Search

Background: Cocaine abuse is capable of activating the innate immune system in the CNS resulting in deregulation of homeostasis between pro and antiinflammatory cytokines. The aim of this study was to investigate serum levels of pro and antiinflammatory cytokines, IL-6 and IL-10 respectively, in cocaine users from a young population-based sample., Methods: This is a case-control study nested in a cross-sectional population-based survey, with individuals of 18 and 35 years old. Two groups were selected: 24 healthy controls and 12 subjects who reported cocaine use. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit., Results: There was a statistically significant increase in IL-6 (p=0.037) and decrease in IL-10 (p=0.007) serum levels, between cocaine users and the control group. There was also an increase in the ratio IL-6/IL-10 (p=0.013) among cocaine users individuals, when compared to the control group., Conclusions: Our results suggest that cocaine users showed an activation of the immune system when compared a control group, demonstrating a disruption in the balance of pro and antiinflammatory cytokines. Thus, peripheral cytokines may represent a putative biomarkers for cocaine users, contributing to the development of diagnosis and effective treatments., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Prenatal cocaine exposure (PCE) is associated with increased rates of illicit-substance use during adolescence. In addition, both PCE and illicit-substance use are associated with alterations in cortico-striato-limbic neurocircuitry, development of which is ongoing throughout adolescence. However, the relationship between illicit-substance use, PCE and functional neural responses has not previously been assessed concurrently., Methods: Sixty-eight adolescents were recruited from an ongoing longitudinal study of childhood and adolescent development. All participants had been followed since birth. Functional magnetic resonance imaging (fMRI) data were acquired during presentation of personalized stressful, favorite-food and neutral/relaxing imagery scripts and compared between 46 PCE and 22 non-prenatally-drug-exposed (NDE) adolescents with and without lifetime illicit-substance use initiation. Data were analyzed using multi-level ANOVAs (pFWE<.05)., Results: There was a significant three-way interaction between illicit-substance use, PCE status and cue condition on neural responses within primarily cortical brain regions, including regions of the left and right insula. Among PCE versus NDE adolescents, illicit-substance use was associated with decreased subcortical and increased cortical activity during the favorite-food condition, whereas the opposite pattern of activation was observed during the neutral/relaxing condition. Among PCE versus NDE adolescents, illicit-substance use during stress processing was associated with decreased activity in cortical and subcortical regions including amygdala, hippocampus and prefrontal cortex. Neural activity within cortico-striato-limbic regions was significantly negatively associated with subjective ratings of anxiety and craving among illicit-substance users, but not among non-users., Conclusions: These findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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: Bilateral and simultaneous lower extremity amputations unrelated to diabetes and peripheral vascular disease are uncommon, although they may be necessary in patients with severe blast injuries. Such amputations, however, usually are performed in patients who are able to understand and consent to the treatment., Case Description: We present the case of a 29-year-old woman who experienced drug-induced psychosis and underwent substantial hypothermic injuries; most notably, irreversible frostbite injuries to both lower extremities, leading to dry and mummified gangrene. As a result of her psychiatric illness, fluctuating catatonic state, and lack of insight into her clinical condition, she was deemed incapable of making decisions regarding her medical care and her mother was made substitute decision maker. The orthopaedic service was consulted regarding possible surgical treatment of her gangrenous feet that were stable and aseptic after limb preservation efforts (including hyperbaric oxygen) had been tried without success. They recommended close clinical monitoring and continued psychiatric treatment. The family, including the substitute decision maker, citing the patient's best interest, rejected the recommendations of the surgical team and demanded immediate surgical transtibial amputation of both lower legs., Literature Review: To our knowledge, such a unique case has not been reported., Clinical Relevance: We examined the decision-making process, the difficulties of caring for such a patient, and the ethical issues that arose.

Delay discounting, which refers to the phenomenon that rewards decrease in subjective value as the delay associated with their receipt increases, is a paradigm that has been used extensively in substance abuse research to understand impulsive decision making. One common measure to assess delay discounting is the Monetary Choice Questionnaire (MCQ) developed by Kirby, Petry, and Bickel (1999). While the MCQ has great utility because of its simplicity and brief administration time, it is possible that the MCQ produces a ceiling effect in estimating delay discounting parameters in highly impulsive individuals. In the present study, we adapted the MCQ to attempt to address this ceiling effect by extending the original scale with 9 items, and we then compared scores on the original MCQ with the extended MCQ in a sample of active cocaine users. The ceiling effect, while observed in the original MCQ scores for over a quarter of the sample, was largely eliminated with the extended scale. Highly impulsive participants, whose scores on the extended scale exceeded the highest possible score on the original scale, had higher levels of sensation seeking compared to other participants, but not trait impulsivity. The extended MCQ may be useful in populations with high rates of impulsivity, where the original measure may underestimate discounting rates due to a ceiling effect., ((c) 2016 APA, all rights reserved).)

Biosensor systems are increasingly promoted for use in behavioral interventions. Portable biosensors might offer advancement over self-report use and can provide improved opportunity for detection and intervention in patients undergoing drug treatment programs. Fifteen participants wore a biosensor wristband capable of detecting multiple physiologic markers of sympathetic nervous system (SNS) arousal for 30 days. Urine drug screening and drug use self-report were obtained twice per week. A parameter trajectory description method was applied to capture abrupt changes in magnitude of three measures of SNS activity: Electrodermal activity (EDA), skin temperature and motion. Drug use events detected by the biosensor were verified using a triad of parameters: the biosensor data, urine drug screens, and patient self-report of substance use. Twelve positive cocaine urine screens were identified. Thirteen self-reported episodes of cocaine use were recorded. Distinct episodes with biometric parameters consistent with cocaine use were identified on biosensor data. Eleven potential cocaine use episodes were identified by biosensors that were missed by both self-report and drug screening. Study participants found mobile biosensors to be acceptable, and compliance with the protocol was high. Episodes of cocaine use, as measured by supraphysiologic changes in biophysiometric parameters, were detected by analysis of biosensor data in instances when self-report or drug screening or both failed. Biosensors have substantial potential in detecting substance abuse, in understanding the context of use in real time, and in evaluating the efficacy of behavioral interventions for drug abuse.

