Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Sociodemographic and clinical profile of crack cocaine treatment-seeking individuals living in "Crackland", Brazil / Perfil sociodemográfico e clínico de indivíduos em busca de tratamento para o uso de crack que vivem na "Cracolândia"

OBJECTIVE: São Paulo's Crackland is the biggest and oldest open drug use scene in Brazil, yet little is known about the profile of crack cocaine treatment-seeking individuals living in this region. The aim of this crossectional study was to describe the demographics and clinical characteristics of treatment-seeking crack users living in the Crackland region. METHODS: A sample of nighty eight individuals were screened for DSM-V substance use disorders, including substance use, impulsiveness, and psychiatric symptoms. Recent crack cocaine use was also tested using biologic specimens. RESULTS: Results indicated severe social vulnerability, as participants experienced high rates of homelessness (46.9%), unstable housing (50%), unemployment (60.4%) and early school drop-out (27.5%). The average age of crack use onset was 20 years (SD = 6.9) and the mean duration of continuous crack use was 15 years (SD = 9.7). Most participants presented with concomitant mental health disorders, particularly alcohol use disorder (87.8%), as well high rates of psychiatric symptomatology and impulsiveness. More than half of the sample reported at least one previous inpatient (73.5%) and outpatient (65.3%) addiction treatment attempt. CONCLUSION: This population profile should inform mental healthcare services, promoting the provision of tailored assistance by targeting specific demands at all levels of treatment.

OBJETIVO: Localizada em São Paulo, a Cracolândia é o maior e mais antigo cenário aberto de uso de drogas do Brasil. Ainda assim, pouco se sabe sobre o perfil dos indivíduos que vivem nessa região e buscam tratamento para crack. O objetivo deste estudo transversal foi descrever características demográficas e clínicas de usuários de crack vivendo na região da Cracolândia que estão em busca de tratamento. MÉTODOS: Noventa e oito indivíduos foram avaliados para transtornos por uso de substâncias do DSM-V, padrão de uso de substâncias, impulsividade e sintomatologia psiquiátrica. O uso recente de crack também foi determinado por meio de coleta de amostras toxicológicas. RESULTADOS: Os resultados indicaram grave vulnerabilidade social, com significativas prevalências de falta de moradia (46,9%), moradia instável (50%), desemprego (60,4%) e abandono escolar precoce (27,5%). A idade média de início do uso de crack foi de 20 anos (DP = 6,9) e a duração média do uso contínuo do crack foi de 15 anos (DP = 9,7). A maioria dos participantes apresentou alguma comorbidade psiquiátrica, particularmente transtorno por uso de álcool (87,8%), bem como altas taxas de sintomatologia psiquiátrica e impulsividade. Mais da metade da amostra relatou pelo menos uma tentativa anterior de tratamento por internação (73,5%) e ambulatorial (65,3%). CONCLUSÃO: Os achados desse estudo permitem um maior entendimento do perfil e das necessidades de usuários de crack vivendo na região da Cracolândia e podem ajudar serviços de saúde especializados em dependência química a promoverem uma assistência mais direcionada às demandas específicas dessa população.

Electroacupuncture prevents cocaine-induced conditioned place preference reinstatement and attenuates ΔFosB and GluR2 expression.

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.

The effect of N-acetylcysteine and working memory training on glutamate concentrations in the dACC and rACC in regular cocaine users - A randomized proof of concept study.

