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.

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.

The Interactions Between Vulnerabilities for HIV and Syphilis among Cisgender and Transgender People Who Use Drugs.

In Brazil, transgender people are most affected by HIV, and crack cocaine addiction may contribute to social vulnerability and exposure to sexual and violence-related risks. This cross-sectional study comprised 2393 individuals seeking addiction treatment, consisting of 43 trans women, 1995 cisgender men, and 355 cisgender women. Records of rapid test results for HIV and syphilis and screening responses of trans women were compared to both cisgender groups using a logistic regression model to identify associated risk factors. HIV prevalence was higher in the transgender group (39.5%) than in cis women and men (5.9% and 3.6%, respectively). Our study showed an eightfold higher chance of a positive HIV test among transgender individuals who used drugs (OR: 8.79, p < .01, 95% CI: 3.90-19.78) compared to cisgender people who used drugs. A lifetime history of syphilis infection was more common in transgender people (60.0%) and cis women (32.8%) than in cis men (9.5%). Active syphilis was also more common in the transgender population (OR: 5.46, p < .01, 95% CI: 2.63 11.32). In our sample, 44.2% of transgender individuals had a history of at least one suicide attempt in their lifetime. Our results showed that transgender women were at higher risk of crack cocaine use (OR: 5.51, p < .01, 95% CI: 2.16-14.06) than cisgender men and women. The study showed that trans women had a higher prevalence of syphilis and HIV, and a greater chance of being homeless. The synergy of these vulnerabilities may have led to our findings of high psychotic symptoms and a history of suicide attempts in transgender individuals.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Not all screens are created equal: examination of surface features and other physical properties of commonly used screen materials for smoking drugs.

BACKGROUND: Brass screens are considered an essential part of the safer drug smoking/inhalation supplies and are widely distributed by harm reduction programs in Canada. However, the use of commercially available steel wools as screens for smoking crack cocaine remains a common practice among people who smoke drugs in Canada. Use of these steel wool materials is associated with different adverse effects on health. This study aims to determine what changes folding and heating have on several filter materials, including brass screens and commercially available steel wool products, and examine the implications of these changes on health of people who smoke drugs. METHODS: This study investigated the microscopic differences, studied by optical and scanning electron microscopy, between four screen and four steel wool filter materials used in a simulated drug consumption process. New materials were manipulated, compacted into its own Pyrex® straight stem using a push stick and then heated with a butane lighter simulating a common method in preparing drugs for consumption. The materials were studied in the as-received (new), as-pressed (compressed and inserted into the stem tube but without heating) and as-heated (compressed and inserted into the stem tube and heated with a butane lighter) conditions. RESULTS: The steel wool materials with the smallest wire thicknesses were found to be the easiest to prepare for pipe use, but degrade significantly during shaping and heating, making them wholly unsuitable as a safe filter material. In contrast the brass and stainless steel screen materials remain mostly unchanged by the simulated drug consumption process. After the stainless steel pellet screen, the Brass Impact 2.0 screen material had the best characteristics of the materials tested due to its mesh wire diameter, pitch, alloy choice and its pre-strained state. CONCLUSION: Commonly used steel wool alternatives degrade during the handling and stem insertion, and heating the screens in the stem. Debris is generated by wool deformation on insertion and after heating that easily separates from the screen and can be inhaled during drug consumption. The brass and stainless steel screen materials are safer to use as they remain mostly stable during the simulated drug consumption process.

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.

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.

Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

OBJECTIVE: The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD. METHODS: Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively. RESULTS: Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score. CONCLUSION: Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.

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.

Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner.

Crack cocaine users are simultaneously exposed to volatilized cocaine and to its main pyrolysis product, anhydroecgonine methyl ester (AEME). Although the neurotoxic effects of cocaine have been extensively studied, little is known about AEME or its combination. We investigated cell death processes using rat primary hippocampal cells exposed to cocaine (2 mM), AEME (1 mM) and their combination (C + A), after 1, 3, 6 and 12 h. Cocaine increased LC3 I after 6 h and LC3 II after 12 h, but reduced the percentage of cells with acid vesicles, suggesting failure in the autophagic flux, which activated the extrinsic apoptotic pathway after 12 h. AEME neurotoxicity did not involve the autophagic process; rather, it activated caspase-9 after 6 h and caspase-8 after 12 h leading to a high percentage of cells in early apoptosis. C + A progressively reduced the percentage of undamaged cells, starting after 3 h; it activated both apoptotic pathways after 6 h, and was more neurotoxic than cocaine and AEME alone. Also, C + A increased the phosphorylation of p62 after 12 h, but there was little difference in LC3 I or II, and a small percentage of cells with acid vesicles at all time points investigated. In summary, the present study provides new evidence for the neurotoxic mechanism and timing response of each substance alone and in combination, indicating that AEME is more than just a biological marker for crack cocaine consumption, as it may intensify and hasten cocaine neurotoxicity.