Background: Cocaine-induced neuroplastic changes may result in a heightened propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of basal neuronal activity, this study assessed alterations in rCBF and related resting state functional connectivity (rsFC) to prospectively predict relapse in patients following treatment for cocaine use disorder (CUD)., Methods: Pseudocontinuous arterial spin labeling functional magnetic resonance imaging and resting blood oxygen level-dependent functional magnetic resonance imaging data were acquired in the same scan session in abstinent participants with CUD before residential treatment discharge and in 20 healthy matched control subjects. Substance use was assessed twice weekly following discharge. Relapsed participants were defined as those who used stimulants within 30 days following treatment discharge (n = 22); early remission participants (n = 18) did not., Results: Voxel-wise, whole-brain analysis revealed enhanced rCBF only in the left posterior hippocampus (pHp) in the relapsed group compared with the early remission and control groups. Using this pHp as a seed, increased rsFC strength with the posterior cingulate cortex (PCC)/precuneus was seen in the relapsed versus early remission subgroups. Together, both increased pHp rCBF and strengthened pHp-PCC rsFC predicted relapse with 75% accuracy at 30, 60, and 90 days following treatment., Conclusions: In CUD participants at risk of early relapse, increased pHp basal activity and pHp-PCC circuit strength may reflect the propensity for heightened reactivity to cocaine cues and persistent cocaine-related ruminations. Mechanisms to mute hyperactivated brain regions and delink dysregulated neural circuits may prove useful to prevent relapse in patients with CUD., (Published by Elsevier Inc.)

Rationale: Stress's role in drug use is supported by retrospective interview and laboratory studies, but prospective data confirming the association in daily life are sparse., Objectives: This study aims to assess the relationship between drug use and stress in real time with ambulatory monitoring., Methods: For up to 16 weeks, 133 outpatients on opiate agonist treatment used smartphones to report each time they used drugs or felt more stressed than usual. They rated stress-event severity on a 10-point scale and as a hassle, day spoiler, or more than a day spoiler. For analysis, stress reports made within 72 h before a reported use of cocaine or opioid were binned into 24-h periods., Results: Of 52 participants who reported stress events in the 72-h timeframe, 41 reported stress before cocaine use and 26 before opioid use. For cocaine use, the severity of stressors, rated numerically (r effect = 0.42, CL95 0.17-0.62, p = 0.00061) and percent rated as "more than a day spoiler" (r effect = 0.34, CL95 0.07-0.56, p = 0.0292)], increased linearly across the three days preceding use. The number of stressors did not predict cocaine use, and no measure of stress predicted opioid use. In ecological momentary assessment (EMA) from the whole sample of 133, stress and drug use occurred independently and there was no overall relationship., Conclusions: EMA did not support the idea that stress is a necessary or sufficient trigger for cocaine or heroin use after accounting for the base rates of stress and use. But EMA did show that stressful events can increase in severity in the days preceding cocaine use.

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

With the increasingly widespread illicit use of cocaine, a broad spectrum of clinical pathologies related to this form of drug abuse is emerging. The most frequently used method of administration of powdered cocaine is intranasal inhalation, or "snorting." Consequently, adverse effects of cocaine on the nasal tract are common. Habitual nasal insufflations of cocaine can cause mucosal lesions. If cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of the septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of the nose, sinuses, and palate and can mimic other diseases such as tumors, infections, and immunological diseases. In the literature currently available, involvement of the craniovertebral junction in the cocaine-induced midline destructive lesions (CIMDLs) has never been reported. The present case concerns a 44-year-old man who presented with long-standing symptoms including nasal obstruction, epistaxis, dysphagia, nasal reflux, and severe neck pain. A diagnosis of CIMDL was made in light of the patient's history and the findings on physical and endoscopic examinations, imaging studies, and laboratory testing. Involvement of the craniovertebral junction in the destructive process was evident. For neurosurgical treatment, the authors considered the high grade of atlantoaxial instability, the poorly understood cocaine-induced lesions of the spine and their potential evolution overtime, as well as cocaine abusers' poor compliance. The patient underwent posterior craniovertebral fixation. Understanding, classifying, and treating cocaine-induced lesions involving the craniovertebral junction are a challenge.

The cardiovascular consequences of cocaine use are numerous and can be severe, with mechanisms of cardiotoxicity unique to cocaine that include sympathomimetic effects, blockade of sodium and potassium channels, oxidative stress and mitochondrial damage, and disruption of excitation-contraction coupling. In combination, these effects increase myocardial oxygen demand while simultaneously decreasing oxygen supply. Cocaine-associated chest pain is particularly common and, in some instances, associated with a more severe cardiac syndrome, such as myocardial infarction, myocardial ischemia, arrhythmia, cardiomyopathy, aortic dissection, or endocarditis. Therapy for cocaine-associated chest pain and myocardial infarction is similar to treatment in non-cocaine users, except for differences in the use of benzodiazepines and phentolamine and avoidance of beta-blockers in the acute setting. In this review, we discuss the most up-to-date literature regarding the mechanisms of cocaine-associated cardiotoxicity and clinical consequences, diagnosis, and treatment; we also discuss relevant controversies while proposing several important areas for future research., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The treatment of cocaine dependence is difficult as no approved pharmacotherapy is available as yet. However, in preclinical and clinical trials, a variety of compounds were tested for suitability as inhibitors of craving for and relapse into the use of cocaine, among these antidepressants, antiepileptics, dopamine agonists, disulfiram, and naltrexone. Nalmefene, a structural derivative of naltrexone, shares with its parent compound approval (granted by the European Medical Agency in 2013) as a medication for the treatment of alcohol addiction in the European Union. It differs from naltrexone by a higher affinity for the δ opioid-receptors and a partial agonistic affinity to the κ opioid-receptors. It should be noted that patients addicted to cocaine show a considerable increase in κ receptors in the nucleus accumbens. This report describes the case of an abstinent cocaine-addicted patient regularly afflicted with cravings for cocaine. The patient took as-needed nalmefene for 5 months whenever she developed a craving for cocaine. For most of these interventions, the patient reported an abatement of craving and could avoid relapsing into cocaine consumption. This effect may be accounted for by nalmefene acting, other than naltrexone, as a partial agonist of the κ opioid-receptors. Therefore, nalmefene might be a promising new option in the pharmacological repertoire for the treatment of cocaine addiction.

