Crack cocaine inhalation increases seizure susceptibility by reducing acetylcholinesterase activity.

Crack cocaine is a highly addictive and potent stimulant drug. Animal studies have shown that the cholinergic system plays a role in neurotoxicity induced by cocaine or its active metabolites inhalation. Behavioral alterations associated with crack cocaine use include hyperactivity, depressed mood, and decreased seizure threshold. Here we evaluate the acetylcholinesterase (AChE) and reactive oxygen species (ROS) activity, behavioral profile, and the threshold for epileptic seizures in rats that received intrahippocampal pilocarpine (H-PILO) followed by exposure to crack cocaine (H-PILO + CRACK). Animals exposed to H-PILO + CRACK demonstrated increased severity and frequency of limbic seizures. The AChE activity was reduced in the groups exposed to crack cocaine alone (CRACK) and H-PILO + CRACK, whereas levels of ROS remained unchanged. In addition, crack cocaine exposure increased vertical locomotor activity, without changing water and sucrose intake. Short-term memory consolidation remained unchanged after H-PILO, H-PILO + CRACK, and CRACK administration. Overall, our data suggest that crack cocaine inhalation reduced the threshold for epileptic seizures in rats submitted to low doses of pilocarpine through the inhibition of AChE. Taken together, our findings can be useful in the development of effective strategies for preventing and treating the harmful effects of cocaine and crack cocaine on the central nervous system.

Neurotoxicity of crack cocaine exposure: evidence from a systematic review of in vitro and in vivo studies.

Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.

Neonatal outcomes associated with tobacco, alcohol, and crack use during pregnancy in three Neonatal Intensive Care Units.

Despite the prevalence of substance use during pregnancy, studies focusing exclusively on Neonatal Intensive Care Units (NICU) admissions remain limited. This study investigates the impact of maternal use of tobacco, alcohol, and/or crack, on neonatal outcomes among infants admitted to three Brazilian NICUs. Additionally, the investigation explores the impact of substance use on DNA damage in newborns. Over a one-year period, data from 254 newborns were collected through medical records, accompanied by blood samples. Findings revealed that 16.1% of newborns had mothers reporting substance use during pregnancy. Significant associations were found between maternal substance use and adverse neonatal outcomes, including low birth weight, preterm birth, and sexually transmitted infections. Maternal variables linked to substance use encompassed non-white skin color, low education, non-masonry housing, lower income, diseases in other children, and fewer prenatal consultations. Notably, neonatal DNA damage showed no significant association with substance use. Our results underscore the substantial impact of maternal substance use on NICU-admitted infants, emphasizing the necessity for targeted interventions that address both neonatal health and maternal well-being, thereby underscoring the crucial role of comprehensive care in NICU settings.

Safe inhalation pipe provision (SIPP): protocol for a mixed-method evaluation of an intervention to improve health outcomes and service engagement among people who use crack cocaine in England.

BACKGROUND: Over 180,000 people use crack cocaine in England, yet provision of smoking equipment to support safer crack use is prohibited under UK law. Pipes used for crack cocaine smoking are often homemade and/or in short supply, leading to pipe sharing and injuries from use of unsafe materials. This increases risk of viral infection and respiratory harm among a marginalised underserved population. International evaluations suggest crack pipe supply leads to sustained reductions in pipe sharing and use of homemade equipment; increased health risk awareness; improved service access; reduction in injecting and crack-related health problems. In this paper, we introduce the protocol for the NIHR-funded SIPP (Safe inhalation pipe provision) project and discuss implications for impact. METHODS: The SIPP study will develop, implement and evaluate a crack smoking equipment and training intervention to be distributed through peer networks and specialist drug services in England. Study components comprise: (1) peer-network capacity building and co-production; (2) a pre- and post-intervention survey at intervention and non-equivalent control sites; (3) a mixed-method process evaluation; and (4) an economic evaluation. Participant eligibility criteria are use of crack within the past 28 days, with a survey sample of ~ 740 for each impact evaluation survey point and ~ 40 for qualitative process evaluation interviews. Our primary outcome measure is pipe sharing within the past 28 days, with secondary outcomes pertaining to use of homemade pipes, service engagement, injecting practice and acute health harms. ANTICIPATED IMPACT: SIPP aims to reduce crack use risk practices and associated health harms; including through increasing crack harm reduction awareness among service providers and peers. Implementation has only been possible with local police approvals. Our goal is to generate an evidence base to inform review of the legislation prohibiting crack pipe supply in the UK. This holds potential to transform harm reduction service provision and engagement nationally. CONCLUSION: People who smoke crack cocaine in England currently have little reason to engage with harm reduction and drug services. Little is known about this growing population. This study will provide insight into population characteristics, unmet need and the case for legislative reform. TRIAL REGISTRATION: ISRCTN12541454  https://doi.org/10.1186/ISRCTN12541454.