INTRODUCTION: Current treatments for cocaine use disorder (CUD) are not very effective and better treatments are needed. This study investigates the effectiveness of a combined intervention that targets the assumed underlying glutamate pathology in cocaine users. To this end, the combined effects of N-acetylcysteine (NAC) and working memory (WM) training on glutamate concentrations in the dorsal and rostral ACC were investigated in a randomized, double-blind placebo-controlled design. METHODS: In this study, 38 regular cocaine-using men were randomized to either 25-days with 2400 mg/day NAC and WM-training or 25 days with placebo with WM-training. Cocaine use, impulsivity, and glutamate concentrations in the dACC and rACC using proton Magnetic Resonance Spectroscopy were assessed at baseline and after treatment. RESULTS: Twenty-four participants completed the study, of which 9 received NAC and 15 received placebo. There were no baseline correlations of glutamate concentrations in the dACC or rACC with cocaine use measures or impulsivity. Additionally, there were no effects of NAC, WM-training, or the combination thereof on (changes in) glutamate concentrations in the dACC or rACC. DISCUSSION: This randomized proof of concept study could not confirm our hypotheses. Possible explanations are insufficient power and the possible absence of deviant baseline glutamate concentrations in the included participants. Future studies should consider larger samples and a non-using control group to confirm baseline deviations in glutamate in cocaine users.

Effectiveness of psychosocial interventions for reducing parental substance misuse.

BACKGROUND: Parental substance use is a substantial public health and safeguarding concern. There have been a number of trials of interventions relating to substance-using parents that have sought to address this risk factor, with potential outcomes for parent and child. OBJECTIVES: To assess the effectiveness of psychosocial interventions in reducing parental substance use (alcohol and/or illicit drugs, excluding tobacco). SEARCH METHODS: We searched the following databases from their inception to July 2020: the Cochrane Drugs and Alcohol Group Specialised Register; CENTRAL; MEDLINE; Embase; PsycINFO; CINAHL; Applied Social Science (ASSIA); Sociological Abstracts; Social Science Citation Index (SSCI), Scopus, ClinicalTrials.gov, WHO ICTRP, and TRoPHI. We also searched key journals and the reference lists of included papers and contacted authors publishing in the field. SELECTION CRITERIA: We included data from trials of complex psychosocial interventions targeting substance use in parents of children under the age of 21 years. Studies were only included if they had a minimum follow-up period of six months from the start of the intervention and compared psychosocial interventions to comparison conditions. The primary outcome of this review was a reduction in the frequency of parental substance use. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 22 unique studies with a total of 2274 participants (mean age of parents ranged from 26.3 to 40.9 years), examining 24 experimental interventions. The majority of studies intervened with mothers only (n = 16; 73%). Heroin, cocaine, and alcohol were the most commonly reported substances used by participants. The interventions targeted either parenting only (n = 13; 59%); drug and alcohol use only (n = 5; 23%); or integrated interventions which addressed both (n = 6; 27%). Half of the studies (n = 11; 50%) compared the experimental intervention to usual treatment. Other comparison groups were minimal intervention, attention controls, and alternative intervention. Eight of the included studies reported data relating to our primary outcome at 6- and/or 12-month follow-up and were included in a meta-analysis. We investigated intervention effectiveness separately for alcohol and drugs. Studies were found to be mostly at low or unclear risk for all 'Risk of bias' domains except blinding of participants and personnel and outcome assessment.  