A specific cognitive behavioral group therapy program for stimulant use disorder.

Introduction: Stimulant use is an important health issue. In the US in 2018, 2.8% of males and 1.5% of females older than 18 had used cocaine in the preceding 12 months. Objective: To intervene in a specific targeted group of Stimulant Use Disorder (SUD) patients according to CBT and relapse prevention theories, and to determine the program's feasibility and attendance. Method: Stimulant Use Disorder patients in addiction care were evaluated for addictive, psychological and psychiatric dimensions at baseline and conclusion in a 9-session CBT group program with several themes: define SUD, enhance motivation, involve close companions, cope with craving, decline a proposal, solve problems, invite expert patients, invest time and money, and review content. Results: In total, 41 patients attended at least one session. They were mainly poly dependent, primarily cocaine users. Sixty percent of the population also suffered from another psychiatric comorbidity. Median attendance for participants was 7/9 sessions. Conclusion: A specific targeted CBT group for stimulant dependent highly comorbid patients is feasible. These findings suggest that peers should be included in addiction care services.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Feasibility of an Extensive Strategy for Adult Diagnosis of Attention Deficit Hyperactivity Disorder Among Patients Suffering From Substance Use Disorders.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is found in up to 20% adults with Substance Use Disorder (SUD). ADHD + SUD is associated with a more complex clinical presentation and poorer outcomes than each disorder alone. In the presence of SUD, adult ADHD is particularly difficult to diagnose as both disorders can mimic or hide the symptoms of each other. Our university hospital in Paris recently started an extensive outpatient diagnostic procedure for adult patients with SUD to ascertain or refute ADHD diagnosis and to provide therapeutic guidance. Here, we report the acceptability of the assessment procedure for patients and the preliminary description of the current and lifetime clinical profiles as a function of the final diagnosis "ADHD vs. no ADHD." Method: Adult SUD patients with suspected ADHD were included in the current pilot study after stating they had no objection that their de-identified data were used for research purposes, according to French ethical procedures. Patients were evaluated for ADHD, comorbid mental disorders, cognitive state and dimensional psychological variables. They were assessed by trained psychologists and psychiatrists using standardized tools over a day. ADHD diagnosis was mainly based on the Diagnostisch Interview Voor ADHD for DSM-5 (DIVA-5). Results: Out of 18 eligible patients, 17 were included in the cohort (1 excluded) and none was opposed to using their data. Thirteen (76%) participants were diagnosed with ADHD. All patients appointed for the ADHD diagnostic procedure came, respected schedules and finished the evaluation. All patients were impaired on cognitive functioning and were highly comorbid, but ADHD patients seems to suffer even more from those conditions, especially for cannabis and stimulant use disorders. Discussion: Preliminary results show high acceptability of the procedure by ADHD-SUD patients. This result could be explained by all the organization adapted to the psychopathology. Patients' baseline motivation to participate also represents an uncontrolled variable that could promote the ability to follow the procedure. Acceptance results of the protocol are promising and represent a starting point to identify the best procedures to design patient-centered pharmacological and non-pharmacological therapies.

Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors.

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity. METHODS: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately. RESULTS: Cocaine dependence (poccurrence= 6.18 × 10-5, pseverity= 9.25 × 10-8), number of cocaine dependence DSM IV-Tr criteria (poccurrence= 1.22 × 10-7, pseverity= 5.09 × 10-6), and frequency of intake during the worst period of misuse (poccurrence= 8.51 × 10-04, pseverity= 0.04) were associated with greater occurrence and higher severity of CIH. The genetic associations did not yield significant results after correction for multiple tests. However, some nominal associations of SNPs mapped to the VMAT2, DBH, DRD1, and DRD2 genes were significant. In the multivariate model, the significant variables were the number of cocaine dependence criteria, lifetime alcohol dependence, and the nominally associated SNPs. CONCLUSION: Our study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background.

Childhood trauma and the severity of past suicide attempts in outpatients with cocaine use disorders.

Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method: 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results: 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p = 9 × 10-7). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion: These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.

Influence of Clinical Markers of Dopaminergic Behaviors on Depressive Symptoms During Withdrawal in Cocaine Users.