Substance use patterns, sociodemographics, and health profiles of harm reduction service recipients in Burlington, Vermont.

BACKGROUND: Understanding current substance use practices is critical to reduce and prevent overdose deaths among individuals at increased risk including persons who use and inject drugs. Because individuals participating in harm reduction and syringe service programs are actively using drugs and vary in treatment participation, information on their current drug use and preferred drugs provides a unique window into the drug use ecology of communities that can inform future intervention services and treatment provision. METHODS: Between March and June 2023, 150 participants in a harm reduction program in Burlington, Vermont completed a survey examining sociodemographics; treatment and medication for opioid use disorder (MOUD) status; substance use; injection information; overdose information; and mental health, medical, and health information. Descriptive analyses assessed overall findings. Comparisons between primary drug subgroups (stimulants, opioids, stimulants-opioids) of past-three-month drug use and treatment participation were analyzed using chi-square and Fisher's exact test. RESULTS: Most participants reported being unhoused or unstable housing (80.7%) and unemployed (64.0%) or on disability (21.3%). The drug with the greatest proportion of participants reporting past three-month use was crack cocaine (83.3%). Fentanyl use was reported by 69.3% of participants and xylazine by 38.0% of participants. High rates of stimulant use were reported across all participants independent of whether stimulants were a participant's primary drug. Fentanyl, heroin, and xylazine use was less common in the stimulants subgroup compared to opioid-containing subgroups (p < .001). Current- and past-year MOUD treatment was reported by 58.0% and 77.3% of participants. Emergency rooms were the most common past-year medical treatment location (48.7%; M = 2.72 visits). CONCLUSIONS: Findings indicate high rates of polysubstance use and the underrecognized effects of stimulant use among people who use drugs-including its notable and increasing role in drug-overdose deaths. Crack cocaine was the most used stimulant, a geographical difference from much of the US where methamphetamine is most common. With the increasing prevalence of fentanyl-adulterated stimulants and differences in opioid use observed between subgroups, these findings highlight the importance and necessity of harm reduction interventions (e.g., drug checking services, fentanyl test strips) and effective treatment for individuals using stimulants alongside MOUD treatment.

Making Harm Reduction More Accessible: Fentanyl Test Strip Awareness and Attitudes among Emergency Department Patients Who Use Drugs.

BACKGROUND: Fentanyl test strips (FTS) are a harm reduction method for people to test their drugs for fentanyl. Ideal points for FTS distribution have not been identified. Many people who use drugs have frequent contact with the Emergency Department (ED). We piloted FTS distribution in two urban hospital EDs. METHODS: Between June-December 2021 in Philadelphia, PA, patients with past 30-day drug use completed a survey about drug use, fentanyl attitudes, and FTS; then offered FTS and a brief training. Survey data were analyzed using SPSS for bivariate statistics. RESULTS: Patients (n = 135) were primarily White (68.1%) and male (72.6%). Participants regularly interacted with substance use (57.8%) and benefits coordination (49.6%) services. The most common drugs used were heroin/fentanyl (68.9%), crack cocaine (45.2%) and cannabis (40.0%). Most (98.5%) had heard of fentanyl though few (18.5%) had ever used FTS. Across most drug types, participants were concerned about fentanyl. All accepted FTS training and distribution. Few (9.6%) were somewhat or very concerned about having FTS if stopped by police and this number varied by race (7.6% of White people were somewhat or very concerned, compared to 12.8% of Black people). Most participants were already engaged in risk reduction practices. DISCUSSION: FTS are a widely desired harm reduction tool to facilitate informed decision-making, and non-harm reduction locations are potentially feasible and acceptable distribution sites. Given regular contact with EDs and social services across the sample, FTS should be offered at non-harm reduction locations that come into frequent contact with people who use drugs.