We found moderate-quality evidence that psychosocial interventions are probably more effective at reducing the frequency of parental alcohol misuse than comparison conditions at 6-month (mean difference (MD) -0.32, 95% confidence interval (CI) -0.51 to -0.13; 6 studies, 475 participants) and 12-month follow-up (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.03; 4 studies, 366 participants). We found a significant reduction in frequency of use at 12 months only (SMD -0.21, 95% CI -0.41 to -0.01; 6 studies, 514 participants, moderate-quality evidence). We examined the effect of the intervention type. We found low-quality evidence that psychosocial interventions targeting substance use only may not reduce the frequency of alcohol (6 months: SMD -0.35, 95% CI -0.86 to 0.16; 2 studies, 89 participants and 12 months: SMD -0.09, 95% CI -0.86 to 0.61; 1 study, 34 participants) or drug use (6 months: SMD 0.01, 95% CI -0.42 to 0.44; 2 studies; 87 participants and 12 months: SMD -0.08, 95% CI -0.81 to 0.65; 1 study, 32 participants). A parenting intervention only, without an adjunctive substance use component, may not reduce frequency of alcohol misuse (6 months: SMD -0.21, 95% CI -0.46 to 0.04, 3 studies; 273 participants, low-quality evidence and 12 months: SMD -0.11, 95% CI -0.64 to 0.41; 2 studies; 219 participants, very low-quality evidence) or frequency of drug use  (6 months: SMD 0.10, 95% CI -0.11 to 0.30; 4 studies; 407 participants, moderate-quality evidence and 12 months: SMD -0.13, 95% CI -0.52 to 0.26; 3 studies; 351 participants, very low-quality evidence). Parents receiving integrated interventions which combined both parenting- and substance use-targeted components may reduce alcohol misuse with a small effect size (6 months: SMD -0.56, 95% CI -0.96 to -0.16 and 12 months: SMD -0.42, 95% CI -0.82 to -0.03; 2 studies, 113 participants) and drug use (6 months: SMD -0.39, 95% CI -0.75 to -0.03 and 12 months: SMD -0.43, 95% CI -0.80 to -0.07; 2 studies, 131 participants). However, this evidence was of low quality. Psychosocial interventions in which the child was present in the sessions were not effective in reducing the frequency of parental alcohol or drug use, whilst interventions that did not involve children in any of the sessions were found to reduce frequency of alcohol misuse (6 months: SMD -0.47, 95% CI -0.76 to -0.18; 3 studies, 202 participants and 12 months: SMD -0.34, 95% CI -0.69 to 0.00; 2 studies, 147 participants) and drug use at 12-month follow-up (SMD -0.34, 95% CI -0.69 to 0.01; 2 studies, 141 participants). The quality of this evidence was low. Interventions appeared to be more often beneficial for fathers than for mothers. We found low- to very low-quality evidence of a reduction in frequency of alcohol misuse for mothers at six months only (SMD -0.27, 95% CI -0.50 to -0.04; 4 studies, 328 participants), whilst in fathers there was a reduction in frequency of alcohol misuse (6 months: SMD -0.43, 95% CI -0.78 to -0.09; 2 studies, 147 participants and 12 months: SMD -0.34, 95% CI -0.69 to 0.00; 2 studies, 147 participants) and drug use (6 months: SMD -0.31, 95% CI -0.66 to 0.04; 2 studies, 141 participants and 12 months: SMD -0.34, 95% CI -0.69 to 0.01; 2 studies, 141 participants). AUTHORS' CONCLUSIONS: We found moderate-quality evidence that psychosocial interventions probably reduce the frequency at which parents use alcohol and drugs. Integrated psychosocial interventions which combine parenting skills interventions with a substance use component may show the most promise. Whilst it appears that mothers may benefit less than fathers from intervention, caution is advised in the interpretation of this evidence, as the interventions provided to mothers alone typically did not address their substance use and other related needs. We found low-quality evidence from few studies that interventions involving children are not beneficial.