Background: There are limited data on reasons for hospital admission among patients dependent on substances other than alcohol. We compared primary discharge diagnoses for heroin- or cocaine-dependent patients to non-dependent patients., Material and Methods: We evaluated a cohort of patients admitted to a general medicine service at a public teaching hospital during July 2005-June 2008. Through bedside interviews, we identified patients who had substance-use disorders. We categorized patients by substance used, route of administration, and dependent or non-dependent use. We grouped diagnostic codes (i.e., ICD-9) using Healthcare Utilization Project categories. We excluded HIV-infected patients., Results: Of 11,397 patients, 341 (3.0%) were dependent on inhalational heroin, 260 (2.3%) on non-injection cocaine, and 106 (0.9%) on injection heroin. Compared to non-dependent patients, inhalational heroin-dependent patients were over three-fold more likely to have been admitted for respiratory diseases (28% vs. 8%, p<0.01); this association was strongest for asthma exacerbation (OR=7.0; 95% CI, 4.7 to 70.4, p<0.01). Of the 225 admissions for an asthma exacerbation, 44 (19.6%) had co-occurrent heroin-dependence. The most frequent diagnostic category among cocaine-dependent patients was circulatory, which was similar to non-dependent patients (22% vs. 21%, p=0.92)., Discussion: There is a strong association between heroin dependence and hospital admission for an asthma exacerbation. Provision of specialized substance-use treatment for inhalational heroin users will be necessary to reduce the frequency of exacerbations and repeat hospital admissions.

Background: The urine of a patient admitted for chest and epigastric pain tested positive for cocaine using an immunoassay-based drug screening method (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial of recent cocaine use, this positive cocaine screening result in conjunction with a remote history of drug misuse impacted the patient's recommended pain therapy. Specifically, these factors prompted the clinical team to question the appropriateness of opioids and other potentially addictive therapeutics during the treatment of cancer pain from previously undetected advanced pancreatic carcinoma., Objective: After pain management and clinical pathology consultation, it was decided that the positive cocaine screening result should be confirmed by gas chromatography-mass spectrometry (GC-MS) testing., Results: This more sensitive and specific analytical technique revealed that both cocaine and its primary metabolite benzoylecgonine were undetectable (i.e., less than the assay detection limit of 50 ng/mL), thus indicating that the positive urine screening result was falsely positive. With this confirmation, the pain management service team was reassured in offering intrathecal pump (ITP) therapy for pain control. ITP implantation was well tolerated, and the patient eventually achieved excellent pain relief. However, ITP therapy most likely would not have been utilized without the GC-MS confirmation testing unless alternative options failed and extensive vigilant monitoring was initiated., Conclusion: As exemplified in this case, confirmatory drug testing should be performed on specimens with unexpected immunoassay-based drug screening results. To our knowledge, this is the first report of a false-positive urine cocaine screening result and its impact on patient management., (Wiley Periodicals, Inc.)

Cocaine dependence is a complex neuropsychiatric disorder manifested as dysregulation of multiple behavioral, emotional, and cognitive constructs. Neuroimaging studies have begun to identify specific neurobiological circuit impairments in cocaine-dependent (CD) individuals that may underlie these symptoms. However, whether, where, and how the interactions within and between these circuits are disrupted remain largely unknown. We used resting-state fMRI and modularity network analysis to identify brain modules of a priori interest (default-mode network [DMN], salience network [SN], executive control network [ECN], medial temporal lobe [MTL], and striatum) in 47 CD and 47 matched healthy control (HC) participants and explored alterations within and between these brain modules as a function of addiction. At the module level, intermodule connectivity decreased between DMN and SN in CD. At the nodal level, several regions showed decreased connections with multiple modules in CD: the rostral anterior cingulate connection strength was reduced with SN and MTL; the posterior cingulate had reduced connections with ECN; and the bilateral insula demonstrated decreased connections with DMN. Furthermore, alexithymia, a personality trait previously associated with addiction, correlated negatively with intramodule connectivity within SN only in cocaine users. Our results indicate that cocaine addiction is associated with disrupted interactions among DMN, MTL, and SN, which have been implicated, respectively, in self-referential functions, emotion and memory, and coordinating between internal and external stimuli, providing novel and important insights into the neurobiological mechanisms of cocaine addiction., (Copyright © 2015 the authors 0270-6474/15/358081-10$15.00/0.)