Correlates of Stimulant Use among People Who Use Heroin Undergoing Treatment in Out-Patient Facilities in France, 2010-2020.

Background: Polydrug use has been implicated in driving a "fourth wave" of the overdose crisis in North America, specifically through concurrent use of stimulants and opioids, especially fentanyl. In France, however, heroin has historically been and remains the easiest-to-access opioid, accounting for most drug treatment demand. Whether similar polydrug use is increasing in Western Europe remains understudied, despite severe health implications and potential inadequate public health responses.Methods: We take advantage of a nation-wide dataset containing information on all patients serviced in treatment centers in France from 2010 to 2020. We conduct Poisson regression to determine the main predictors of stimulant use among people who use heroin (PWUH) and opioids (PWUO) generally.Results: Heroin remains the primary opioid within drug treatment in France. A decreasing number of out-patients seeking treatment for heroin use has been accompanied by an increasing trend of stimulant use over time, most commonly with powder cocaine. Our results suggest a significant increase of crack cocaine use among the most vulnerable PWUH. Concurrent use of stimulants among PWUH was positively associated with use of alcohol, cannabis, unprescribed psychotropics and hallucinogens, and negatively with tobacco. Similar results were found for all in-treatment PWUO.Conclusions: Our results uncover heterogeneity in the profiles of PWUH that should be fully acknowledged to ensure better efficiency in substance use clinical practices and policy, while simultaneously drawing attention to trends in concurrent opioid-stimulant use outside North America. We advocate for an extension of the generalized risk framework and its implementation in prevention programs.

Overamped: Stimulant Use and HIV Pathogenesis.

PURPOSE OF REVIEW: In the era of HIV treatment as prevention (TasP), more clarity is needed regarding whether people with HIV who use stimulants (i.e., methamphetamine, powder cocaine, and crack cocaine) display elevated HIV viral load and greater immune dysregulation. RECENT FINDINGS: Although rates of viral suppression have improved in the TasP era, stimulant use was independently associated with elevated viral load in 23 of 28 studies included in our review. In the 12 studies examining other HIV disease markers, there was preliminary evidence for stimulant-associated alterations in gut-immune dysfunction and cellular immunity despite effective HIV treatment. Studies generally focused on documenting the direct associations of stimulant use with biomarkers of HIV pathogenesis without placing these in the context of social determinants of health. Stimulant use is a key barrier to optimizing the effectiveness of TasP. Elucidating the microbiome-gut-brain axis pathways whereby stimulants alter neuroimmune functioning could identify viable targets for pharmacotherapies for stimulant use disorders. Examining interpersonal, neighborhood, and structural determinants that could modify the associations of stimulant use with biomarkers of HIV pathogenesis is critical to guiding the development of comprehensive, multi-level interventions.

Does the Association Between Stimulant use and High Risk Sexual Behavior Vary by Injection Drug Use, Sexual Minority Status, or HIV Infection Status? A Meta-analysis.