Transcranial Magnetic Stimulation: A review about its efficacy in the treatment of alcohol, tobacco and cocaine addiction.

Substance Use Disorder (SUD) is a chronic and relapsing disease characterized by craving, loss of control, tolerance and physical dependence. At present, the combination of pharmacotherapy and psychosocial intervention is the most effective management strategy in preventing relapse to reduce dropout rates and promote abstinence in SUD patients. However, only few effective medications are available. Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique that modulates the cellular activity of the cerebral cortex through a magnetic pulse applied on selected brain areas. Recently, the efficacy of TMS has been investigated in various categories of SUD patients. The present review analyzes the application of repetitive TMS in patients with alcohol, tobacco, and cocaine use disorder. Although the number of clinical studies is still limited, repetitive TMS yields encouraging results in these patients, suggesting a possible role of TMS in the treatment of SUD.

O cuidado com gestantes que usam drogas: análise de práticas em políticas públicas de saúde no Sul do Brasil / Care of pregnant women who use drugs: analysis of practices in public health policies in southern Brazil

Resumo Este artigo tem como objetivo debater práticas de cuidado com gestantes usuárias de drogas nas políticas públicas, considerando o modo como relações de gênero influenciam as práticas de saúde. Partimos de uma pesquisa etnográfica realizada em uma unidade de internação psiquiátrica de um Hospital público e em um Consultório na Rua, no Rio Grande do Sul, focando na atenção voltada a gestantes que fazem uso de crack nesses espaços. Fundamentamo-nos teoricamente em estudos feministas interseccionais e descoloniais, bem como na noção de Economia Moral. O uso de drogas para fins recreativos por mulheres é comumente considerado inapropriado e motivo de estigmatizações, pois, ao afastarem-se da normatividade do que se espera sobre ser mulher, elas são, geralmente, julgadas moralmente. Junto a isso, a análise aponta para o modo como a produção biopolítica de um imaginário único sobre a maternidade incide nas maneiras segundo as quais as políticas públicas operam em relação às mulheres, o que se torna um ponto fundamental ao se considerar o contexto social no qual elas estão inseridas. Assim, o artigo destaca a importância de análises interseccionais de gênero, raça e classe no campo das políticas públicas de drogas.

Abstract This paper aims to discuss care practices used with pregnant drug users in public policies, considering how gender relations influence health practices. This is an ethnographic research on attention to pregnant women, who are crack users, in a psychiatric unit in a public hospital and a Clinic in the Street in Rio Grande do Sul. This research was based on intersectional and decolonial feminist studies, as well as the notion of moral economy. The use of drugs by women for recreational purposes is often considered inappropriate and grounds for stigma because it deviates from the normativity of what is expected from being a woman, that are often morally judged. Moreover, the analysis points out how the biopolitical production of a unique imaginary o nmotherhood affects the way in which public policies act towards women. This becomes a fundamental point when considering the social context in which these women are inserted. Thus, the article highlights the importance of intersectional analysis of gender, race and class for public drug policies.

[Asthma and cannabis, cocaine or heroin use]. / Asthme et usage de cannabis, de cocaïne ou d'héroïne.

INTRODUCTION: The use of cannabis, cocaine or heroin can be responsible for many respiratory complications including asthma. OBJECTIVES: The aim of this systematic literature review of data was to expose the relations between cannabis, cocaine or heroin use and asthma. RESULTS: Cannabis, cocaine or heroin use by inhalation may be responsible for respiratory symptoms (cough, wheezing), asthma onset, acute asthma exacerbations (which may require intubation and invasive ventilation) or deaths related to asthma. Lower adherence to asthma treatment is also observed. Cannabis induces a rapid bronchodilator effect. In contrast, its chronic use may induce a decrease in specific airway conductance. Studies on forced expiratory volume in one second (FEV1) reduction or decline are discordant. CONCLUSION: Cannabis, cocaine or heroin use must be considered in cases of acute respiratory symptoms or asthma exacerbation in young persons and practitioners must help illicit substance users to stop their consumption.

Effects of childhood trauma on BDNF and TBARS during crack-cocaine withdrawal

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal. Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

Living Fatherhood in Adults Addicted to Substances: A Qualitative Study of Fathers in Psycho-Rehabilitative Drug Addiction Treatment for Heroin and Cocaine.

The research aims to investigate the emotional experiences of the individuals who use drugs in terms of their parenting role as father, within a rehabilitative context. The study aims to analyze how dependence affects the exercise of the parental role, specifically paternity, with the aim of offering an overview of the father-son relationship while considering the possible limitations that characterize those who are forced to live parenting in an atypical way. It is necessary to help individuals who use drugs to be able to help them in life with the goal of establish a better parenting awareness and a good relationship with their father and their children. The research work made use of qualitative tools, specifically semi-structured interview, which was administered to a sample of 18 fathers that were treated in a rehabilitation clinic for individuals who use drugs. The used semi-structured interview made it possible to analyze the perception of participants about their paternity, the quality of the relationship with their father and their children, and the influence that the narcotic substance has generated in the relationship with their father and with their children.