Background: During cocaine withdrawal, transient depressive symptoms that do not meet the criteria for depression, but promote relapse, are frequently observed. Their temporality could evoke a role of dopamine, especially since the underlying mechanism of these depressive symptoms is not well understood. We hypothesized that variation in the dopaminergic activity profile, modeled from clinical markers, could be implicated in the development of depressive symptoms during cocaine withdrawal. Methods: We compared patients reporting depressive symptoms (RDS+) or not (RDS-) during cocaine withdrawal. We evaluated dopaminergic activity through indirect clinical markers based on the known dopaminergic behaviors. A combined criterion was constructed for hyper and hypo dopaminergic models according to the O'Brien method and illustrated by the Hedges' effect-size and forest-plot graph. A multidimensional factorial analysis was carried out to determine which parameters discriminate RDS+/RDS- patients. Results: 313 patients were included, and 77% reported depressive symptoms during cocaine withdrawal. Hyperdopaminergic variables used to discriminate the two groups had a large overall effect size (-0.669) and included psychotic symptoms (-0.524), hallucinations (-0.548), and delusions (-0.528). The overall effect of the hypodopaminergic component was considerable (-0.604) with a large effect size for the severity of dependence (-0.616), withdrawal symptoms (-0.578), and anhedonia (-0.528). The combined model including hyperdopaminergic and hypodopaminergic components had the largest effect size (-0.785). Conclusion: The dopaminergic activities profile, assessed by indirect clinical markers, seems to characterize patients with depressive symptoms very well during cocaine withdrawal. RDS+ patients reported moreover higher levels of psychotic symptoms and more severe cocaine use disorder than RDS-.

Risk and Protective Factors of Lifetime Cocaine-Associated Chest Pain.

Introduction: Cocaine users often present with repetitive events of cocaine-associated chest pain (CACP), clinically resembling acute coronary syndromes. The aim of the study is to describe the specific risk factors for CACP. Method: Cocaine users (n = 316) were recruited for a multicenter cross-sectional study. Lifetime CACP history, sociodemographic factors, and lifetime use of cocaine and other substances were assessed. Thirty single nucleotide polymorphisms (SNPs) of NOS3, ROCK2, EDN1, GUCY1A3, and ALDH2 genes, suggested by the literature on coronary spasms, were selected. The associations with CACP history were tested using the chi-square test, Student's t-test and logistic regression. Results: Among the 316 subjects [78.5% men, mean age 37.5 years, (standard-deviation ±8.7)], 190 (60.1%) were daily cocaine users and 103 (32.6%) reported a lifetime CACP history. Among those with a lifetime CACP history, the median was 10 events per individual. In multivariate analysis, lifetime CACP history was associated with daily cocaine use [odds-ratio (OR) 3.24; 95% confidence intervals (1.29-9.33)], rapid route of cocaine use [OR 2.33 (1.20-4.64) vs. intranasal use], and lifetime amphetamine use [daily amphetamine use: OR 2.80 (1.25-6.32) and non-daily amphetamine use: OR 2.14 (1.15-4.04) vs. never used]. Patients with lifetime opioid maintenance treatment (OMT) reported significantly less lifetime CACP history [OR 0.35 (0.16-0.76)]. None of the selected SNPs was associated with CACP history after multiple testing corrections. Conclusions: Clinical variables describing the intensity of stimulant use were positively associated with lifetime CACP history, while OMT was negatively associated with it. Specific harm reduction strategies can target these risk factors.

Clustering suicidal phenotypes and genetic associations with brain-derived neurotrophic factor in patients with substance use disorders.

