Encyclopedia of Genes and Genomes databases. A total of 7742 CUD patients who received anesthesia (3871 ketamine-exposed and 3871 anesthetic-controlled) and 7910 CUD patients with depression (3955 ketamine-exposed and 3955 antidepressant-controlled) were identified after propensity score-matching. EHR analysis outcome was a CUD remission diagnosis within 1 year of drug prescription. Patients with CUD prescribed ketamine for anesthesia displayed a significantly higher rate of CUD remission compared with matched individuals prescribed other anesthetics [hazard ratio (HR) = 1.98, 95% confidence interval (CI) = 1.42-2.78]. Similarly, CUD patients prescribed ketamine for depression evidenced a significantly higher CUD remission ratio compared with matched patients prescribed antidepressants or midazolam (HR = 4.39, 95% CI = 2.89-6.68). The mechanism of action analysis revealed that ketamine directly targets multiple CUD-associated genes (BDNF, CNR1, DRD2, GABRA2, GABRB3, GAD1, OPRK1, OPRM1, SLC6A3, SLC6A4) and pathways implicated in neuroactive ligand-receptor interaction, cAMP signaling and cocaine abuse/dependence. Ketamine appears to be a potential repurposed drug for treatment of cocaine use disorder.

Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis.

CUD, like other addictions, is a chronic disease characterized by a high rate of relapse and drop-out (DO) from medical and behavioral treatment programs, which is positively correlated with relapse. Repetitive transcranial Magnetic Stimulation (rTMS) protocols have shown therapeutic potential in addiction in the short term, but only a few studies have explored their long-term efficacy, so far. This study explores the long-term outcome of bilateral intermittent theta-burst stimulation (iTBS) of the prefrontal cortex (PFC) in cocaine use disorder (CUD) and the possible influence of maintenance treatment in improving abstinence and decreasing DO rates. Eighty-nine treatment-seeking CUD patients were exposed to 20 sessions of iTBS. At the end of the treatment 61 (81%) abstinent patients underwent a 12 months follow-up. Among these, 27 patients chose to follow a maintenance treatment (M), whereas 34 patients chose not to adhere to a maintenance treatment (NM). Overall, among patients reaching the 12 months follow-up endpoint, 69.7% were still abstinent and 30.3% relapsed. In NM-patients the DO rate was significantly higher than in M-ones (58.82 vs. 29.63%). The present observations show the long-term therapeutic effect of bilateral PFC iTBS to decrease cocaine consumption. Moreover, they underline the importance to perform a maintenance protocol to consolidate abstinence and decrease DO rates over time.

From a Cycle to a Period: The Potential Role of BDNF as Plasticity and Phase-Specific Biomarker in Cocaine Use Disorder.

Cocaine Use Disorder (CUD) is one of the diseases with the greatest social and health impact, due to the high cost of rehabilitation management and the high risk of dangerous behavior and relapse. This pathology frequently leads to unsuccessful attempts to interrupt the consumption, resulting in relapses and a vicious cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/ anticipation (craving). The alternation of these phases in addiction was well illustrated by Koob and colleagues in the so-called "addictive cycle", which nowadays represents a landmark in the addiction field. Recently, there has been a surge of interest in the worldwide literature for biomarkers that might explain the different stages of addiction, and one of the most studied biomarkers is, without a doubt, Brain-derived Neurotrophic Factor (BDNF). In this perspective article, we discuss the potential role of BDNF as biomarker of the CUD phases described in the "Addictive Cycle", speculating about the close relationship between BDNF fluctuations and the clinical course of CUD. We also discuss BDNF's potential role as "staging" biomarker, predicting the progression of the disease. Finding valuable biomarkers of CUD severity and disease stage could shift clinicians' focus away from behavioral symptomatic treatment and toward a novel brain-based approach, allowing for the development of more effective and targeted therapeutic strategies, thus determining major benefits for CUD patients.

Impact of sleep disorders and disease duration on neurotrophins levels in cocaine use disorder

IntroductionBrain-derived neurotrophic factor (BDNF) and its precursor proBDNF contribute to brain plasticity and neuronal remodeling. Recently, the ratio between proBDNF and BDNF (RpB) has been proposed as a possible marker in major psychiatric disorders. Convergent lines of evidence suggest neurotrophins alterations could be involved into the pathophysiology of Cocaine Use Disorder (CUD) and insomnia. The aims of the present study are to evaluate the correlations between neurotrophins levels, insomnia and clinical features among CUD patients. Materials and methodsSubjects with a moderate to severe CUD were recruited. ProBDNF, BDNF and consequently RpB values were analyzed using ELISA technique. Insomnia severity index (ISI) scale was used to assess the severity of insomnia. Sociodemographic characteristics and CUD habits (e.g., years of cocaine use) were also collected. ResultsTwenty-four subjects (mean age 39.3 ± 6.7 years) were recruited. Correlation analysis showed that lower values of RpB were associated with higher ISI score (r = −0.469; p = 0.021), longer history of cocaine use (r = −0.584, p = 0.022) and higher amount of cocaine used (r = −0.655, p = 0.004). DiscussionThese preliminary findings may offer a novel insight on neurobiological alterations sustaining cocaine use. Lower RpB, as observed both in high insomnia levels and in chronic cocaine use, could induce a neuroprotective state as a synaptic homeostatic response to chronic damage. These findings also highlight the important role of neurotrophins balance on neurobiological alterations induced by cocaine misuse and insomnia, suggesting that RpB could be considered as a marker of neurotrophic and metabolic state of neural tissue.