Baseline cocaine demand predicts contingency management treatment outcomes for cocaine-use disorder.

Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants (N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [Q0], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q0 (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q0 revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder.

Nationally, it was estimated that 11.4 million people misused opioids in 2017 with more than 47,000 opioid-related deaths. Although medication-assisted treatment (MAT) has been effective in enhancing treatment retention and decreasing frequency of opioid use, relapse rates for opioids and other substances remain high, emphasizing the importance of investigating novel interventions to augment MAT. One potential treatment approach is repetitive transcranial magnetic stimulation (rTMS)-a noninvasive, electrophysiological method of neuromodulation. Recently published studies of rTMS in individuals with alcohol, nicotine, and cocaine use disorder have suggested that this treatment shows promise in reducing cravings and substance use. The literature specific to rTMS and opioid use disorder (OUD) is limited to a single published study in heroin users, which showed that a single session of rTMS to the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving, with a further reduction following 5 consecutive days of rTMS. The following case report involved a 25-year-old Caucasian male diagnosed with OUD and cocaine use disorder. This subject continued to demonstrate ongoing substance use despite participating in comprehensive MAT with buprenorphine/naloxone in combination with psychosocial interventions. He was administered 7 separate sessions of rTMS targeting the left DLPFC. Substance-related cues were presented prior to, during, and following these rTMS administration sessions and the subject rated his substance cravings via a 100-point Visual Analog Scale. When compared with his cue-induced craving ratings, there was a mean reduction in craving for heroin and cocaine by ∼60% to 82% following the 7 administration sessions. Although this is a single case, further investigation of rTMS as an augmentation strategy for OUD and polysubstance use is warranted. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Systemic Safety of a Recombinant AAV8 Vector for Human Cocaine Hydrolase Gene Therapy: A Good Laboratory Practice Preclinical Study in Mice.

Cocaine addiction continues to impose major burdens on affected individuals and broader society but is highly resistant to medical treatment or psychotherapy. This study was undertaken with the goal of Food and Drug Administration (FDA) permission for a first-in-human clinical trial of a gene therapy for treatment-seeking cocaine users to become and remain abstinent. The approach was based on intravenous administration of AAV8-hCocH, an adeno-associated viral vector encoding a modified plasma enzyme that metabolizes cocaine into harmless by-products. To assess systemic safety, we conducted "Good Laboratory Practice" (GLP) studies in cocaine-experienced and cocaine-naive mice at doses of 5E12 and 5E13 vector genomes/kg. Results showed total lack of viral vector-related adverse effects in all tests performed. Instead, mice given one injection of AAV8-hCocH and regular daily injections of cocaine had far less tissue pathology than cocaine-injected mice with no vector treatment. Biodistribution analysis showed the vector located almost exclusively in the liver. These results indicate that a liver-directed AAV8-hCocH gene transfer at reasonable dosage is safe, well tolerated, and effective. Thus, gene transfer therapy emerges as a radically new approach to treat compulsive cocaine abuse. In fact, based on these positive findings, the FDA recently accepted our latest request for investigational new drug application (IND 18579).

Cocaine Use in Adolescents and Young Adults.

Cocaine use by adolescents and young adults continues to be a significant public health issue and the cause of medical and psychological morbidity and mortality. Although use rates are lower than those seen with alcohol, tobacco, and other illicit substances such as marijuana, cocaine is highly addictive and presents significant acute and long-term medical and psychological effects. This article reviews the epidemiology of cocaine use among adolescents and young adults, discusses the pharmacology and neurobiology of cocaine use and dependence, provides information regarding acute intoxication and systemic effects seen with more chronic use, and describes current assessment and treatment approaches.

Medical marijuana laws are associated with increases in substance use treatment admissions by pregnant women.

