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Neutrophilic dermatoses encompass a wide spectrum of diseases characterized by a dense infiltration mainly composed of neutrophils. Neutrophilic dermatosis of the dorsal hands is currently considered a localized variant of Sweet syndrome. Cocaine abuse has been related to a wide range of mucocutaneous manifestations, including neutrophilic dermatoses such as pyoderma gangrenosum. The authors of this study present a patient with neutrophilic dermatosis of the dorsal hands, in which cocaine abuse was identified as a probable trigger.

Caso relatado na Reunião de Discussão de Casos Clínicos do Hospital Universitário Prof. Polydoro Ernani de São Thiago, iniciada pelos Profs. Jorge Dias de Matos, Marisa Helena César Coral e Rosemeri Maurici da Silva, em julho de 2017. No dia 13 de junho de 2019, no bloco do curso de medicina, realizou-se a apresentação e discussão do caso cujo registro é apresentado a seguir: um paciente de 38 anos é acompanhado no ambulatório de reumatologia, com uma doença destrutiva das vias aéreas superiores, pansinusopatia, ANCA e anti-proteinase 3 positivos. É usuário crônico de cocaína inalável e de corticosteróides. Um dia, dá entrada na emergência com cefaleia aguda e meningismo. Qual é o diagnóstico?Case reported at the Clinical Cases Discussion Meeting of the University Hospital “Polydoro Ernani of São Thiago”, initiated by Profs. Jorge Dias de Matos, Marisa Helena César Coral and Rosemeri Maurici da Silva, July 2017. On June 13, 2019, in the medical school block, the case was presented and discussed: A 38-year-old male patient is followed at the rheumatology outpatient clinic with a destructive upper airway disease, pansinusopathy, positive ANCA and anti-proteinase 3. He is a chronic user of inhaled cocaine and corticosteroids. One day, he comes to the emergency room with acute headache and meningism. What is the diagnosis?

Introduction Brazil is the world’s biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. Method We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil’s largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. Results Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). Conclusion Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants. Resumo Introdução O Brasil é o maior consumidor mundial de crack, e a dependência é um grande problema de saúde pública. Este é o primeiro estudo a investigar a prevalência de adulterantes potencialmente nocivos presentes em amostras de cabelo de pacientes brasileiros com dependência de crack. Métodos Foram avaliados adulterantes em amostras de cabelos extraídos por conveniência de 100 pacientes internados na unidade de observação de 48 horas do Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), o maior centro de tratamento de dependência do Brasil. Uma análise transversal foi realizada com os dados obtidos. Resultados Foram encontrados adulterantes em 97% das amostras de cabelo analisadas. O adulterante mais prevalente foi a lidocaína (92%), seguida da fenacetina (69%) e levamisol (31%). Conclusão Os adulterantes foram amplamente prevalentes em amostras de cabelo de usuários de crack tratados no CRATOD: pelo menos um adulterante estava presente em praticamente todas as amostras de cabelo coletadas. Isso aponta para a necessidade de monitorar os efeitos adversos no ambiente clínico, a fim de proporcionar a esse grupo de pacientes de alto risco cuidados imediatos e efetivos relacionados às complicações agudas e crônicas associadas a esses adulterantes.

Risky decision-making is characteristic of drug users, but little is known about the effects of circumstances, such as abstinence, on risky choice behavior in human drug users. We hypothesized that cocaine users would make more risky choices for cocaine (defined as taking a chance to receive a large number of cocaine doses as opposed to choosing to receive a fixed amount of cocaine) after 3 or 7 days of cocaine abstinence, compared to 1 day of cocaine abstinence. Six male nontreatment-seeking current cocaine smokers were enrolled in a 21-day inpatient within-subject study. Participants repeatedly smoked six 25 mg doses of cocaine during a training session and were instructed that they would be making decisions about smoking this dose throughout the study. After 1, 3 and 7 days of cocaine abstinence, participants completed a computerized task in which they repeatedly decided between receiving a guaranteed number of cocaine doses (between 1 and 5; fixed option) or receiving a chance (0.13 to 0.75) to smoke a larger number of cocaine doses (probabilistic option). After completing the computerized task, one of the participants' choices was randomly implemented and they smoked either the fixed number of cocaine doses or had the specified chance to smoke the greater number of doses. Contrary to our hypothesis, 5 of the 6 participants made fewer risky choices after 3 and 7 days of cocaine abstinence compared to one day of abstinence suggesting greater risk-aversion. Thus, even during cocaine abstinence cocaine users make rational decisions related to their drug use.

In July 2020, the Massachusetts Drug Supply Data Stream (MADDS) encountered two drug samples sold in a community as cocaine (one as “crack” and one as “white rock”) that contained bupropion as the ...

Mucocutaneous leishmaniasis (MCL) is a chronic infection that can affect the skin and mucous membranes. We report a case of oral, nasopharyngeal, and penile lesions in a 35-year-old cocaine user. The patient presented with ulcerated lesions in 2014. Histopathologic analysis revealed amastigotes, and serological test results were positive for leishmaniasis. Systemic therapy with meglumine antimoniate was administered; however, the patient failed to present for follow-up. In 2018, he returned with nasal collapse, and another histopathologic test confirmed MCL. This case illustrates the importance of careful differential diagnosis of skin and mucous ulcers to identify the particular pathology.