There is strong evidence linking stimulant use, namely methamphetamine use, to sexual risk behavior among sexual minority men (SMM); we do not, however, have a good understanding of this relationship among other at-risk populations. In this study, we systematically reviewed associations between stimulant use (i.e., methamphetamine, crack cocaine, cocaine) and sexual risk behaviors among populations facing elevated risk of HIV transmission and acquisition (i.e., SMM, people who inject drugs (PWID), and people living with HIV/AIDS (PLWH)). Random-effects meta-analyses and sensitivity analyses that included crude and adjusted estimates separately were conducted to evaluate the impact of potential confounding variables. The results showed strong relationships between stimulant use and condomless sex, transactional sex, and multiple sexual partners. Results were broadly consistent when analyses were stratified by type of stimulant (methamphetamine, crack cocaine, and other stimulants) and risk group. Sensitivity analyses with confounding variables did not greatly impact results. The results indicate that stimulant use is associated with numerous sexual risk behaviors regardless of risk group, suggesting prevention efforts focused on reducing methamphetamine-related HIV risk should target a range of at-risk populations.

The utilization and delivery of safer smoking practices and services: a narrative synthesis of the literature.

BACKGROUND: Providing sterile drug smoking materials to people who use drugs can prevent the acquisition of infectious diseases and reduce overdose risk. However, there is a lack of understanding of how these practices are being implemented and received by people who use drugs globally. METHODS: A systematic review of safer smoking practices was conducted by searching PubMed, PsycInfo, Embase for relevant peer-reviewed, English-language publications from inception or the availability of online manuscripts through December 2022. RESULTS: Overall, 32 peer-reviewed papers from six countries were included. 30 studies exclusively included people who use drugs as participants (n = 11 people who use drugs; generally, n = 17 people who smoke drugs, n = 2 people who inject drugs). One study included program staff serving people who use drugs, and one study included staff and people who use drugs. Sharing smoking equipment (e.g., pipes) was reported in 25 studies. People who use drugs in several studies reported that pipe sharing occurred for multiple reasons, including wanting to accumulate crack resin and protect themselves from social harms, such as police harassment. Across studies, smoking drugs, as opposed to injecting drugs, were described as a crucial method to reduce the risk of overdose, disease acquisition, and societal harms such as police violence. Ten studies found that when people who use drugs were provided with safer smoking materials, they engaged in fewer risky drug use behaviors (e.g., pipe sharing, using broken pipes) and showed improved health outcomes. However, participants across 11 studies reported barriers to accessing safer smoking services. Solutions to overcoming safer smoking access barriers were described in 17 studies and included utilizing peer workers and providing safer smoking materials to those who asked. CONCLUSION: This global review found that safer smoking practices are essential forms of harm reduction. International policies must be amended to help increase access to these essential tools. Additional research is also needed to evaluate the efficacy of and access to safer smoking services, particularly in the U.S. and other similar countries, where such practices are being implemented but have not been empirically studied in the literature.

ADHD and addictive behavior in crack-cocaine users.

BACKGROUND: Crack consumption is a major public health issue in Martinique with a poor prognosis. A preliminary study has found a high prevalence of history of childhood ADHD (C-ADHD) in crack users. OBJECTIVE: To determine the prevalence of C-ADHD and adult ADHD (A-ADHD) in crack users and their potential associations with substance use behavior. METHODS: All consecutive patients consulting in the public academic hospital covering 376,000 inhabitants were included in the present study and received a comprehensive battery measuring addictive behavior, psychiatric and somatic comorbidities. C-ADHD groups and A-ADHD groups were defined with the Wender-Utah Rating Scale-25 and the Brown ADD Rating Scale, respectively. Impulsivity was evaluated with the Barratt Impulsiveness Scale (BIS-11). FINDINGS: In total, 111 participants were evaluated. Among them, 50 (45%) were classified in the C-ADHD group and 20 (18%) in the A-ADHD group. Compared to the patients without ADHD, those with ADHD were found to have higher impulsivity (C-ADHD: BIS total score 67.90 (10.1) vs. 63.28 (10.5), P=0.021, BIS attentional score 17.5 (3.6) vs. 15.3 (3.4), P=0.002, A-ADHD: BIS total score 75.1 (11.3) vs. 63.4 (9.2), P<0.001, BIS motor impulsivity 26.9 (5.3) vs. 22.6 (4.3), P<0.001, BIS attentional score 19.3 (3.3) vs. 15.6 (3.5), P<0.001, BIS planification 28.9 (5.7) vs. 25.10 (4.7), P=0.003). Fifty percent of A-ADHD patients were found with high impulsivity vs. 15% of patients without A-ADHD (P<0.001). However, ADHD was not associated with more severe addictive behavior or history of legal consequences. INTERPRETATION: ADHD prevalence is high in cocaine-crack users and associated with increased impulsivity. However, neither ADHD nor impulsivity explains addictive behaviors or legal consequences.