BACKGROUND AND AIMS: Between 2002 and 2014, past-month marijuana use among pregnant women in the United States increased 62%, nearly twice the growth of the general population. This growth coincides with the proliferation of state medical marijuana laws (MMLs) authorizing physicians to recommend marijuana for approved conditions. We estimated the association between MMLs and substance use treatment utilization among pregnant and non-pregnant women of reproductive age. We also examined whether the association varied across MML provisions, age groups and treatment referral sources to clarify potential pathways. DESIGN: Nation-wide administrative data from the 2002-14 Treatment Episodes Data Set Admissions, and a difference-in-differences design that exploited the staggered implementation of MMLs to compare changes in outcomes before and after implementation between MML and non-MML states. SETTING: Twenty-one MML and 27 non-MML US states. PARTICIPANTS: Pregnant and non-pregnant women aged 12-49 admitted to publicly funded specialty substance use treatment facilities. MEASUREMENTS: The primary outcome variable was the number of treatment admissions per 100 000 women aged 12-49, aggregated at the state-year level (n = 606). Admissions for marijuana, alcohol, cocaine and opioids were considered. The primary independent variable was an indicator of MML implementation in a state. FINDINGS: Among pregnant women, the rate of marijuana treatment admissions increased by 4.69 [95% confidence interval (CI) = 1.32, 8.06] in MML states relative to non-MML states. This growth was accompanied by increases in treatment admissions involving alcohol (ß = 3.19; 95% CI = 0.97, 5.410 and cocaine (ß = 2.56; 95% CI = 0.34, 4.79), was specific to adults (ß = 5.50; 95% CI = 1.52, 9.47) and was largest in states granting legal protection for marijuana dispensaries (ß = 6.37; 95% CI = -0.97, 13.70). There was no statistically significant association between MMLs and treatment admissions by non-pregnant women. CONCLUSIONS: Medical marijuana law implementation in US states has been associated with greater substance use treatment utilization by pregnant adult women, especially in states with legally protected dispensaries.

Internación compulsiva de usuarios de crack para el tratamiento de la dependencia: una revisión sistemática de la literatura / Compulsory commitment of crack users for addiction treatment: A systematic review of the literature

El estudio tuvo como objetivo discutir los conflictos de la internación compulsiva de consumidores de crack. Se realizó una revisión sistemática sobre el tratamiento compulsivo. La búsqueda fue realizada en las bases de datos: Scopus, PubMed, SciELO, Web of Science, Elsevier y Medline, así como en Google y Google Scholar, y se incluyeron publicaciones de 2000 a 2017. El desenlace primario de interés fue el uso de drogas post-tratamiento, y el secundario la reincidencia criminal pos-tratamiento. De un total de 448 estudios potenciales identificados, doce estudios cumplieron los criterios de inclusión. Se concluye que la internación compulsiva, además de ser agresiva y una forma de tratamiento ineficaz, constituye un modo de eliminación de los indeseados, constituyéndose en práctica higienista violadora de derechos humanos(AU)

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users.