Background: Cocaine is a highly abused substance in United States with almost 70 % of cocaine adulterated with levamisole. It is known to cause vasculitis involving multiple organs due to its direct toxic effect and by the contribution of levamisole or a combined effect of both., Case Report: A 51-year-old woman complained of painful erythematous rash in her hands and lower extremities that started few hours after smoking cocaine and progressed to blistering dark lesions in her lower extremities. She denied any other systemic complaints. Although she has been smoking cocaine for more than 35 years, these skin eruptions started only 4 years ago. Examination revealed tender retiform purpura in the hand and tender retiform purpura with hemorrhagic bulla in the legs. Initially, she had only a significantly positive atypical p-ANCA and later developed combined positivity of both Myeloperoxidase (MPO) and Anti-proteinase-3(PR3) antibodies with a p-ANCA pattern on immunofluorescence. We report a unique case of cocaine (likely contaminated with levamisole)-induced delayed recurrent vasculitis with varying vasculitic antibodies over the years., Conclusions: This case highlights the fact that patients can develop cocaine-related vasculitis after many years of uneventful abuse. Cocaine, with its adulterant levamisole, has the propensity to trigger diverse immunological reactions, which is evident by the varying antibody profile seen in the same patient over time.

Rationale: Language production requires that speakers effectively recruit inhibitory control to successfully produce speech. The use of cocaine is associated with impairments in cognitive control processes in the non-verbal domain, but the impact of chronic and recreational use of cocaine on these processes during language production remains undetermined., Objectives: This study aims to observe the possible impairment of inhibitory control in language production among chronic and recreational cocaine polydrug users., Method: Two experiments were carried out on chronic (experiment 1) and recreational (experiment 2) cocaine polydrug users performing a blocked-cycled naming task, yielding an index of semantic interference. Participants were matched for sex, age, and intelligence (Raven's Standard Progressive Matrices) with cocaine-free controls, and their performance was compared on the blocked-cycled naming task., Results: Chronic and recreational users showed significantly larger semantic interference effects than cocaine-free controls, thereby indicating a deficit in the ability to inhibit interfering information., Conclusion: Evidence indicates a relationship between the consumption of cocaine, even at recreational levels, and the inhibitory processes that suppress the overactive lexical representations in the semantic context. This deficit may be critical in adapting and responding to many real-life situations where an efficient self-monitoring system is necessary for the prevention of errors.

Purpose: To explore whether reducing substance misuse through a brief motivational intervention also reduces aggression and HIV risk behaviours., Methods: Participants were enrolled in a randomized controlled trial in primary care if they screened positive for substance misuse. Substance misuse was assessed using the Alcohol, Smoking and Substance Involvement Screening Test; aggression, using a modified version of the Explicit Aggression Scale; and HIV risk, through a count of common risk behaviours. The intervention was received on the day of the baseline interview, with a 3-month follow-up., Results: Participants who received the intervention were significantly more likely to reduce their alcohol use than those who did not; no effect was identified for other substances. In addition, participants who reduced substance misuse (whether as an effect of the intervention or not) also reduced aggression but not HIV risk behaviours., Conclusions: Reducing substance misuse through any means reduces aggression; other interventions are needed for HIV risk reduction., (© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Rationale: Preclinical studies have shown that cocaine exposure and withdrawal are associated with cellular oxidative stress damage. However, the impact of crack-cocaine dependence on oxidative stress biomarkers remains unclear. Here, we assessed peripheral oxidative stress and antioxidant defences during two periods of crack-cocaine detoxification treatment and associated these changes with psychological morbidity., Methods: Thirty female inpatients were recruited, and plasma samples were collected at the 4th and 18th days of abstinence; 30 healthy controls were also recruited. Plasma levels of protein carbonyl, protein thiol content, superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced reduced (GSH) and total reactive antioxidant potential (TRAP) were measured by standard methods; the questionnaires Cocaine Selective Severity Assessment, Beck Depressive Inventory and the Addiction Severity Index were applied., Results: We report higher oxidative stress damage after 4 days of detoxification, as shown by increased total thiol content and protein carbonylation when compared with control group and after 18 days of detoxification. After 18 days of treatment, we observed a recovery of the oxidative stress damage and increase of the antioxidant defences, as shown by higher levels of SOD, GPx, GSH and TRAP. There was a positive correlation between protein carbonylation and psychological variables; in contrast, there was a negative correlation between TRAP levels and clinical assessments., Conclusions: Taken together, these results suggest that drug rehabilitation treatment was effective in decreasing oxidative damage represented by the reduction in biological markers, which are closely related to the severity of withdrawal symptoms.

Objective: To compare measures of sensation seeking in a clinical group of cocaine-dependent (CD) patients with and without a history of probable childhood ADHD and in non-cocaine-dependent (NCD) healthy volunteers., Method: Patients (n = 75; 42 with and 33 without probable childhood ADHD) and comparisons (n = 84) were assessed with the Diagnostic Interview for Genetic Studies, the Wender Utah Rating Scale for childhood ADHD, and the Zuckerman Seeking Sensation Scale., Results: We found significantly higher prevalence rates of probable childhood ADHD in CD versus NCD (p < .001). The mean total scores of sensation seeking were significantly higher in CD versus NCD participants (p < .001) as well as in CD patients with versus those without a probable history of childhood ADHD (p < .001)., Conclusion: Our study sets the basis for longitudinal investigation assessing whether the persistence of high level of sensation seeking in adults with childhood ADHD contributes to the transition to cocaine dependence., (© 2014 SAGE Publications.)