Crack cocaine use frequency is associated with HIV disease severity independent of antiretroviral therapy exposure: a prospective cohort study.

We sought to evaluate the effect of crack cocaine use frequency on HIV disease severity among HIV-positive people who use unregulated drugs (PWUD). We analyzed data from the ACCESS study, an open prospective cohort of HIV-positive PWUD including comprehensive HIV clinical monitoring in a setting with no-cost healthcare. Multivariable generalized linear mixed-effects models were used to estimate the independent effect of time-updated crack cocaine use frequency on HIV disease severity, adjusting for ART exposure and relevant confounders. In multivariable adjusted models, daily or greater frequency of crack cocaine use was significantly associated with higher VACS Index scores (ß = 0.8, 95% confidence interval: 0.1, 1.5) as compared to none. Our finding suggests that daily or greater frequency of crack cocaine use exacerbates HIV disease severity independent of ART exposure. The observed effect may reflect an underlying biological mechanism or other factors linked with crack cocaine use; further investigation is warranted.

Polysubstance use and adherence to antiretroviral treatment in the Miami Adult Studies on HIV (MASH) cohort.

Evidence for a relationship between polysubstance use, depression, and adherence to antiretroviral therapy (ART) is limited. The objectives of this study were to examine the associations of depression, illicit drug, and alcohol use with adherence to ART. People living with HIV (PLHIV) from the Miami Adult Studies on HIV cohort were asked about the number of doses of their ART medication missed to assess ART adherence. Harmful alcohol drinking was evaluated using the Alcohol Use Disorders Identification Test and illicit substance use assessed with self-report and urine screen. The Center for Epidemiologic Studies Depression Scale was used to assess depression symptoms. Of 391 PLHIV, 16.6% missed at least one dose (range:1-4) in the past four days. Cocaine/crack, opiate use, and depression were significantly independently associated with a greater mean number of doses missed. The mean number of doses missed was significantly greater among participants who used alcohol in combination with cocaine/crack, marijuana, and tobacco compared to non-users. In conclusion, polysubstance use increased the risk for poor ART adherence among PLHIV. The use of cocaine/crack or opiates individually and depressive symptoms also promote poor ART adherence. An integrated approach targeting substance disorders and depression may help achieve better ART adherence.

Validation of Brief Condom Use Attitudes Scales for Spanish-Speaking People Who Use Crack Cocaine in El Salvador.

People who use crack cocaine (PWUCC) are a population severely impacted by a concentrated epidemic of HIV. Behavioral interventions to prevent and treat HIV among PWUCC have been implemented around the world including in low- and middle-income countries which have been disproportionately affected by HIV. However, few studies have validated and assessed psychometric properties of measures on PWUCC, especially in transnational populations. Our sample was comprised of 1324 PWUCC, Spanish mono-lingual speakers, residing in the metropolitan area of San Salvador, El Salvador. Exploratory factor analysis and subsequent confirmatory factor analysis using statistical softwares SPSS and Amos were conducted on three abbreviated and translated condom use attitude measures (i.e., Condom Use Attitudes Scale-Spanish Short Form, Condom Use Social Norm-Spanish Short Form [CUSN-SSF], Condom Use Self-Efficacy-Spanish Short Form). Convergent validity was examined by computing bivariate correlations between the scales and condom use and sexually transmitted disease diagnosis. Results indicated that a two-factor, 8-item correlated model for the CUAS-SSF scale had an excellent fit and adequate reliability (α = .76). The confirmatory factor analysis for the 5-item CUSN-SSF scale indicated a satisfactory fit with 3 of 6 fit indices indicating adequate fit. Analysis of the two-factor 5-item CUSE-SSF scale indicated satisfactory fit and adequate reliability (α = .84). There were significant correlations between all measures and with self-reported condom use. Results indicate that these brief measures are reliable and valid and can be utilized to assess the effectiveness of HIV risk reduction interventions among Spanish-speaking PWUCC.