Suicide attempts (SA), especially recurrent SA or serious SA, are common in substance use disorders (SUD). However, the genetic component of SA in SUD samples remains unclear. Brain-derived neurotrophic factor (BDNF) alleles and levels have been repeatedly involved in stress-related psychopathology. This investigation uses a within-cases study of BDNF and associated factors in three suicidal phenotypes ('any', 'recurrent', and 'serious') of outpatients seeking treatment for opiate and/or cocaine use disorder. Phenotypic characterization was ascertained using a semi-structured interview. After thorough quality control, 98 SNPs of BDNF and associated factors (the BDNF pathway) were extracted from whole-genome data, leaving 411 patients of Caucasian ancestry, who had reliable data regarding their SA history. Binary and multinomial regression with the three suicidal phenotypes were further performed to adjust for possible confounders, along with hierarchical clustering and compared to controls (N = 2504). Bayesian analyses were conducted to detect pleiotropy across the suicidal phenotypes. Among 154 (37%) ever suicide attempters, 104 (68%) reported at least one serious SA and 96 (57%) two SA or more. The median number of non-tobacco SUDs was three. The BDNF gene remained associated with lifetime SA in SNP-based (rs7934165, rs10835210) and gene-based tests within the clinical sample. rs10835210 clustered with serious SA. Bayesian analysis identified genetic correlation between 'any' and 'serious' SA regarding rs7934165. Despite limitations, 'serious' SA was shown to share both clinical and genetic risk factors of SA-not otherwise specified, suggesting a shared BDNF-related pathophysiology of SA in this population with multiple SUDs.

Network analysis of psychotic manifestations among cocaine users.

Psychotic experiences can be described along a continuum ranging from no psychotic experience at all, to clinical psychotic disorder. Any individual in the general population may encounter psychotic experiences under certain circumstances. Transient Cocaine Induced Psychotic Symptoms (TCIPS) are a well described model of such circumstances. Therefore, our aim was to use a network analysis to get a better knowledge on the architecture of previously described risk factors and how they contributed to two different measures of psychosis (psychosis proneness and transient cocaine induced psychotic symptoms) This study is a secondary analysis conducted among 180 cocaine users in addiction care centers in Paris and Paris suburb, who were evaluated with the PDI (Peters Delusion Inventory) and the SAPS-CIP (Scale for the Assessment of Psychotic Symptoms - Cocaine Induced Psychosis). Schizophrenia diagnosis was extracted from medical record. Relevant variables significantly associated with SAPS-CIP total score or PDI at the first step were included in a network analysis to better figurate their respective associations. The network centrality measures showed that the product preferentially used (crack vs cocaine) was related to TCIPS, psychosis proneness and, to a lesser extent, schizophrenia. Secondly, in this model TCIPS is a mediator between intensive cocaine use and psychosis proneness. Thirdly, this study refines the previous knowledge on heavy cannabis use being a risk factor for TCIPS. The observed link is not direct but mediated by psychosis proneness.

Chronic exposure to cocaine is associated with persistent behavioral disturbances. A cross-sectional dimensional study in outpatients with multiple substance use disorders.

RATIONALE: Behavioral disturbances (BD) are prevalent in patients with substance use disorders (SUD). OBJECTIVES: To test the hypothesis that chronic exposure to cocaine could favor the acquisition of BD that were not present in childhood. METHODS: We used child and adult ADHD self-report screening scales (WURS-25 and ASRS-6, respectively, with their usual threshold) as assessment tools for significant BD. In a cross-sectional assessment of 382 patients with multiple SUD, we investigated BD and then "de novo" BD (i.e., by restricting the sample to patients below the threshold for childhood BD) (N = 214). We also tested for a gradient effect between patients' lifetime DSM IV cocaine and opioid dependence status and the prevalence of BD. RESULTS: BD were found in 188/382 (42.9%) subjects and in 74/214 (34.6%) subjects. Three clinical factors were associated with BD in the whole sample: the number of cocaine dependence criteria (OR = 1.36 [1.14-1.64], p = 0.001), the number of opioid dependence criteria (OR = 0.69 [0.52-0.91], p = 0.010), and a personal history of using cocaine through rapid routes of administration (OR = 0.41 [0.19-0.88], p = 0.022). The same three factors were associated with "de novo" BD in the restricted sample: OR = 1.35 ([1.11-1.63], p = 0.002), OR = 0.83 ([0.70-0.99], p = 0.046), and OR 0.37 ([0.16-0.86], p = 0.022), respectively. There were significant gradients for BD according to the cocaine exposure categories in the whole (Mantel-Haenszel, p < 0.001) and in the restricted sample (Mantel-Haenszel, p = 0.002). CONCLUSIONS: Cocaine exposure was positively associated with behavioral disturbances in a dose-dependent manner in this clinical sample, whilst opioid exposure showed a negative association.