There are an estimated several million crack-cocaine users globally; use is highest in the Americas. Most crack users are socio-economically marginalized (e.g., homeless), and feature elevated risks for morbidity (e.g., blood-borne viruses), mortality and crime/violence involvement, resulting in extensive burdens. No comprehensive reviews of evidence-based prevention and/or treatment interventions specifically for crack use exist. We conducted a comprehensive narrative overview of English-language studies on the efficacy of secondary prevention and treatment interventions for crack (cocaine) abuse/dependence. Literature searches (1990-2014) using pertinent keywords were conducted in main scientific databases. Titles/abstracts were reviewed for relevance, and full studies were included in the review if involving a primary prevention/treatment intervention study comprising a substantive crack user sample. Intervention outcomes considered included drug use, health risks/status (e.g., HIV or sexual risks) and select social outcome indicators. Targeted (e.g., behavioral/community-based) prevention measures show mixed and short-term effects on crack use/HIV risk outcomes. Material (e.g., safer crack use kit distribution) interventions also document modest efficacy in risk reduction; empirical assessments of environmental (e.g., drug consumption facilities) for crack smokers are not available. Diverse psycho-social treatment (including contingency management) interventions for crack abuse/dependence show some positive but also limited/short-term efficacy, yet likely constitute best currently available treatment options. Ancillary treatments show little effects but are understudied. Despite ample studies, pharmaco-therapeutic/immunotherapy treatment agents have not produced convincing evidence; select agents may hold potential combined with personalized approaches and/or psycho-social strategies. No comprehensively effective 'gold-standard' prevention/treatment interventions for crack abuse exist; concerted research towards improved interventions is urgently needed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Recent studies have identified biomarkers related to the severity and pathogenesis of cocaine addiction and common comorbid psychiatric disorders. Monitoring these plasma mediators may improve the stratification of cocaine users seeking treatment. Because the neurotrophic factors are involved in neural plasticity, neurogenesis and neuronal survival, we have determined plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and IGF-1 binding protein 3 (IGFBP-3) in a cross-sectional study with abstinent cocaine users who sought outpatient treatment for cocaine (n = 100) and age/body mass matched controls (n = 85). Participants were assessed with the diagnostic interview 'Psychiatric Research Interview for Substance and Mental Disorders'. Plasma concentrations of these peptides were not different in cocaine users and controls. They were not associated with length of abstinence, duration of cocaine use or cocaine symptom severity. The pathological use of cocaine did not influence the association of IGF-1 with age observed in healthy subjects, but the correlation between IGF-1 and IGFBP-3 was not significantly detected. Correlation analyses were performed between these peptides and other molecules sensitive to addiction: BDNF concentrations were not associated with inflammatory mediators, lipid derivatives or IGF-1 in cocaine users, but correlated with chemokines (fractalkine/CX3CL1 and SDF-1/CXCL12) and N-acyl-ethanolamines (N-palmitoyl-, N-oleoyl-, N-arachidonoyl-, N-linoleoyl- and N-dihomo-γ-linolenoyl-ethanolamine) in controls; IGF-1 concentrations only showed association with IGFBP-3 concentrations in controls; and IGFBP-3 was only correlated with N-stearoyl-ethanolamine concentrations in cocaine users. Multiple substance use disorders and life-time comorbid psychopathologies were common in abstinent cocaine users. Interestingly, plasma BDNF concentrations were exclusively found to be decreased in users diagnosed with both primary and cocaine-induced disorders for mood and anxiety disorders. In summary, BDNF, IGF-1 and IGFBP-3 were not affected by a history of pathological use of cocaine supported by the absence of associations with other molecules sensitive to cocaine addiction. However, BDNF was affected by comorbid mood disorders. Further research is necessary to elucidate the role of BDNF and IGF-1 in the transition to cocaine addiction and associated psychiatric comorbidity.

Background: Experimental studies in animal models and case reports in humans have described the hepatotoxic potential of cocaine. However, there are few data regarding the clinical and laboratory characteristics of patients admitted for cocaine intoxication, particularly regarding the status of the liver enzymes., Goal: To investigate the significance of alanine aminotransferase (ALT) levels in individuals hospitalized for acute cocaine intoxication., Methods: Retrospective study with standardized chart review that included patients admitted between January 2003 and December 2010. Bivariate analyses were used to investigate factors associated with ALT above the upper tertile according to gender. Cases of marked ALT elevation were described in detail., Results: Ninety-three patients were included (79% men, mean age of 27.73±9.97 y). ALT above the upper tertile was associated with higher aspartate aminotransferase (AST), creatine phosphokinase, creatinine, and international normalized ratio. Higher levels of ALT were also related to acute renal failure and death. Five subjects had severe ALT elevation during follow-up and all had evidence of hepatocellular dysfunction (jaundice, prolonged prothrombin time with or without hepatic encephalopathy), rhabdomyolysis, and acute renal failure. AST/ALT ratio <2 was present in 2 subjects with severe ALT elevation at admission, but AST/ALT ratio >2 was observed in 3 cases with evidence of progression to acute liver injury., Conclusions: In acute cocaine intoxication, higher ALT levels were associated with evidence of muscle damage, progression to acute renal failure, and death. Severe liver damage was observed in 5% of the sample and was associated with rhabdomyolysis and renal failure in all cases.

Objective: To assess the effect of a positive urine screen for cocaine on thyrotropin (TSH, also thyroid-stimulating hormone) concentrations., Methods: In this retrospective cohort study, patients admitted to the mental health unit at an academic inpatient setting with a diagnosis of cocaine dependence or cocaine intoxication were routinely screened with urine drug toxicology tests and TSH concentrations. TSH concentrations from patients who tested positive for cocaine on urine toxicology were compared with patients having negative cocaine screenings., Results: A total of 192 patients were included: 122 with a positive cocaine screen and 70 with a negative cocaine screen. All patients were screened using a highly sensitive TSH assay. A positive cocaine screen was not associated with a statistically significant difference in TSH concentrations compared with a negative cocaine screen. The percentage of patients with hypothyroidism (TSH >4.50 μIU/mL) or hyperthyroidism (TSH <0.40 μIU/mL) were similar in both study groups., Conclusions: The study failed to show that a positive urine screen for cocaine was associated with a significant effect on serum TSH levels in patients admitted to a mental health unit with a diagnosis of cocaine dependence or cocaine intoxication. Our findings support those of a prior study that cocaine use does not affect routine thyroid function tests. The present study does not support the clinical practice of ordering a serum TSH screening test on patients admitted to inpatient psychiatry units soley because the urine screen is positive for cocaine.