Levamisole is a veterinary antihelminthic, chemotherapeutic agent, and immunomodulator that also is used as an adulterant and cutting agent in cocaine distribution. This drug may potentiate the sympathomimetic actions of cocaine and can cause neutropenia, agranulocytosis, purpuric retiform lesions, and skin necrosis. This article describes two cases of suspected levamisole-induced vasculitis. No standardized diagnostic or treatment algorithm exists for this challenging condition. Diagnosis and treatment require a multidisciplinary team approach.

The infralimbic prefrontal cortex serves complex roles in controlling drug-seeking behavior. In this issue of Neuron, Cameron et al. (2019) provide new insights into engagement and function of the infralimbic cortex → nucleus accumbens corticostriatal pathway in the incubation of cocaine craving.

To the EditorWe appreciate the comments of Megarbane et al. regarding our previous article published in CLINICAL TOXICOLOGY [1]. They add interesting data on patients with cocaine intoxication that...

Resumo A Política de Atenção Integral ao Usuário de Drogas determina que as práticas de cuidado abranjam as dimensões biopsicossociais. Evidências, entretanto, revelam uma prática institucionalizante, na qual as famílias priorizam o afastamento do sujeito de seu contexto de uso. Este estudo objetivou compreender as implicações da atenção psicossocial e da institucionalização no atendimento às necessidades de adolescentes em situação de uso de crack e de seus familiares. Onze adolescentes e seis familiares narraram suas experiências, por meio de entrevistas em profundidade, as quais foram analisadas à luz da Hermenêutica Fenomenológica, de Paul Ricoeur. Observou-se um fluxo, no qual os adolescentes, na busca pelo cuidado, inicialmente, são institucionalizados para, em seguida, serem encaminhados aos serviços substitutivos. Urge, portanto, a necessidade do fortalecimento da rede de atenção psicossocial para que o cuidado ao adolescente usuário de crack seja ofertado de forma integral, garantindo o respeito aos direitos fundamentais dos adolescentes, como o direito à liberdade e à convivência familiar e comunitária. Abstract The Drug User Comprehensive Care Policy establishes that care practices should cover biopsychosocial realms. However, evidence reveals an institutionalized practice, in which families prioritize the subject’s seclusion from its context of use. This study aimed to understand the implications of psychosocial care and institutionalization in meeting the needs of adolescent crack users and their families. Eleven teenagers and six relatives narrated their experiences through in-depth interviews, which were analyzed in the light of Paul Ricoeur’s Phenomenological Hermeneutics. A flow was observed in which teenagers seeking care are initially institutionalized and then referred to replacement services. Thus, there is an urgent need to strengthen the psychosocial care network so that adolescent crack users’ care is offered comprehensively, ensuring respect for their fundamental rights, such as the right to freedom and to experience family or community life.

Manipulations of memory reconsolidation can interfere with the ability of a drug-paired cue to drive drug-seeking behavior. However, the typical reconsolidation paradigm that reactivates the memory through the presentation of the cue (conditioned stimulus (CS)) only interferes with the memory of the reactivated CS while leaving other drug-paired CSs intact and able to continue driving drug-seeking behavior. Here, we used a novel unconditioned-stimulus (US) reactivation paradigm to interfere with the ability of multiple cues to drive drug-seeking behavior after just one reactivation and treatment session. Rats were trained to self-administer cocaine, during which time each active lever press resulted in an i.v. cocaine infusion paired with one of two cues that alternated within each session. The drug memory was later reactivated with either i.v. or i.p. cocaine presentation in the absence of any cue. The histone acetyltransferase (HAT) inhibitor garcinol or vehicle was injected following US reactivation to impair reconsolidation. Rats were later tested on cue-induced reinstatement to both cues. Garcinol administered after either i.v. or i.p. cocaine reactivation significantly decreased cue-induced reinstatement to both cues, indicative of reconsolidation impairment. In addition, garcinol administered in the absence of reconsolidation or at a 6 h delay when the memory should be restabilized had no effect on reinstatement, further suggesting that garcinol’s effects on reinstatement are through reconsolidation-based mechanisms. Our results demonstrate that a US-reactivation paradigm may be preferable to traditional CS-reactivation paradigms for treating disorders that involve multiple CS–US associations and support investigations of garcinol as a therapeutic pharmacological agent.

Mucocutaneous leishmaniasis (MCL) is a chronic infection that can affect the skin and mucous membranes. We report a case of oral, nasopharyngeal, and penile lesions in a 35-year-old cocaine user. The patient presented with ulcerated lesions in 2014. Histopathologic analysis revealed amastigotes, and serological test results were positive for leishmaniasis. Systemic therapy with meglumine antimoniate was administered; however, the patient failed to present for follow-up. In 2018, he returned with nasal collapse, and another histopathologic test confirmed MCL. This case illustrates the importance of careful differential diagnosis of skin and mucous ulcers to identify the particular pathology.