Histopathological and inflammatory response in multiple organs of rats exposed to crack.

The aim of this study was to investigate histopathological and inflammatory response in liver and kidney of rats after crack exposure. For this purpose, a total of 32 male Wistar rats were distributed into four groups: (G1) and (G2): received 18 mg/kg of body weight (b.w) of crack cocaine, but Group G2 remained 72 h without exposure after the experimental period (5 days). Experimental group 3 (G3): received 36 mg/kg of body weight (b.w) of crack cocaine. Control Group (CTRL): received only the vehicle (DMSO) administered by intraperitoneal (i.p) route for 5 days. The results showed that crack cocaine induced histopathological changes in liver and kidney. Immunohistochemistry data revealed that G2 group showed a higher immunoexpression of Ki-67 in hepatic and renal tissues. Regarding inflammation, the results showed that all groups exposed to crack cocaine decreased the expression of TNF-α, IL-6, and IL-10 in liver and kidney. In summary, our results showed that the subacute doses of crack cocaine used in this study had cytotoxic, and immunosuppressive effects in liver and kidney of rats, especially at 36 mg/kg dose. Since cellular death and inflammation participates in the multi-step process of chemical carcinogenesis, these data offer new insights into potential ways to understand the pathobiological mechanisms induced by crack cocaine in several tissues and organs.

Cumulative Effects of Adding a Small Group Intervention to Social Network Testing on HIV Testing Rates Among Crack Users in San Salvador, El Salvador.

The present study evaluates a combination prevention intervention for crack users in San Salvador, El Salvador that included social network HIV testing, community events and small group interventions. We examined the cumulative effects of the social network HIV testing and small group interventions on rates of HIV testing, beyond the increase that we saw with the introduction of the social network HIV testing intervention alone. HIV test data was converted into the number of daily tests and analyzed the immediate and overtime impact of small group interventions during and in the twelve weeks after the small group intervention. The addition of the small group interventions to the baseline of monthly HIV tests resulted in increased rates of testing lasting 7 days after the small group interventions suggesting a reinforcing effect of small group interventions on testing rates.

Drug and alcohol use among people living with HIV in care in the United States by geographic region.

Substance use in the U.S. varies by geographic region. Opioid prescribing practices and marijuana, heroin, and methamphetamine availability are evolving differently across regions. We examined self-reported substance use among people living with HIV (PLWH) in care at seven sites from 2017-2019 to understand current regional substance use patterns. We calculated the percentage and standardized percentage of PLWH reporting current drug use and at-risk and binge alcohol use by U.S. Census Bureau geographic region and examined associations in adjusted logistic regression analyses. Among 7,686 PLWH, marijuana use was the most prevalent drug (30%), followed by methamphetamine/crystal (8%), cocaine/crack (7%), and illicit opioids (3%). One-third reported binge alcohol use (32%). Differences in percent of current use by region were seen for marijuana (24-41%) and methamphetamine/crystal (2-15%), with more use in the West and Northeast, and binge alcohol use (26-40%). In adjusted analyses, PLWH in the Midwest were significantly less likely to use methamphetamine/crystal (aOR: 0.13;0.06-0.25) or illicit opioids (aOR:0.16;0.05-0.53), and PLWH in the Northeast were more likely to use cocaine/crack (aOR:1.59;1.16-2.17), compared to PLWH in the West. Understanding differences in substance use patterns in the current era, as policies continue to evolve, will enable more targeted interventions in clinical settings among PLWH.

Repeated crack cocaine administration alters panic-related responses and delta FosB immunoreactivity in panic-modulating brain regions.