Purpose: The purpose of this study was to estimate the reliability and provide evidence for the validity of the Spanish version of the Substance Dependence Severity Scale (SDSS)., Methods: A total of 211 substance abusers recruited at a public center that provides treatment for substance-related disorders in an outpatient setting were assessed. Reliability was estimated by Cronbach's α and test-retest. Validity evidence was studied by analyzing the relationships with the European Addiction Severity Index (EuropASI) and Health-Related Quality of Life for Drug Abusers (HRQoLDA)., Results: Adequate reliability coefficients were found for the dependence scales of all addressed substances (α = 0.737 to 0.877; test-retest r = 0.796-0.952). Low internal consistency was found for the abuse scales (α = 0.329-0.694), and adequate test-retest coefficients on alcohol, cocaine and heroin (test-retest r = 0.708-0.902). The reliability of the cannabis abuse scales was inadequate. The SDSS scores showed significant relationships with the EuropASI and HRQoLDA dimensions., Conclusions: The psychometric analyses validate the use of the severity of dependence scales. The SDSS abuse scales must be used taking the limitations detected into consideration.

Co-occurring cocaine use and posttraumatic stress disorders are prevalent and associated with negative treatment, health and societal consequences. This study examined the relationships among PTSD symptoms, gender, and cocaine use problems. Within a cross-sectional design, we gathered archival point prevalence data on new admissions (n = 573) to three addiction treatment agencies. Demographic, substance use, and PTSD symptom information were collected across the three agencies. Logistic regression analyses revealed that patients with cocaine use disorders had a two-fold increased odds for a probable PTSD diagnosis, compared to patients without a cocaine use disorder (OR = 2.19, 95% CI = 1.49-3.22, p < 0.001). Among females with cocaine use disorder, multinomial regression yielded a significant increase in the risk of moderate (RRR = 2.12, 95% CI = 1.10-4.10, p < 0.05) and severe (RRR = 2.87, 95% CI = 1.33-6.21, p < 0.01) PTSD symptoms. Males with cocaine use disorders had a two-fold increase in the risk of moderate PTSD symptoms (RRR = 2.13, 95% CI = 1.23-3.68, p < 0.01), but had no increased risk of developing severe PTSD symptoms (RRR = 1.93, 95% CI = 0.85-4.39, p = 0.117). Cocaine use appears to impact the risk of PTSD symptoms, especially in females. Future research should explore the generalizability of these findings to more racially and ethnically diverse samples, as well as among persons with this comorbidity who are not engaged in treatment services.

Contrary to the illegal use of any form of manufactured cocaine, chewing of coca leaves and drinking of coca tea are allowed and are very common and socially integrated in several South American countries. Because of this different legal state, an analytical method for discrimination between use of coca leaves and abuse of processed cocaine preparations is required. In this study, the applicability of hair analysis for this purpose was examined. Hair samples from 26 Argentinean coca chewers and 22 German cocaine users were analysed for cocaine (COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), cuscohygrine (CUS) and hygrine (HYG) by hydrophilic interaction liquid chromatography (HILIC) in combination with triplequad mass spectrometry (MS/MS) and hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS). The following concentrations (range, median, ng/mg) were determined in hair of the coca chewers: COC 0.085-75.5, 17.0; NC 0.03-1.15, 0.12; BE 0.046-35.5, 6.1; EME 0.014-6.0, 0.66; CE 0.00-13.8, 0.38; CIN 0.005-16.8, 0.79; TRO 0.02-0.16, 0.023; CUS 0.026-26.7, 0.31. In lack of a reference substance, only qualitative data were obtained for HYG, and two metabolites of CUS were detected which were not found in hair of the cocaine users. For interpretation, the concentrations of the metabolites and of the coca alkaloids in relation to cocaine were statistically compared between coca chewers and cocaine users. By analysis of variance (ANOVA) significant differences were found for all analytes (α = 0.000 to 0.030) with the exception of TRO (α = 0.218). The ratios CUS/COC, CIN/COC and EME/COC appeared to be the most suitable criteria for discrimination between both groups with the means and medians 5-fold to 10-fold higher for coca chewers and a low overlap of the ranges between both groups. The same was qualitatively found for HYG. However, these criteria cannot exclude cocaine use in addition to coca chewing. In this regard screening for typical cutting agents can be helpful and led to the detection of levamisole (21×), lidocaine (6×) and paracetamol (3×) in the 22 samples from German cocaine users, whereas no levamisole, lidocaine (3×) and paracetamol (1×) were found in hair from the Argentinean coca chewers. These criteria have to be confirmed for South American cocaine consumers including smokers of coca paste and may be different because of different composition of the drug and other use habits.