Activation of corticotropin-releasing factor type 1 receptors (CRF-R1) in the ventral tegmental area (VTA) represents a critical mechanism for social defeat to escalate cocaine self-administration in adult rats.We determined the acute effect of a CRF-R1 antagonist (CP376395) microinfusion into the VTA prior to each episode of social defeat in adolescent rats and determined whether this drug treatment could prevent later escalation of cocaine taking in early adulthood.Rats were implanted with bilateral cannulae aimed at the VTA 5 days before the first social defeat. Bilateral microinfusion of CP376395 (500 ng/side) or vehicle occurred 20 min before each episode of social defeat on postnatal days (P) 35, 38, 41, and 44. Behavior was quantified on P35 and P44. On P57, rats were implanted with intra-jugular catheters, and subsequent cocaine self-administration was analyzed.CP376395-treated adolescent rats walked less and were attacked more slowly but were socially investigated more than vehicle-treated adolescents. Vehicle-treated rats showed increased social and decreased non-social exploration from P35 to P44, while CP376395-treated rats did not. Socially defeated, vehicle-treated adolescents took more cocaine during a 24-h unlimited access binge during adulthood. The latency to supine posture on P44 was inversely correlated with later cocaine self-administration during fixed and progressive ratio schedules of reinforcement and during the binge.CP376395 treatment in adolescence blocked escalation of cocaine taking in adulthood. Episodes of social defeat stress engender neuroadaptation in CRF-R1s in the VTA that alter coping with social stress and that persist into adulthood.

Background Despite the multitude of public health and community harms associated with crack cocaine use, little is known about factors associated with smoking crack in public and related risks such as rushed public crack smoking. Methods Data were derived from two prospective cohort studies of people who use illicit drugs in Vancouver, Canada between 2010 and 2014. Multivariable generalized estimating equations were used to identify the prevalence and correlates of public crack smoking and rushed public crack smoking. Results In total, 1085 participants who had smoked crack in the prior six months were eligible for the analysis, of which 379 (34.9 %) reported always or usually smoking crack in public in the previous six months at some point during the study period. Factors positively and independently associated with public crack smoking included public injection drug use (adjusted odds ratio [AOR]: 5.42, 95 % confidence interval [CI]: 3.76-7.82), homelessness (AOR: 3.48, 95 % CI: 2.77-4.36), at least daily crack use (AOR: 2.69, 95 % CI: 2.19-3.31), crack pipe sharing (AOR: 1.98, 95 % CI: 1.60-2.46), drug dealing (AOR: 1.59, 95 % CI: 1.30-1.94), recent incarceration (AOR: 1.47, 95 % CI: 1.09-1.98), noticing police presence when buying or using drugs (AOR: 1.30, 95 % CI: 1.06-1.60), and younger age (AOR: 1.03, 95 % CI: 1.01-1.04). Rushed public crack smoking, which was reported by 216 (28.8 %) of 751 participants who had smoked crack in public at least once during the study period, was positively and independently associated with homelessness (AOR: 2.61, 95 % CI: 1.96-3.49), at least daily crack use (AOR: 1.48, 95 % CI: 1.11-1.98), crack pipe sharing (AOR: 1.44, 95 % CI: 1.10-1.89), drug dealing (AOR: 1.39, 95 % CI: 1.04-1.86), and younger age (AOR: 1.02, 95 % CI: 1.01-1.04). Conclusions A high prevalence of public crack smoking and rushed public crack smoking was observed in this setting. These findings point to the need for implementing and evaluating evidence-based public health interventions, such as supervised inhalation facilities, to reduce the risks and harms associated with smoking crack in public.

Attentional bias (i.e., differences in reaction time between drug and neutral cues) has been associated with a variety of drug-use behaviors (e.g., craving, abstinence). Reduction of bias may ultimately reduce use.The current study examined whether attentional bias modification therapy (ABMT) reduced the frequency of drug use behaviors in individuals with cocaine use disorder (CUD).Participants (n = 37) were randomly assigned to ABMT or control therapy, which systematically varied how frequently probes replaced neutral (ABMT = 100%; control therapy = 50%) relative to drug stimuli. Each intervention included 5 training sessions comprising a total of 2640 trials over 4 weeks. Clinical assessments occurred at baseline, post-intervention, 2 weeks and 3 months posttreatment.There were no baseline differences between groups on drug-use behaviors or other clinical measures. Contrary to predictions, both groups exhibited slower rather than faster reaction times for cocaine stimuli (p = 0.005) at baseline, with no relationship between bias and baseline measures of drug-use behavior.ABMT was not more effective than our control therapy at reducing attentional bias, reducing craving or changing other drug use behaviors. Current results suggest additional replication studies are needed to assess ABMT's efficacy in reducing drug-use behaviors in CUD.