Relevance of treated cocaine users' retrospective memory of first cocaine use.

Little is known regarding between-subject variability in the subjective effects of first cocaine use. This study retrospectively assesses the subjective effects of first cocaine use in 160 current treatment-seeking cocaine use disorder patients. Subjective effects of first cocaine use were evaluated with an ad-hoc questionnaire used for cannabis effects. A principal component analysis (PCA) was performed, with resulting factors correlated with clinical variables (α = 0.05). Four factors emerged in the PCA, namely Anxiety (accounting for 21.5% of questionnaire variance), Disinhibition (17.3%), Tachypsychia (16%) and Calmness (13%). Male gender was associated with Disinhibition and Tachypsychia. Cocaine severity factors were associated with Disinhibition, Tachypsychia and Calmness. Opiate, sedative and poppers uses were associated with Anxiety, Tachypsychia and Calmness. The retrospective assessment of the subjective effects of first cocaine use shows significant variability. The different dimensions of subjective first effects are influenced by age, gender and previous substance use history, as well as characteristics of first cocaine use and cocaine-related outcomes.

Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

Self-reported cue-induced physical symptoms of craving as an indicator of cocaine dependence.

BACKGROUND: The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians. OBJECTIVE: To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could be a useful way to boost the diagnosis of cocaine dependence. METHODS: A cross-sectional study of 221 cocaine users from several outpatient addiction treatment services in France, addressing the most severe period of cocaine use. DSM-IV cocaine dependence was determined with the MINI International Neuropsychiatric Interview (MINI). Physical symptoms before using cocaine were retrospectively assessed with a single item rated on a 0-5 scale. RESULTS: The prevalence of DSM-IV cocaine dependence was 84.6%. The mean score on the physical symptoms item was 1.3 (SD 1.3). A cut-off score of ≥ 1 on this item alone resulted in a sensitivity of 62%, a specificity of 88.2%, a positive predictive value of 96.6% and a negative predictive value of 29.7% to detect DSM IV cocaine dependence in this sample. Adding this item to a model with the frequency of cocaine use significantly increased the predictive power: Nagelkerke's R(2) increased from .149 to .326 (p < .001). DISCUSSION AND CONCLUSION: Recalling past experiences of cue-induced physical signs of cocaine craving is associated with a clinical diagnosis of lifetime cocaine dependence and could be a simple way to improve its detection in clinical settings.

A cannabinoid receptor 1 polymorphism is protective against major depressive disorder in methadone-maintained outpatients.

BACKGROUND AND OBJECTIVES: The burden of opiate dependence not only relies on somatic complications such as infectious diseases or acute intoxication but also on frequent psychiatric events such as major depressive disorder (MDD) and suicidal behavior (SB). Given the preclinical and clinical evidence regarding the associations between cannabinoid systems and both opiate dependence and psychiatric disorders, we chose to address whether one single nucleotide polymorphism (SNP) of the cannabinoid receptor type 1 gene (CNR1) named rs2023239 would be associated with lifetime MDD and SB in a population of opiate-dependent outpatients remitted under stable methadone treatment. METHODS: Sociodemographic and clinical data were included as independent factors in two logistic regression models aimed at predicting SB and MDD, respectively, performed with 85 Caucasian individuals. RESULTS: The minor C allele of rs2023239 showed an independent protective effect against lifetime MDD after adjustment for potential confounders. It was not associated with variables related to suicidal behavior. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Despite limitations due to the modest sample size, our results are consistent with previous research on the endocannabinoid system and suggest new leads for detecting subjects at risk of MDD, which remains insufficiently diagnosed and treated in patients suffering from severe addictive disorders.

Childhood trauma are not associated with the intensity of transient cocaine induced psychotic symptoms.

A personal history of childhood trauma has been associated with the severity of psychotic symptoms in several disorders. We evaluated retrospectively cocaine-induced psychotic symptoms with the SAPS-CIP and childhood trauma with the CTQ in a clinical sample of 144 cocaine users. The SAPS-CIP score was not statistically associated with the presence or number or intensity of trauma, but was associated with rapid routes of administration (intravenous and smoked) and with frequent cocaine use.