Background: The Obsessive Compulsive Drug Use Scale (OCDUS) and the Desires for Drug Questionnaire (DDQ) are two frequently used drug craving questionnaires. Although both heroin and cocaine versions of the questionnaires exist, only the heroin versions have been psychometrically evaluated. The present study was conducted to evaluate the psychometric qualities of the cocaine versions of the OCDUS (OCDUS-C) and DDQ (DDQ-C)., Methods: Cocaine-dependent inpatients (n = 101) completed both scales as well as a Visual Analogue Craving Scale (VACS), an alternative, one-item index for assessing momentary craving. We examined the reliability (internal consistency), construct validity (factor structure), and concurrent validity (correlations among both questionnaires, the VACS, and indicators of severity of dependence). A subsample also completed the OCDUS-C and DDQ-C for a second time, one week after the initial administration to obtain a preliminary investigation of the test-retest reliability., Results: In general, both questionnaires displayed good internal consistency, test-retest reliability, and concurrent validity. Further, the construct validity of both the DDQ and OCDUS was demonstrated by means of confirmatory factor analyses showing the expected three-factor models., Conclusion: Our results indicate that the OCDUS and DDQ for cocaine are both easy to administer and reliable instruments to assist the clinical practitioner or researcher to measure craving in cocaine dependent subjects. Moreover, the factor structure for the cocaine versions were similar to the heroin versions, indicating the OCDUS and the DDQ can be reliably used to measure craving for both substances, enabling a direct comparison between heroin and cocaine craving.

Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient.

Cocaine use continues to be a major public health problem in the United States. Although many of the initial signs and symptoms of cocaine intoxication result from increased stimulation of the sympathetic nervous system, this condition can present as a spectrum of acuity from hypertension and tachycardia to multiorgan system failure. Classic features of acute intoxication include tachycardia, arterial vasoconstriction, enhanced thrombus formation, mydriasis, psychomotor agitation, and altered level of consciousness. At the extreme end of this toxidrome is a rare condition known as cocaine-induced agitated delirium. This syndrome is characterized by severe cardiopulmonary dysfunction, hyperthermia, and acute neurologic changes frequently leading to death. We report a case of cocaine-induced agitated delirium in a man who presented to our institution in a paradoxical form of circulatory shock. Rapid evaluation, recognition, and proper management enabled our patient not only to survive but also to leave the hospital without neurologic sequelae., (© The Author(s) 2013.)

Background: The Heidelberger Drogenbogen (HDB) is a German language assessment of substance-specific knowledge and consumption patterns of the illicit psychoactive substances cannabis, MDMA (ecstasy), amphetamines, cocaine, and hallucinogens. The behavior modules for each of these five drugs/drug groups allow for a diagnostic evaluation of the extent of harmful consumption behavior. Each of the five modules represents a single standardized test., Objectives: This paper outlines several statistical parameters, Cronbach's alpha, retest reliabilities, as well as numerous validity and cut-off-criteria of the behavioral modules., Methods: Participants (N = 4,794) were recruited at schools, universities, in subcultural contexts, and in institutions of substance abuse treatment., Results: Internal consistencies range from = .68 to .79 while test-retest reliabilities between .87 and .94 were found. The behavior modules of the HDB can discriminate between populations with and without clinical levels of substance use. Furthermore, this measure has incremental validity and higher diagnostic accuracy over competing measures., Conclusions: The behavior modules of the HDB are reliable and valid measures of substance use and misuse.

Cocaine use is still a problem in today's world, and this has several implications on human activities. Indeed, important problems related to cocaine derive from its use in situations where concentration and focus skills are necessary, namely while driving and/or working. The need of analytical methods for drug analysis in specimens of biological origin for proper documentation of human exposure is increasing. While GC-MS-based procedures represented the state-of-the-art of analytical techniques a few years ago, there is a growing trend for their replacement by LC-MS/MS, which can be justified by the increased sensitivity presented by these new technologies. This paper will review recently published papers on the use of LC-MS/MS-based procedures for cocaine measurement in biological specimens.

Background: Cocaine has become one of the drugs of most concern in Switzerland, being associated with a wide range of medical, psychiatric and social problems. Available treatment options for cocaine dependence are rare. The study sought to compare combined prize-based contingency management (prizeCM) plus cognitive-behavioral therapy (CBT) to CBT alone in cocaine-dependent patients., Methods: Sixty cocaine-dependent patients participated in a randomized, controlled trial with two treatment conditions. The participants were randomly assigned to the experimental group (EG; n = 29), who received CBT combined with prizeCM, or to the control group (CG; n = 31), who received CBT only during 24 weeks. The primary outcome measures were retention, at least 3 consecutive weeks of cocaine abstinence, the maximum number of consecutive weeks of abstinence and proportions of cocaine-free urine samples during the entire 24-week and at 6-month follow-up., Results: Sixty-three percent of the participants completed the study protocol. Participants in both groups significantly reduced cocaine use over time. Overall, no difference in cocaine-free urine screens was found across the two treatment groups, except at weeks 8, 9, 10, 17 and 21 in favor of the EG., Conclusions: The addition of prizeCM to CBT seems to enhance treatment effects, especially in the early treatment period, supporting results from previous studies. Both the combined intervention and CBT alone, led to significant reductions in cocaine use during treatment and these effects were sustained at 6-month follow-up. These findings underline the importance in implementing CM and CBT interventions as treatment options for cocaine dependence in the European context., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Introduction: The autobiographical Implicit Association Test (aIAT) is a variant of the Implicit Association Test reportedly capable of detecting an individual's concealed autobiographical event with very high accuracy. A previous attempt to utilize this measurement technique for the identification of cocaine users rendered an alarming rate of false positives. In this study, we aimed to explore the potential reasons behind the measurement's inaccuracy., Methods: Two versions of the cocaine aIAT were devised with different category labels (descriptive 'guilty/innocent' and self-referenced 'as if you were/were not'). Forty-one cocaine abstinent participants (43.9% male; mean age = 28.17 ± 7.36) were randomly assigned to one of the two conditions. Self-declared cocaine abstinence was confirmed for the 12-month period preceding data collection through hair analysis. Participants were also administered bespoke implicit and explicit cocaine user attitude measures, the self-esteem IAT and the Rosenberg self-esteem scale., Results: The category labels which elicited self-referenced knowledge showed low accuracy (19%) compared to the 65% of the 'guilty/innocent' labels proposed by original authors. The self-referenced aIAT version significantly correlated with the self-concept measures. The aIAT outcomes were independent from attitudes toward cocaine users., Conclusions: Category labels play an influential role in determining the test's accuracy, demonstrating that participants' propositional knowledge and self-concept are involved during test performance. The aIAT does not appear to tap directly into an individual's implicit memory when relevant memory is not available. Although the test cannot be recommended for detecting drug use, further research should investigate underlying mechanisms and other potentials of the technique., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Substance abuse is a risk factor for HIV infection and progression to AIDS. Recent evidence establishes that cocaine use promotes brain perivascular macrophage infiltration and microglia activation. The lysosomal protease cathepsin B is increased in monocytes from patients with HIV dementia and its secretion induces 10-15% of neurotoxicity. Here we asked if cocaine potentiates cathepsin B secretion from HIV-infected monocyte-derived macrophages (MDM) and its effect in neuronal apoptosis. Samples of plasma, CSF, and post-mortem brain tissue from HIV positive patients that used cocaine were tested for cathepsin B and its inhibitors to determine the in vivo relevance of these findings. MDM were inoculated with HIV-1ADA, exposed to cocaine, and the levels of secreted and bioactive cathepsin B and its inhibitors were measured at different time-points. Cathepsin B expression (p < 0.001) and activity (p < 0.05) increased in supernatants from HIV-infected cocaine treated MDM compared with HIV-infected cocaine negative controls. Increased levels of cystatin B expression was also found in supernatants from HIV-cocaine treated MDM (p < 0.05). A significant increase in 30% of apoptotic neurons was obtained that decreased to 5% with the specific cathepsin B inhibitor (CA-074) or with cathepsin B antibody. Cathepsin B was significantly increased in the plasma and post-mortem brain tissue of HIV/cocaine users over non-drug users. Our results demonstrated that cocaine potentiates cathepsin B secretion in HIV-infected MDM and increase neuronal apoptosis. These findings provide new evidence that cocaine synergize with HIV-1 infection in increasing cathepsin B secretion and neurotoxicity.