Hygrine (HYG) and cuscohygrine (CUS) are natural alkaloids of coca leaves but are not found in illicit cocaine seizures. Therefore, they were proposed as markers for coca chewing in contrast to cocaine abuse in urine and hair testing. In order to examine at which step of the illegal cocaine production these compounds are lost, coca leaves were processed according to an authentic procedure by extraction with lime and kerosene, re-extraction with sulphuric acid, and precipitation of coca paste with ammonia. Non-extracted and extracted coca leaves, acidic extract and coca paste were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for cocaine, ecgonine methyl ester (EME), cinnamoylcocaine (CIN), HYG, and CUS. It follows from the results that under these conditions, HYG and CUS are extracted only to a minor extent by kerosene and are not precipitated from the acidic re-extract in the coca paste. Due to this behaviour in illegal cocaine production, they fulfil the conditions as markers for coca chewing in an optimal way. However, for unambiguous discrimination between coca chewing and cocaine abuse in human samples, additional markers of manufactured cocaine are required. Copyright © 2016 John Wiley & Sons, Ltd.

We previously demonstrated that nELAV/GAP-43 pathway is pivotal for learning and its hippocampal expression is up-regulated by acute stress following repeated cocaine administration. We therefore hypothesized that abstinence-induced stress may sustain nELAV/GAP-43 pathway during early abstinence following 2 weeks of cocaine self-administration. We found that contingent, but not non-contingent, cocaine exposure selectively increases hippocampal nELAV, but not GAP-43, expression immediately after the last self-administration session, an effect that wanes after 24 h and that comes back 7 days later when nELAV activation becomes associated with increased expression of GAP-43, an effect again observed only in animals self-administering the psychostimulant. Such effect is specific for nELAV since the ubiquitous ELAV/HuR is unchanged. This nELAV profile suggests that its initial transient alteration is perhaps related to the daily administration of cocaine, while the increase in the nELAV/GAP-43 pathway following a week of abstinence may reflect the activation of this cascade as a target of stressful conditions associated with drug-related memories. © 2016 Wiley Periodicals, Inc.

Comorbid neuropsychiatric disorders such as addiction and anxiety could involve common underlying mechanisms. One potential mechanism involves epigenetic regulation of histone 3 dimethylation at lysine 9 residues (H3K9me2) by the histone dimethyltransferase G9a. Here we provide evidence that local AAV-RNAi-mediated knockdown of G9a expression in nucleus accumbens shell (NAcSh) of male rats reduces both addictive-related and anxiety-related behaviors. Specifically, G9a knockdown reduces sensitivity to low dose cocaine reinforcement when cocaine is freely available (fixed ratio schedule). Similarly, G9a knockdown reduces motivation for cocaine under higher effort demands (progressive ratio schedule). Following several weeks of forced abstinence, G9a knockdown attenuates extinction responding and reinstatement triggered by either cocaine-priming injections or footshock stress. This decrease in addictive behavior is associated with a long-term reduction in anxiety-like behavior as measured by the elevated plus maze (EPM). G9a knockdown also reduces basal anxiety-like behavior in EPM and marble burying tests in drug-naïve rats. These results complement our previous work showing that increased G9a expression in NAcSh enhances addictive-related and anxiety-related behaviors, indicating that G9a bi-directionally controls these responses. These results also suggest that regulation of G9a-influenced gene expression could be a common epigenetic mechanism for co-morbid anxiety and psychostimulant addiction.

This corrigendum corrects article “Yellow and black-stained fingers in a patient with headache” and its publication references ie The Pan African Medical Journal. 2017;28:318. doi:10.11604/pamj.2017.28.318.14333.

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.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).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.These findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure.

In einer Online-Studie wurden mogliche Unterschiede zwischen drei Typen von Konsumenten (NichtkonsumentInnen, Freizeit-User, Gruppe mit riskantem Konsum) psychotroper Substanzen hinsichtlich der Emotionsregulation, der gesundheitsbezogenen Lebensqualitat sowie der Copingstrategien untersucht. Insgesamt nahmen 199 Personen teil. Die Stichprobe konnte mithilfe einer Substanzliste und eines detaillierten Fragenkatalogs (Konsumverhalten) in drei Gruppen geteilt werden: NichtkonsumentInnen (n = 28), Freizeit-User (n = 127), riskante KonsumentInnen (n = 44). Eingesetzt wurde unter anderem das Emotionsregulationsinventar, das Coping Inventory for Stressful Situations und der MOS Short-Form 36 Health. In der Emotionsregulation (ER) konnte in der Skala Umbewertung ein signifikanter Unterschied beobachtet werden; hierbei zeigte die Gruppe mit riskantem Konsum hohere Auspragungen als die Gruppe der Freizeit-User. Des Weiteren unterschieden sich die Konsumgruppen nicht signifikant in der gesundheitsbezogenen Lebensqualitat („health related quality of life“, HRQOL). Es gab einen signifikanten Unterschied zwischen Personen mit guter und schlechter korperlicher bzw. mentaler HRQOL hinsichtlich ihrer Zufriedenheit mit der eigenen Emotionsregulation. Die Pradiktorensuche ergab, dass das Geschlecht, die Einwohnerzahl des Wohnorts und die ER-Strategie Umbewertung bei negativen Emotionen einen signifikanten Vorhersagewert fur die Gruppenzugehorigkeit haben. Demnach konnte Substanzkonsum weder als ER-Strategie noch im Zusammenhang mit Copingstrategie oder gesundheitsbezogener Lebensqualitat beobachtet werden. Hinsichtlich der ER zeigte sich ein signifikantes Ergebnis. Hier verwendeten die Personen mit riskantem Konsumverhalten ofter die vermeintlich „gesunde“ Strategie der Umbewertung als die Freizeit-User. Eine Erklarung dafur konnte sein, dass diese Strategie im Zusammenhang mit Drogenkonsum eine realitatsverschonernde bzw. verharmlosende Funktion besitzt. Demnach konnte der postulierte Zusammenhang zwischen affektiver Dysfunktion und Drogenabhangigkeit nicht beobachtet werden.

