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Background and Objectives: 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., Methods: 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., Results: 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)., Discussion and Conclusions: 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., Scientific Significance: 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., (© 2024 The Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry (AAAP).)

Suicide attempts (SA) are prevalent in substance use disorders (SUD). Epigenetic mechanisms may play a pivotal role in the molecular mechanisms of environmental effects eliciting suicidal behaviour in this population. Hypothalamic-pituitary-adrenal axis (HPA), oxytocin and neurotrophin pathways have been consistently involved in SA, yet , their interplay with childhood adversity remains unclear, particularly in SUD. In 24 outpatients with SUDs, we examined the relation between three parental dysfunctional styles and history of SA with methylation of 32 genes from these pathways, eventually analysing 823 methylation sites. Extensive phenotypic characterization was obtained using a semi-structured interview. Parental style was patient-reported using the Measure of Parental Style (MOPS) questionnaire, analysed with and without imputation of missing items. Linear regressions were performed to adjust for possible confounders, followed by multiple testing correction. We describe both differentially methylated probes (DMPs) and regions (DMRs) for each set of analyses (with and without imputation of MOPS items). Without imputation, five DMRs in OXTR, CRH and NTF3 significantly interacted with MOPS father abuse to increase the risk for lifetime SA, thus covering the three pathways. After imputation of missing MOPS items, two other DMPs from FKBP5 and SOCS3 significantly interacted with each of the three father styles to increase the risk for SA. Although our findings must be interpreted with caution due to small sample size, they suggest implications of stress reactivity genes in the suicidal risk of SUD patients and highlight the significance of father dysfunction as a potential marker of childhood adversity in SUD patients., (© 2024 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10 -3 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10 -3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal., (© 2022 Society for the Study of Addiction.)

Aims: We explored lifetime comorbidities in clinical subsamples with a diagnosis of Psychosis (N = 143), bipolar (BD = 511), and unipolar disorders (UP = 861)., Methods: We analyzed trajectories and patterns of comorbidities using novel metrics, namely bubble plots and density of antecedent events per year of illness exposure per individual., Results: Age at onset (AAO) of most comorbidities was similar to epidemiological studies, but cumulative rates were higher in clinical cases. There were some between group differences in patterns or burden of comorbidities, for example, Psychosis showed the earliest AAO of any mental disorder; UP showed the latest AAO of the index diagnosis. The relative risk of multimorbidity was lower in UP compared with other diagnoses, however, the goodness of fit for the illness trajectory path was lowest for BD., Conclusions: Bubble plots offer a useful representation of timing, sequence, cumulative probability and of comorbidities, the added value of reporting density measures was less obvious., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: The prevalence of cognitive impairment is high among alcohol-dependent patients. Although the clinical presentation of alcohol-related cognitive disorder (ARCD) may resemble that of Alzheimer's disease (AD), the prognosis and treatment of the 2 diseases are different. Cerebrospinal fluid (CSF) biomarkers (tau, phosphorylated tau, and amyloid β) have high diagnostic accuracy in AD and are currently being used to discriminate between psychiatric disorders and AD, but are not used to diagnose ARCD. The aim of this study was to characterize CSF biomarkers in a homogeneous, cognitively impaired alcohol-dependent population., Methods: This single-center study was conducted in an addiction medicine department of a Parisian Hospital. We selected patients with documented persistent cognitive impairment whose MoCA (Montreal Cognitive Assessment) score was below 24/30 after at least 1 month of documented inpatient abstinence from alcohol. We measured the CSF biomarkers (tau, phosphorylated tau, and amyloid β 1-42 and 1-40) in 73 highly impaired alcohol-dependent patients (Alcohol Use Disorders Identification Test score over 11 for women and 12 for men) with., Results: Patients' average age was 60 ± 9.1 years and 45 (61.6%) had a normal CSF profile, 8 (11.0%) had a typical CSF AD profile, and 20 (27.4%) had an intermediate CSF profile., Conclusions: This study revealed a high prevalence of AD in alcohol-dependent patients with persistent cognitive deficits and several anomalies in their CSF profiles. Thus, it is important to consider AD in the differential diagnosis of persistent cognitive deficits in patients with alcohol dependence and to use CSF biomarkers in addition to imaging and neuropsychological testing to evaluate alcohol-related cognitive impairment., (© 2021 by the Research Society on Alcoholism.)

For several decades, studies conducted to evaluate the efficacy of RS(±)-Baclofen in the treatment of alcohol dependence yielded contrasting results. Human and animal studies recently questioned the use of the racemic drug in patients since a potential important role of the different enantiomers has been revealed with an efficacy thought to reside with the active R(+)-enantiomer. Here we conducted experiments in the postdependent rat model of alcohol dependence to compare the efficacy of R(+)-Baclofen or S(-)-Baclofen to that of RS(±)-Baclofen on ethanol intake, seeking, and relapse. R(+)-Baclofen was more effective than RS(±)-Baclofen in reducing ethanol intake and seeking during acute withdrawal and during relapse after abstinence. We also used an original population approach in order to identify drug responders. We found a significant proportion of responders to S(-)-Baclofen and RS(±)-Baclofen, displaying an increase in ethanol intake, and this increasing effect on alcohol intake was not seen in the R(+)-Baclofen group. At an intermediate dose of R(+)-Baclofen, devoid of any motor side effects, we identified a very large proportion of responders (75%) with a large decrease in ethanol intake (90% decrease). Finally, the response to RS(±)-Baclofen on ethanol intake was correlated to plasma level of Baclofen. R(+)-Baclofen and RS(±)-Baclofen were effective in reducing sucrose intake. Our study has important clinical implication since it suggests that the wide variability in the therapeutic responses of patients to RS(±)-Baclofen may come from the sensitivity to the R(+)-Baclofen but also to the one of the S(-)-Baclofen that can promote an increase in ethanol intake., (© 2020 Society for the Study of Addiction.)