Crack cocaine is the crystal form of cocaine, produced by adding sodium bicarbonate to cocaine base paste. Brazil is the largest consumer of crack cocaine in the world. Users of crack cocaine show important physiological and behavioral alterations, including neuropsychiatric symptoms, such as anxiety-related symptoms. Nevertheless, few pre-clinical studies have been previously performed to understand the neurobiological effects of crack cocaine. The purpose of the present study was to investigate effects of the subchronic treatment (5 days, IP) of rats with crack cocaine in an animal model of anxiety/panic, the elevated T-maze (ETM). The ETM model allows the measurement of two behavioral defensive responses, avoidance and escape, in clinical terms, respectively, associated to generalized anxiety and panic disorder, the two main psychiatric conditions that accompany substance use disorders. Immediately after the ETM model, animals were tested in an open field for locomotor activity assessment. Analysis of delta FosB protein immunoreactivity was used to map areas activated by crack cocaine exposure. Results showed that crack treatment selectively altered escape displayed by rats in the ETM test, inducing either a panicolytic (18 mg/kg IP) or a panicogenic-like effect (25 and 36 mg/kg IP). These effects were followed by the altered functioning of panic-modulating brain regions, i.e., the periaqueductal gray and the dorsal region and lateral wings of the dorsal raphe nucleus. Treatment with 36 mg/kg of crack cocaine also increased locomotor activity. These are the first observations performed with crack cocaine in a rodent model of anxiety/panic and contribute to a better understanding of the behavioral and neurobiological effects of crack cocaine.

Factors associated with crack-cocaine early initiation: a Brazilian multicenter study.

BACKGROUND: Crack-cocaine dependence is a serious public health issue, related to several psychiatric and psychosocial problems. Crack-cocaine users are usually embedded in a context of great social vulnerability, often associated with violence, poverty, family conflict and easy and early access to alcohol, tobacco and other drugs. METHODS: This cross-sectional study enrolled a consecutive sample of 577 patients admitted to 20 therapeutic communities located in Southern Brazil, between September 2012 and September 2013. A structured interview assessed life-time exposure to risk and protective factors for drug use, such as parental monitoring in childhood, deviant behaviors and peer pressure. RESULTS: Presence of family conflict (p = 0.002), maltreatment (p = 0.016), and deviant behavior prior to age 15 in a bivariate analysis predicted an earlier age of crack-cocaine initiation, whereas adolescents experiencing parental monitoring during adolescence started use later (p < 0.001). In the multivariate model, perceptions related to ease of access of illicit drugs (marijuana: p = 0.028, 95% CI = - 3.81, - 0.22; crack-cocaine: p < 0.001, 95% CI = - 7.40, - 4.90), and deviant behavior (threatening someone with a gun: p = 0.028, 95% CI = - 2.57, - 0.14) remained independent predictors of early age of crack-cocaine initiation. CONCLUSIONS: Early onset of crack-cocaine use seems to be associated with exposure to family conflict, easy access to drugs and deviant behavior. Treatment and preventive programs should take these factors into account when designing and implementing community interventions.

Estimates of the Incidence of Crack Cocaine Use in Those Likely to Attend Treatment in the English Population, 2005-2018.

BACKGROUND: Public health bodies in the UK, and elsewhere, have expressed concern over the wider social and economic impact of crack cocaine use on society. OBJECTIVE: The aim of the study was to use English substance misuse treatment data to estimate the incidence of crack cocaine use in the population who are expected to present to treatment with crack cocaine as the primary substance. METHOD: Known year of first crack-related treatment demand and age of first use of crack were combined to provide the distribution of lag to treatment for each year of onset. The resulting combined lag distribution was used to estimate the proportion of incident crack cocaine users who will have presented in a given year and, from that, the total number who will have started in that year. RESULTS: Our estimates identified an approximate doubling in incidence between 2012 and 2016, following a decrease up to 2012. CONCLUSION: This represents an increase in treatment demand that is likely to continue for a number of years.