I can’t wait! An investigation into time processing in cocaine use disorder

IntroductionAlmost all definitions of impulsivity include the notion of distorted time perception such as impaired awareness of the future or premature responses. Preclinical evidence suggests that stimulant drugs speed up the internal clock, making time pass faster than it actually is. However, stimulant-addicted humans, who are drug-abstinent seem to over-estimate long time intervals.ObjectivesThe present study aims to investigate time processing in actively using patients with cocaine use disorder (CUD). We hypothesise that active cocaine use will be associated with an under-estimation of long time intervals.MethodsWe recruited 48 men with a chronic history of cocaine use, meeting the DSM-5 criteria for CUD, and 42 healthy men without a history of substance use disorders. All participants completed a time reproduction task in which they were presented four times with six different time durations and were subsequently asked to reproduce them by pressing the space bar for the same time duration of the target interval they had just seen. Participants also completed the Barratt Impulsiveness Scale (BIS-11).ResultsOverall precision in time reproduction was significantly reduced in CUD patients (F6,81=3.97,p=0.002), which was particularly evident for longer time delays. CUD patients’ estimated-to-target-duration ratios were marginally shorter for the 11000ms (F1,86=3.1,p=0.084) and significantly shorter for the 18000ms and 24000ms time intervals (both p&lt;0.05). Time reproduction performance correlated with self-reported attentional impulsivity on the BIS-11 in both CUD patients and healthy controls (all p&lt;0.05).ConclusionsConsistent with preclinical work, the inner clock of humans with regular cocaine use seems to be accelerated.DisclosureNo significant relationships.

The Mexican magnetic resonance imaging dataset of patients with cocaine use disorder: SUDMEX CONN

Cocaine use disorder (CUD) is a substance use disorder (SUD) characterized by compulsion to seek, use and abuse of cocaine, with severe health and economic consequences for the patients, their families and society. Due to the lack of successful treatments and high relapse rate, more research is needed to understand this and other SUD. Here, we present the SUDMEX CONN dataset, a Mexican open dataset of 74 CUD patients (9 female) and matched 64 healthy controls (6 female) that includes demographic, cognitive, clinical, and magnetic resonance imaging (MRI) data. MRI data includes: 1) structural (T1-weighted), 2) multishell high-angular resolution diffusion-weighted (DWI-HARDI) and 3) functional (resting state fMRI) sequences. The repository contains unprocessed MRI data available in brain imaging data structure (BIDS) format with corresponding metadata available at the OpenNeuro data sharing platform. Researchers can pursue brain variability between these groups or use a single group for a larger population sample.

Detecting Small Vessel Pathology in Cocaine Use Disorder.

BackgroundCocaine use is associated with an increased risk of cerebrovascular accidents. Small vessel pathology has been linked to the risk of stroke in cocaine users, but can be challenging to detect on conventional magnetic resonance (MR) scans. Fluid-attenuated inversion recovery (FLAIR) scans permit better resolution of small vessel lesions.ObjectivesFLAIR scans are currently only acquired based on the subjective judgement of abnormalities on MR scans at face value. We sought to evaluate this practice and the added value of FLAIR scans for patients with cocaine use disorder (CUD), by comparing microbleeds detected by MR and FLAIR scans. We hypothesised that microbleeds are more pronounced in CUD patients, particularly so in participants who had been selected for a FLAIR scan by radiographers.MethodsSixty-four patients with CUD and 60 control participants underwent a brain scan. The MR of 20 CUD patients and 16 control participants showed indicators of cerebral infarction at face value and were followed up by a FLAIR scan. We determined the volume of microbleeds in both MR and FLAIR scans and examined associations with various risk factors.ResultsWhile MR lesion volumes were significantly increased in CUD patients, no significant differences in lesion volume were found in the subgroup of individuals who received a FLAIR.ConclusionThe current practice of subjectively evaluating MR scans as a basis for the follow-up FLAIR scans to detect vascular pathology may miss vulnerable individuals. Hence, FLAIR scans should be included as a routine part of research studies.