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Background Early-life stressful events affect the neurobiological maturation of cerebral circuitries including the endogenous opioid system and the effects elicited by adolescent cocaine exposure on this system have been poorly investigated. Here, we evaluated whether cocaine exposure during adolescence causes short- or long-term alterations in mRNAs codifying for selected elements belonging to the opioid system. Moreover, since brain-derived neurotrophic factor (BDNF) may undergo simultaneous alterations with the opioid peptide dynorphin, we also evaluated its signaling pathway as well. Methods Adolescent male rats were exposed to cocaine (20 mg/kg/day) from post-natal day (PND) 28 to PND42, approximately corresponding to human adolescence. After short- (PND45) or long-term (PND90) abstinence, prodynorphin-κ-opioid receptor (pDYN-KOP) and pronociceptin-nociceptin receptor (pN/OFQ-NOP) gene expression were evaluated in the nucleus accumbens (NAc) and hippocampus (Hip) together with the analysis of BDNF signaling pathways. Results In the NAc of PND45 rats, pDYN mRNA levels were up-regulated, an effect paralled by increased BDNF signaling. Differently from NAc, pDYN mRNA levels were down-regulated in the Hip of PND45 rats without significant changes of BDNF pathway. At variance from PND45 rats, we did not find any significant alteration of the investigated parameters either in NAc and Hip of PND90 rats. Conclusions Our results indicate that the short-term withdrawal from adolescent cocaine exposure is characterized by a parallel pDYN mRNA and BDNF signaling increase in the NAc. Given the depressive-like state experienced during short abstinence in humans, we hypothesize that such changes may contribute to promote the risk of cocaine abuse escalation and relapse.

Objective: Schizophrenia, cocaine-related disorder, antisocial personality disorder, and psychopathy share biological bases, but few studies discriminate between these disorders by means of prepulse inhibition. This work studies the phenotype of patients with cocaine-related disorders who are vulnerable to presenting a dual diagnosis of schizophrenia or antisocial personality disorder, by evaluating their prepulse inhibition, impulsivity and psychopathy personality traits. Methods: The sample (n = 38) was divided into three groups: (1) cocaine-related disorder (8 individuals diagnosed with cocaine-related disorder who did not present any other mental disorder), (2) cocaine-related disorder and schizophrenia (n = 14), and (3) cocaine-related disorder and antisocial personality disorder (n = 16). Results: The prepulse inhibition in the two groups with dual diagnosis was lower than that in the cocaine-related disorder group, F(2, 35) = 6.52, p = .004, while there was no significant differences between the two dual-diagnosis groups. Psychopathy was evaluated with the revised Hare Psychopathy Checklist and showed no correlation with the prepulse inhibition. Secondary psychopathy (impulsivity and poor behavior control), as evaluated with Levenson Self-Report Psychopathy Scale, was related to the prepulse inhibition. Two discriminating functions were obtained that allowed prediction of patient inclusion in the groups using the prepulse inhibition and the revised Hare Psychopathy Checklist with a success rate of 81.6% (cocaine-related disorder = 62.5%; cocaine-related disorder and schizophrenia = 78.6%; cocaine-related disorder and antisocial personality disorder = 93.8%). These results are discussed in regard to the neurobiological implications of prepulse inhibition in dual diagnosis. Conclusions: The results suggest that the prepulse inhibition is a promising dual-diagnosis vulnerability marker in individuals with cocaine addiction, because prepulse inhibition deficits are related both to schizophrenia and antisocial personality disorder. In addition, prepulse inhibition, which is considered a good endophenotype for studies on the genetic and neurobiological basis of cocaine-related disorder and schizophrenia, could be used in the same way in studies on antisocial personality disorder.

Mental health and addiction services have traditionally evolved separately in many European countries, with policy reflecting this. Differences in severity profiles between users of the community addiction services with comorbidities of mental illness and substance misuse and those with substance misuse only were studied using a matched case-control study design, with regard to the main substance (opiates or cocaine) patients were dependent on. Patterns of substance abuse and diagnostic features were evaluated according to the Addiction Severity Index (ASI) and DSM-IV. Mentally ill substance abusers are significantly more likely to have used amphetamines, inhalants and having been polydrug users. They are particularly impaired in medical and family/social relationships ASI composite scores, but less in drug use. Severity profiles and needs of dually diagnosed patients require assessment and treatment skills that should be provided through adequate links with mental health system. Copyright © 2006 S. Karger AG.

In Europe it is estimated that around 13. million of adults (15-64. years) have used cocaine at least once in their lifetime. The most frequently used route of administration for the drug is intranasal inhalation, or "snorting", and thus the adverse effects of cocaine on the nasal tract are very common. Habitual nasal insufflations of cocaine may cause mucosal lesions, and if cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of nose, sinuses and palate that can mimic other diseases such as tumors, infections, and immunological diseases. Thorough diagnostic workup, including endoscopic, radiologic, histopathologic and serologic testing is imperative to arrive at the proper diagnosis and to initiate appropriate local and systemic treatment. Positive antineutrophil cytoplasmic antibody (ANCA) test results may be found in an unexpectedly large proportion of patients with CIMDL. In several instances their lesions are clinically indistinguishable from granulomatosis with polyangiitis (Wegener's) limited to the upper respiratory tract. CIMDL seem to be the result of a necrotizing inflammatory tissue response triggered by cocaine abuse in a subset of patients predisposed to produce ANCA, particularly those reacting with HNE. The presence of these HNE-ANCA seems to promote or define the disease phenotype. CIMDL do not respond well to immunosuppressive therapy. Only the consistent removal of persistent stimuli of autoantibody production (cocaine, bacterial superinfections) can halt the disease process, prevent the progression of the lesions and promise success of surgical repair procedures. © 2012 Elsevier B.V.

Introduction and Aims. Although, in the laboratory, most acute adverse effects of cocaine are dose-dependent and alcohol potentiates some of these effects, there are few observational studies, and scarce awareness that the risk of acute cocaine intoxication (ACI) can increase as the amounts of cocaine and alcohol consumed increase. Our objectives were to assess if the risk of ACI increases with the level cocaine use, both in chronic and binge use; and also to determine whether it increases when a cocaine binge is combined with binge drinking or with regular excessive drinking. Design and Methods. Hypotheses were evaluated using logistic regression and case-crossover analyses in a sample of 720 young regular cocaine users who did not regularly use heroin, recruited at drug scenes in 20042006. All data on ACI, predictor and confounding variables were obtained through a computer-assisted personal interview. Results. The annual prevalence of ACI was 21%. In the last year 10.3% of the participants reported cocaine binges (=0.5 g in 4 h). ACI risk increased considerably in the 4 h following a cocaine binge (odds ratio = 34.6; 95% confidence interval 11.5170.8). Also, it increased with increases in the average level of cocaine used over a long period and when users regularly drank excessively. Finally, the results suggest that the high risk of ACI associated with cocaine binge may increase even more when combined with binge drinking. Discussion and Conclusions. Awareness of the dose-dependent effect of cocaine on ACI risk, as well as the possible synergistic effect of alcohol, ought to be incorporated into preventive and care strategies.[Santos S, Brugal MT, Barrio G, Castellano Y, Domingo-Salvany A, Espelt A, Bravo MJ, de la Fuente L, the ITINERE Project Group. Assessing the effect of patterns of cocaine and alcohol use on the risk of adverse acute cocaine intoxication. Drug Alcohol Rev 2012;31:439446]