Objectives: to investigate the prevalence and risk behaviors by means of reporting of sexually transmitted diseases among crack users.Method: cross-sectional study carried out with 588 crack users in a referral care unit for the treatment of chemical dependency. Data were collected by means of face-to-face interview and analyzed using Stata statistical software, version 8.0.Results: of the total participants, 154 (26.2%; 95% CI: 22.8-29.9) reported antecedents of sexually transmitted diseases. Ages between 25 and 30 years (RP: 2.1; 95% CI: 1.0-4.0) and over 30 years (RP: 3.8; 95% CI: 2.1-6.8), alcohol consumption (RP: 1.9; 95% CI: 1.1-3.3), antecedents of prostitution (RP: 1.9; 95% CI: 1.3-2.9) and sexual intercourse with person living with human immunodeficiency virus/AIDS (RP: 2.7; 95% CI: 1.8-4.2) were independently associated with reporting of sexually transmitted diseases.Conclusion: the results of this study suggest high risk and vulnerability of crack users for sexually transmitted diseases. ResumoObjetivos:investigar a prevalência e comportamentos de risco através do relato de doenças sexualmente transmissíveis em usuários de crack.Método:estudo transversal, realizado com 588 usuários de crack, de uma unidade de referência para tratamento de dependência química. Os dados foram obtidos por meio de entrevista face a face e analisados em programa estatístico Stata, versão 8.0.Resultados:do total de participantes, 154 (26,2%; IC 95%: 22,8-29,9) referiram antecedentes de doenças sexualmente transmissíveis. Idade entre 25 e 30 anos (RP: 2,1; IC 95%: 1,0-4,0) e superior a 30 anos (RP: 3,8; IC 95%: 2,1-6,8), consumo de álcool (RP: 1,9; IC 95%: 1,1-3,3), antecedentes de prostituição (RP: 1,9; IC 95%: 1,3-2,9) e relação sexual com pessoa vivendo com o vírus da imunodeficiência humana/aids (RP: 2,7; IC 95%: 1,84,2) foram independentemente associados ao relato de doenças sexualmente transmissíveis.Conclusão:os resultados deste estudo sugerem elevado risco e vulnerabilidade dos usuários de crackpara as doenças sexualmente transmissíveis. ResumenObjetivos:investigar la prevalencia y las conductas de riesgo a través del informe de las enfermedades de transmisión sexual entre los usuarios de crack.Método:estudio transversal con 588 usuarios de crack, de una unidad de referencia para el tratamiento de la dependencia química. Los datos fueron obtenidos a través de entrevista cara a cara y se analizaron utilizando el programa estadístico Stata, versión 8.0.Resultados:del total de participantes, 154 (26,2%; IC 95%: 22,8-29,9) informaron antecedentes de enfermedades de transmisión sexual. Edad entre 25 y 30 años (RP: 2,1; IC9 5%: 1,0-4,0) y superior a 30 años (RP: 3,8; IC 95%: 2,1-6,8), consumo de alcohol (OR: 1,9; IC 95%: 1,1-3,3), antecedentes de prostitución (RP: 1,9; IC 95%: 1,3-2,9) y relaciones sexuales con persona viviendo con el virus de inmunodeficiencia humana/ SIDA (RP: 2,7; IC 95%: 1,8-4,2) se asociaron de forma independiente con la notificación de las enfermedades de transmisión sexual.Conclusión:los resultados de este estudio sugieren alto riesgo y la vulnerabilidad de los usuarios de crackpara las enfermedades de transmisión sexual.

Human drug use involves repeated choices to take drugs or to engage in alternative behaviors. The purpose of this study was to examine how response cost for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance) and how ‘free’ doses (with minimal response cost) affected cocaine choice. Two laboratory studies of cocaine self-administration were conducted in a group of humans who were habitual cocaine smokers and in a group of rhesus monkeys that intravenously self-administered cocaine. Nine human cocaine smokers who were not seeking treatment for their cocaine were repeatedly presented with the choice to smoke 25 mg cocaine base or play a game of chance for a monetary bonus paid at study completion. The response cost for choosing cocaine varied (up to 4000 responses/dose) and the number of game plays varied (up to 8). In this sample of humans, increasing either the response cost for cocaine or increasing the value of the alternative reinforcer did not significantly affect cocaine choice, while increasing both simultaneously slightly decreased cocaine choice and increased choice of the alternative. In monkeys, the dose–response function for cocaine self-administration (10 choices of 0.0125–0.1 mg/kg/infusion vs. candy coated chocolate) was steep and we failed to achieve a 50/50 cocaine/candy choice even after substantially manipulating cost and number of candies available. Providing a large ‘free’ self-administered cocaine dose to humans did not significantly affect cocaine choice, whereas in monkeys, a large free dose of cocaine decreased cocaine choice when higher doses of cocaine were available for self-administration. The present results demonstrate that in the laboratory, it is difficult to modify on-going cocaine self-administration behavior in both humans and non-human primates.

Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

Like other monoamine releasers such as D-amphetamine, chronic treatment with phenmetrazine can attenuate cocaine self-administration in monkeys.The present studies extended this finding to rodents and to cocaine-primed reinstatement, a putative laboratory animal model of relapse.In experiment 1, rats self-administered food pellets or injections of 0.19 mg/kg cocaine (i.v.) under a progressive-ratio schedule. When responding was stable, subcutaneous osmotic pumps were implanted containing saline or (+)-phenmetrazine (25 or 50 mg/kg per day). In experiment 2, rats self-administered injections of 0.75 mg/kg cocaine under a fixed-ratio 1 schedule in daily 6-h sessions. When responding was stable, rats were removed from the self-administration environment for 7 days and treated continuously with saline, 5 mg/kg per day D-amphetamine or phenmetrazine (25 or 50 mg/kg per day) via osmotic pumps. Rats were then returned to the self-administration context while treatment continued, and responding was extinguished by removing response-contingent stimulus changes and cocaine injections. Once responding was extinguished, reinstatement tests were conducted using cocaine injections (10 mg/kg i.p.).Phenmetrazine decreased self-administration of cocaine, but not food pellets, during the 14-day treatment period; effects persisted for several days after treatment was discontinued. Moreover, cocaine-induced increases in responding during the reinstatement test were attenuated by D-amphetamine and both phenmetrazine doses.These results extend the study of the effects of phenmetrazine on cocaine self-administration to a rodent model, and provide further support for the use of monoamine releasers as agonist medications for cocaine abuse.

Adaptations in glutamate signaling within the brain’s reward circuitry are observed following withdrawal from several abused drugs, including cocaine. These include changes in intrinsic cellular excitability, glutamate release, and glutamate uptake. Pharmacological or optogenetic reversal of these adaptations have been shown to reduce measures of cocaine craving and seeking, raising the hypothesis that regulation of glutamatergic signaling represents a viable target for the treatment of substance use disorders. Here, we tested the hypothesis that administration of the compound riluzole, which regulates glutamate dynamics in several ways, would reduce cocaine seeking in the rat self-administration and reinstatement model of addiction. Riluzole dose-dependently inhibited cue- and cocaine-primed reinstatement to cocaine, but did not affect locomotor activity or reinstatement to sucrose seeking. Moreover, riluzole reversed bidirectional cocaine-induced adaptations in intrinsic excitability of prelimbic (PL) and infralimbic (IL) pyramidal neurons; a cocaine-induced increase in PL excitability was decreased by riluzole, and a cocaine-induced decrease in IL excitability was increased to normal levels. Riluzole also reversed the cocaine-induced suppression of the high-affinity glutamate transporter 1 (EAAT2/GLT-1) in the nucleus accumbens (NAc). GLT-1 is responsible for the majority of glutamate uptake in the brain, and has been previously reported to be downregulated by cocaine. These results demonstrate that riluzole impairs cocaine reinstatement while rectifying several cellular adaptations in glutamatergic signaling within the brain’s reward circuitry, and support the hypothesis that regulators of glutamate homeostasis represent viable candidates for pharmacotherapeutic treatment of psychostimulant relapse.

The chronic and relapsing nature of addiction suggests that drugs produce persistent adaptations in the brain that make individuals with drug addiction particularly sensitive to drug-related cues and stress and incapable of controlling drug-seeking and drug-taking behavior. In animal models, several long-lasting neuroadaptations have been described. However, few studies have used brain-imaging techniques to provide a complete picture of brain functioning in the course of withdrawal from cocaine. In this study, we allowed rats to self-administer cocaine under short-access (1-h/day) or long-access (6-h/day) conditions and used 2-deoxy-2-(18F)fluoro-d-glucose (18FDG) positron emission tomography scanning to investigate the longitudinal changes in metabolic activity 1 and 4 weeks after discontinuation of cocaine self-administration. We found that compared to naive rats, both long-access and short-access rats showed significant disruptions in basal brain metabolic activity. However, compared to short-access, long-access rats showed more intense, and long-lasting neuroadaptations in a network of brain areas. In particular, abstinence from extended access to cocaine was associated with decreased metabolic activity in the anterior cingulate cortex, the insular cortex, and the dorsolateral striatum, and increased metabolic activity in the mesencephalon, amygdala, and hippocampus. This pattern is strikingly similar to that described in humans that has led to the proposal of the Impaired Response Inhibition and Salience Attribution model of addiction. These results demonstrate that extended access to cocaine leads to persistent neuroadaptations in brain regions involved in motivation, salience attribution, memory, stress, and inhibitory control that may underlie increased risks of relapse.