Background: Inpatient alcohol detoxifications are only proposed after motivational outpatient encounters because detoxification directly from the emergency department (ED) is believed to be associated with early dropout and poor adherence to outpatient follow-up. The aim of this prospective follow-up study was to test the feasibility of unscheduled (UP) alcohol detoxification directly from the ED and to compare the 1-year follow-up of these patients to that of scheduled (SP) patients., Methods: A quasi-naturalistic prospective follow-up study of 120 patients: 60 consecutively admitted patients referred directly by the ED for alcohol detoxification (UP) were compared to 60 consecutively admitted patients who had undergone the usual preparation for an inpatient detoxification program (SP). The length of hospitalization (in days) and attendance to postdischarge outpatient visits during the first year was compared., Results: UP patients were older, less frequently employed, and had more somatic comorbidities compared with SP patients. The UP length of stay was significantly longer (20 ± 16 vs. 14 ± 6, p = 0.04). No difference in their postdischarge attendance was observed; the number of patients attending 1 session (57% UP vs. 65% SP, p = 0.227) and 5 sessions (22% UP vs. 32% SP, p = 0.151) and the mean number of postdischarge visits attended were comparable between the UP and SP groups (2.7 ± 6 vs. 4.5 ± 6; Mann-Whitney U = 1,517, p = 0.124)., Conclusions: We did not find that UP patients who had been admitted for alcohol detoxification had a significantly higher dropout rate or lower postdischarge addiction treatment attendance. Because they may have several advantages, detoxification programs directly linked with EDs should be further evaluated., (Copyright © 2016 by the Research Society on Alcoholism.)

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., (© American Academy of Addiction Psychiatry.)

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., (© American Academy of Addiction Psychiatry.)

Aims: Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients., Methods: Eighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day(-1) methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes., Results: Methadone maintenance dose was correlated to the highest dose ever used (r(2) = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27-18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01-2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day(-1) in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs ] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = -0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose., Conclusions: Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP3A4 activity in stable patients., (© 2015 The British Pharmacological Society.)

This study aimed to develop a scale (Obsessive-Compulsive Cocaine Scale [OCCS]) for measuring cocaine craving based on the Obsessive Compulsive Drinking Scale (OCDS). We tested the scale on 116 French-speaking cocaine users. The scale was reliable (Cronbach's α= 0.93). It was significantly correlated with a visual analogue scale of craving (r = 0.641, p < .001) and discriminated between cocaine-dependant subjects (score 36 ± 11) and abusers (score 17 ± 9, p < .001). Prospective tests on a sample of 20 subjects showed that the OCCS score changed over 3 weeks of treatment and was significantly correlated with the visual analogue scale of craving (r = 0.492, p = .038). Principal component analysis identified three factors: resistance, intensity, and interference. The OCCS questionnaire could be used to repeatedly assess cocaine craving in prospective studies in cocaine addicts. (Am J Addict 2012;00:1-7)., (Copyright © American Academy of Addiction Psychiatry.)

Cocaine use is associated with the occurrence of transient psychotic symptoms. Sixteen poly-substance abusers already in treatment, who were diagnosed with crack dependence, were assessed twice: at baseline and after 3 weeks of medical management specifically aimed at cocaine abstinence. The psychotic symptoms were assessed with the French version of the Scale for Assessment of Positive Symptoms-Cocaine-Induced Psychosis (SAPS-CIP). There was a decrease of both cocaine intake and psychotic symptoms at week 3 (Wilcoxon's Z, p < .001 and .028, respectively). Furthermore, there was a significant correlation between psychotic symptoms and dose reduction (r(2) = .49, Spearman's ρ= .613, p < .012)., (Copyright © American Academy of Addiction Psychiatry.)

The aim of this study was to evaluate the psychometric properties of the French version of the Marijuana Effect Expectancy Questionnaire (48 items) and study the cannabis expectancies according to the patterns of substance use and psychiatric disorders (DSM-IV). A sample of 263 subjects (average age 33.1 years [SD = 8.7], 56% men) consisting of cannabis users (n = 64), psychiatric inpatients (n = 175, most of whom were hospitalized for withdrawal), and a control group (n = 24) completed the questionnaire. Internal reliability was good (α= .87) and temporal reliability was satisfactory, with 24 of 48 items having a significant κ ≥ .41. Factor analysis showed four main factors that explained 42.1% of the total variance. The women feared Cognitive Impairment and Negative Effects, and Negative Behavioral Effects more than the men. The onset age of cannabis use, onset age of abuse, abuse and dependence were associated with fewer negative expectancies. Cannabis dependents differed from abusers by more Relaxation and Social Facilitation expectancies. Patients with major depressive episodes, panic disorder, social anxiety disorder, or posttraumatic stress disorder feared negative effects the most. Schizophrenic patients expected more Perceptual Enhancement and Craving. The French version of the Marijuana Effect Expectancy Questionnaire has good psychometric properties and is valid to assess cannabis expectancies in adolescents and adults with substance use disorders., (Copyright © American Academy of Addiction Psychiatry.)