Background: Individuals with gambling or substance-use disorders exhibit similar functional alterations in reward circuitry suggestive of a shared underlying vulnerability in addictive disorders. Additional research into common and unique alterations in reward-processing in substance-related and non-substance-related addictions may identify neural factors that could be targeted in treatment development for these disorders., Methods: To investigate contextual reward-processing in pathological gambling, a slot-machine fMRI task was performed by three groups (with pathological gambling, cocaine dependence and neither disorder; N = 24 each) to determine the extent to which two groups with addictions (non-substance-related and substance-related) showed similarities and differences with respect to each other and a non-addicted group during anticipatory periods and following the delivery of winning, losing and 'near-miss' outcomes., Results: Individuals with pathological gambling or cocaine dependence compared to those with neither disorder exhibited exaggerated anticipatory activity in mesolimbic and ventrocortical regions, with pathological-gambling participants displaying greater positive possible-reward anticipation and cocaine-dependent participants displaying more negative certain-loss anticipation. Neither clinical sample exhibited medial frontal or striatal responses that were observed following near-miss outcomes in healthy comparison participants., Conclusions: Alterations in anticipatory processing may be sensitive to the valence of rewards and content-disorder-specific. Common and unique findings in pathological gambling and cocaine dependence with respect to anticipatory reward and near-miss loss processing suggest shared and unique elements that might be targeted through behavioral or pharmacological interventions in the treatment of addictions., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Despite extensive research on gender differences in addiction, there are relatively few published reports comparing treatment outcomes for women versus men based on evidence-based treatments evaluated in randomized clinical trials., Methods: An aggregate sample comprised of data from five randomized clinical trials of treatment for cocaine dependence (N = 434) was evaluated for gender differences in clinical outcomes. Secondary analyses compared gender differences in outcome by medication condition (disulfiram versus no medication) and across multiple behavioral treatment conditions., Results: Women, compared with men, had poorer treatment outcomes on multiple measures of cocaine use during treatment and at post-treatment follow-up. These results appear to be primarily accounted for by disulfiram being less effective in women compared with men. There was no evidence of meaningful gender differences in outcome as a function of the behavioral therapies evaluated., Conclusions: These findings suggest that women and men may benefit to similar degrees from some empirically validated behavioral treatments for addiction. Conversely, some addiction pharmacotherapies, such as disulfiram, may be associated with poorer outcomes among women relative to men and point to the need for careful assessment of pharmacological treatments in both sexes prior to widespread clinical implementation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Because levamisole has been increasingly found as a component of illicit drugs, a robust method to detect its presence in hair samples is needed. However, no systematic research on the detection of levamisole in hair samples has been published. The method presented here uses direct immersion solid-phase microextraction coupled with gas chromatography and mass spectrometry (DI-SPME-GC/MS) to detect levamisole and minor cocaine congeners in hair samples using a single-extraction method., Methods: Fifty hair samples taken in the last 4 years were obtained from cocaine abusers, along with controls taken from drug-free volunteers. Sampling was performed using direct immersion with a 30-μm polydimethylsiloxane fused silica/stainless steel fiber. Calibration curves were prepared by adding known amounts of analytes and deuterated internal standards to the hair samples taken from drug-free volunteers. This study focused on the adulterant levamisole and some minor cocaine congeners (tropococaine, norcocaine, and cocaethylene)., Results: Levamisole was detected in 38% of the hair samples analyzed; its concentration ranged from 0.2 to 0.8 ng/mg. The limit of quantification and limit of detection for levamisole, tropococaine, norcocaine, and cocaine were 0.2 and 0.1 ng/mg, respectively., Conclusions: DI-SPME-GC/MS is a sensitive and specific method to detect the presence of levamisole and cocaine congeners in hair samples.