Recent epidemiological data suggest a resurgence in cocaine use (CU) and cocaine-related problems in the United States. Demographic trends and correlates of problem CU are needed to determine potential factors that may be influencing the increased trend and to inform targeted prevention and intervention strategies.Trends in any past-year CU, weekly CU, and cocaine use disorder (CUD) were examined among persons aged ≥12 years using the National Survey on Drug Use and Health from 2011 to 2015. Logistic regression analyses were used to determine correlates of past-year and weekly CU and CUD among adolescents and adults.The prevalence of past-year CU from 2011 to 2015 increased among females, ages 18-25, ages ≥50, non-Hispanic Blacks, and persons reporting low income, past-year tobacco use, past-year alcohol use, and past-month binge and heavy alcohol use. The prevalence of weekly CU increased among persons aged ≥50 years and persons reporting past-month heavy alcohol use. A significant increase in the prevalence of CUD was only found among persons aged ≥50 years. Adjusted logistic regression showed that older age, large metropolitan residence, past-year tobacco, alcohol, cannabis, and heroin use, and major depressive episode were associated with increased odds of CU or CUD among both adolescents and adults; however, sex and race/ethnicity correlates differed among adolescents and adults.Findings have implications for increased monitoring of CU-related indicators among some high-risk groups, such as females, older adults, Blacks, and polysubstance users. Targeted screening and intervention strategies among these population subgroups may be needed.

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.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.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.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.

The Theory of Planned Behavior (TPB) can provide insights into perceived need for cocaine treatment among African American cocaine users.A cross-sectional community sample of 400 (50% rural) not-in-treatment African-American cocaine users was identified through respondent-driven sampling in one urban and two rural counties in Arkansas. Measures included self-reports of attitudes and beliefs about cocaine treatment, perceived need and perceived effectiveness of treatment, and positive and negative cocaine expectancies. Normative beliefs were measured by perceived stigma and consequences of stigma regarding drug use and drug treatment. Perceived control was measured by readiness for treatment, prior drug treatment, and perceived ability to cut down on cocaine use without treatment.Multiple regression analysis found that older age (standardized regression coefficient β=0.15, P0.001), rural residence (β=-0.09, P=0.025), effectiveness of treatment (β=0.39, P0.001), negative cocaine expectancies (β=0.138, P=0.003), experiences of rejection (β=0.18, P0.001), need for secrecy (β=0.12, P=0.002), and readiness for treatment (β=0.15, P0.001) were independently associated with perceived need for cocaine treatment.TPB is a relevant model for understanding perceived need for treatment among African-American cocaine users. Research has shown perceived need to be a major correlate of treatment participation. Study results should be applicable for designing interventions to encourage treatment participation.

Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine's pharmacodynamic effects.This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness.Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes.

Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure.The objective of the present study is to determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats.Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11-13 sessions.Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion, and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline.Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders).

Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24h postinfusion.Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48h were received: lorazepam (2mg) and two doses of ketamine (0.41mg/kg and 0.71mg/kg, with the former dose always preceding the latter). Infusions were followed within 15min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure).Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71mg/kg was associated with significantly higher HMS scores than was the 0.41mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24h postinfusion.These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

Elevated rates of borderline personality disorder (BPD) have been found among individuals with substance use disorders (SUDs), especially cocaine-dependent patients. Evidence suggests that cocaine-dependent patients with BPD are at greater risk for negative clinical outcomes than cocaine-dependent patients without BPD and BPD-SUD patients dependent on other substances. Despite evidence that cocaine-dependent patients with BPD may be at particularly high risk for negative SUD outcomes, the mechanisms underlying this risk remain unclear. The present study sought to address this gap in the literature by examining cocaine-related attentional biases among cocaine-dependent patients with (n = 22) and without (n = 36) BPD. On separate days, participants listened to both a neutral and a personally-relevant emotionally evocative (i.e., trauma-related) script and then completed a dot-probe task with cocaine-related stimuli. Findings revealed a greater bias for attending to cocaine-related stimuli among male cocaine-dependent patients with (vs. without) BPD following the emotionally evocative script. Study findings suggest the possibility that cocaine use may have gender-specific functions among SUD patients with BPD, with men with BPD being more likely to use cocaine to decrease contextually induced emotional distress. The implications of our findings for informing future research on cocaine use among patients with BPD are discussed.

Cocaine remains one of the most addictive substances of abuse and one of the most difficult to treat. Although increasingly sophisticated experimental and technologic advancements in the last several decades have yielded a large body of clinical and preclinical knowledge on the direct effects of cocaine on the brain, we still have a relatively incomplete understanding of the neurobiological processes that occur when drug use is discontinued. The goal of this manuscript is to review both clinical and preclinical data related to abstinence from cocaine and discuss the complementary conclusions that emerge from these different levels of inquiry. This commentary will address observed alterations in neural function, neural structure, and neurotransmitter system regulation that are present in both animal models of cocaine abstinence and data from recovering clinical populations. Although these different levels of inquiry are often challenging to integrate, emerging data discussed in this commentary suggest that from a structural and functional perspective, the preservation of cortical function that is perhaps the most important biomarker associated with extended abstinence from cocaine.

Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis.This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment.We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes.Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward.These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.

Medications decreasing central noradrenergic activity have been associated with attenuation of cocaine effects.This pilot study examined the efficacy of doxazosin versus placebo for reducing cocaine use in treatment-seeking cocaine dependent persons.We screened 108 cocaine dependent subjects and assigned 35 participants to receive either doxazosin (8mg/day) or placebo for 13 weeks. Participants were titrated on the study medication according to two different schedules. During the initial phase of the study, patients were titrated onto the study medication over an 8-week period (DOX-slow). After reviewing data from our human laboratory study, a second phase was initiated, wherein titration was accelerated to a 4-week period (DOX-fast). All participants received weekly cognitive behavioral therapy. Urine toxicology was performed thrice weekly.Baseline subject characteristics were comparable. Thirty subjects entered the study: 8 subjects in DOX-slow, 9 subjects in DOX-fast, and 13 subjects in placebo. Total number of cocaine-negative urines was significantly increased in the DOX-fast group; and percentage of total cocaine-negative urines by group were 10% for DOX-slow group, 35% for DOX-fast group, and 14% for placebo (χ(2)=36.3, df=2, p0.0001). The percentage of participants achieving two or more consecutive weeks of abstinence by group was 0% for DOX-slow group, 44% for DOX-fast group, and 7% for placebo (χ(2)=7.35, df=2, p0.023).This pilot study suggests the potential efficacy of doxazosin when rapidly titrated in reducing cocaine use.

Various dimensions of impulsivity have been linked to substance abuse and dependence, both as consequences of, and as predisposing factors to addiction. With respect to the latter, they may be quantitative indicators of liability for substance use disorders (SUD) and aid in determining underlying genetic influences. We have previously determined that inhibitory control over impulsive responding, as measured by a reversal learning task, is heritable and under substantial genetic control, however their role as explaining variables for aspects of SUD have not been well explored.The aim of this study was to test for an association between genetically determined differences in inhibitory control and addiction-related phenotypes, such that phenotypes of poor inhibitory control would predict propensity for elevated operant drug-seeking and -taking behaviors.Mice from BxD strains with either good reversal learning (GRL) or poor reversal learning (PRL) ability were tested for intravenous cocaine self-administration under FR1, FR2, and FR5 reinforcement schedules. Additionally, locomotor responses to experimenter-delivered cocaine were assessed.Compared to GRL strains, PRL strains acquired self-administration behavior more rapidly and administered cocaine at greater rates under all schedules of reinforcement, without any differences in discrimination index. In addition, PRL mice also exhibited increased responding during time-out periods. PRL strains also showed larger locomotor responses to 10 or 20 mg/kg injections of cocaine.These studies demonstrate that heritable strain differences in inhibitory control do influence drug self-administration, thus suggest that genetically driven impulsivity of this type may predispose susceptibility to drug abuse and addiction.

Resumen Objetivos Conocer la prevalencia de consumo de cocaina en una muestra de estudiantes universitarios y analizar el uso de otras sustancias por parte de los consumidores habituales de esta droga. Metodo Estudio observacional, descriptivo y transversal realizado en las Facultades de Educacion, Psicologia y Ciencias y las Escuelas de Enfermeria y Politecnica Superior de la Universidad de Girona. La muestra analizada fue de 2.139 estudiantes de primer ciclo. Las variables de estudio fueron demograficas y especificas sobre el consumo de drogas. Para la recogida de datos se utilizo un cuestionario de elaboracion propia que agrupa informacion sobre el genero, la edad y la facultad de procedencia de los participantes, asi como su estatus de consumo. Resultados El 47,2% son chicos y el 52,8% son chicas de edades comprendidas entre los 17 y los 35 anos (media = 21 anos y DE = 3,14). Un 1% de los participantes informan que son consumidores habituales de cocaina. Nueve de cada diez estudiantes consumen, ademas, alcohol (95,2%) y cannabis (90,5%) de forma habitual. Conclusiones Se constata que los estudiantes universitarios mantienen conductas de riesgo para la salud como es el consumo de cocaina. Entre los consumidores de esta sustancia el uso habitual de otras drogas esta mas extendido que entre los que no la utilizan. Seria necesario plantear el desarrollo de programas especificos para prevenir el consumo de drogas en estudiantes universitarios.

Nasal columella defects can significantly impair aesthetic appearance. Columella reconstruction can be very challenging for surgeons, especially if due to cocaine abuse. The case of a 32-year-old male patient with subtotal columellar necrosis secondary to cocaine abuse is presented. An inferiorly based philtral advancement flap was performed to cover the defect. Aesthetic outcome was the primary goal of surgery. Reconstruction led to good aesthetic and functional results.