BACKGROUND: Problem alcohol use is common among people who use illicit drugs (PWID) and is associated with adverse health outcomes. It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opioid overdose in PWID. OBJECTIVES: To assess the effectiveness of psychosocial interventions to reduce alcohol consumption in PWID (users of opioids and stimulants). SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and PsycINFO, from inception up to August 2017, and the reference lists of eligible articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction, International Harm Reduction Association, International Conference on Alcohol Harm Reduction and American Association for the Treatment of Opioid Dependence; and 2) online registers of clinical trials: Current Controlled Trials, ClinicalTrials.gov, Center Watch and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: We included randomised controlled trials comparing psychosocial interventions with other psychosocial treatment, or treatment as usual, in adult PWIDs (aged at least 18 years) with concurrent problem alcohol use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven trials (825 participants). We judged the majority of the trials to have a high or unclear risk of bias.The psychosocial interventions considered in the studies were: cognitive-behavioural coping skills training (one study), twelve-step programme (one study), brief intervention (three studies), motivational interviewing (two studies), and brief motivational interviewing (one study). Two studies were considered in two comparisons. There were no data for the secondary outcome, alcohol-related harm. The results were as follows.Comparison 1: cognitive-behavioural coping skills training versus twelve-step programme (one study, 41 participants)There was no significant difference between groups for either of the primary outcomes (alcohol abstinence assessed with Substance Abuse Calendar and breathalyser at one year: risk ratio (RR) 2.38 (95% confidence interval [CI] 0.10 to 55.06); and retention in treatment, measured at end of treatment: RR 0.89 (95% CI 0.62 to 1.29), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was very low.Comparison 2: brief intervention versus treatment as usual (three studies, 197 participants)There was no significant difference between groups for either of the primary outcomes (alcohol use, measured as scores on the Alcohol Use Disorders Identification Test (AUDIT) or Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) at three months: standardised mean difference (SMD) 0.07 (95% CI -0.24 to 0.37); and retention in treatment, measured at three months: RR 0.94 (95% CI 0.78 to 1.13), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low.Comparison 3: motivational interviewing versus treatment as usual or educational intervention only (three studies, 462 participants)There was no significant difference between groups for either of the primary outcomes (alcohol use, measured as scores on the AUDIT or ASSIST at three months: SMD 0.04 (95% CI -0.29 to 0.37); and retention in treatment, measured at three months: RR 0.93 (95% CI 0.60 to 1.43), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low.Comparison 4: brief motivational intervention (BMI) versus assessment only (one study, 187 participants)More people reduced alcohol use (by seven or more days in the past month, measured at six months) in the BMI group than in the control group (RR 1.67; 95% CI 1.08 to 2.60). There was no difference between groups for the other primary outcome, retention in treatment, measured at end of treatment: RR 0.98 (95% CI 0.94 to 1.02), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was moderate.Comparison 5: motivational interviewing (intensive) versus motivational interviewing (one study, 163 participants)There was no significant difference between groups for either of the primary outcomes (alcohol use, measured using the Addiction Severity Index-alcohol score (ASI) at two months: MD 0.03 (95% CI 0.02 to 0.08); and retention in treatment, measured at end of treatment: RR 17.63 (95% CI 1.03 to 300.48), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low. AUTHORS' CONCLUSIONS: We found low to very low-quality evidence to suggest that there is no difference in effectiveness between different types of psychosocial interventions to reduce alcohol consumption among people who use illicit drugs, and that brief interventions are not superior to assessment-only or to treatment as usual. No firm conclusions can be made because of the paucity of the data and the low quality of the retrieved studies.

Importance of a Risk Stratification Strategy to Identify High-risk Patients Presenting With Cocaine-associated Acute Coronary Syndrome.

OBJECTIVE: Current guidelines recommend treating patients with cocaine-associated chest pain, unstable angina, or myocardial infarction similarly to patients with traditional acute coronary syndrome (ACS). Risk stratifying these patients could potentially reduce unnecessary procedures and improve resource utilization. METHODS: This is a retrospective cross-sectional analysis of 258 patients presenting with cocaine-associated ACS who underwent cardiac catheterization in a community teaching hospital between 2006 and 2015. The primary outcome was the prevalence of acute obstructive coronary artery disease (CAD) requiring percutaneous coronary intervention and coronary artery bypass grafting compared with that of patients with normal coronary or nonobstructive disease. RESULTS: Of the studied population, 36% had obstructive CAD requiring intervention and 64% were found to have normal coronaries or nonobstructive disease. Significant risk factors for obstructive CAD were older age, history of CAD, diabetes mellitus, dyslipidemia, ST-segment-elevation myocardial infarction, and troponin elevation. A logistic model was developed based on these variables, applied to the studied population, and was found to have 93% sensitivity in predicting the likelihood of obstructive CAD. CONCLUSIONS: Cardiac catheterization in patients presenting with cocaine-associated ACS may be overutilized. A predictive model based on clinical risk factors may help individualize patient care and reduce unnecessary invasive diagnostic interventions.