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.

Oral HPV among people who use crack-cocaine: prevalence, genotypes, risk factors, and key interventions in a remote Northern Brazilian region.

OBJECTIVES: This study estimated the prevalence, genotype distribution, and the factors associated with oral human papillomavirus (HPV) in people who use crack-cocaine (PWUCC) in a remote Brazilian region. MATERIALS AND METHODS: This cross-sectional study used community-based snowball sampling methods for participant recruitment. Socio-demographic, economic, drug use, and health-related information was collected from 278 PWUCC in the cities of Bragança and Capanema in northern Brazil. HPV diagnosis and genotyping were performed by a real-time polymerase chain reaction. Logistic regression identified the factors independently associated with oral HPV. RESULTS: In total, 111 (39.9%) PWUCC had HPV DNA. Several genotypes were identified, some of them with high oncogenic potential. Crack-cocaine use ≥40 months, unprotected sex, more than 10 sexual partners in the last 12 months, oral sex, exchange of sex for money or illicit drugs, oral mucosa lesions, not having access to public health services, and the absence of vaccination against HPV was all associated with HPV DNA. CONCLUSIONS: This study identified important epidemiological characteristics of oral HPV infection among PWUCC-a highly marginalized risk population-underlining the high prevalence of oral HPV with oncogenic potential and the urgent need for control and prevention measures, especially vaccination against this virus. CLINICAL RELEVANCE: It is necessary to understand the prevalence and risk factors of oral HPV in risk populations as people who use crack-cocaine.

Social support networks of users of crack cocaine and the role of a Brazilian health program for people living on the street: A qualitative study.

This cross-sectional qualitative study analyzed characteristics of social support for users of crack cocaine and the role of "Consultório na Rua" (CR), or "Office in the Street," a Brazilian program for people living on the street. Data were collected using 1) ethnographic field observations during the delivery of services from this program, 2) in-depth interviews with 17 users of crack cocaine, and 3) a focus group with professionals from CR. To analyze data, we used content analysis and analytical categories based on Social Network Analysis (SNA) theoretical statements. Results showed that family, peers, community members, and professionals from CR were the main social support providers. Participants mentioned receiving material, informational, and emotional support from CR members. It was observed that CR had a welcoming and inclusive approach, but CR team members identified challenges related to stigma directed toward people who use substances and live on the street. CR assumed a central role in the health and social assistance of users of crack cocaine living on the street, providing an important link to healthcare and social services. However, initiatives related to motivation to receive mental health services, treatment, or social reintegration were not observed in conjunction with this program.

Molecular and epidemiological aspects of hepatitis C virus infection among crack cocaine users.

The aim is to investigate the prevalence, risk factors, and hepatitis C virus (HCV) genotypes/subtypes among crack users in-treatment in Central Brazil. A cross-sectional survey in which 600 in-treatment crack users were interviewed and tested for anti-HCV Ab by enzyme-linked immunosorbent assay was conducted between August 2012 and April 2013. Anti-HCV-positive samples were also submitted for HCV RNA detection by polymerase chain reaction. Positive HCV RNA samples were genotyped by direct sequencing analysis of the NS5B region of the viral genome, followed by phylogenetic analysis. Of the total, 3.7% (95.0% CI, 2.4%-5.6%) were anti-HCV positive. Age over 40 years and history of injecting drugs were risk factors for HCV, while snorting cocaine was a protector variable. HCV RNA was detected in 14 of 22 anti-HCV-positive samples, and the genotypes 1 (n = 10) and 3 (n = 2), subtypes 1a (n = 7), 1b (n = 3), and 3a (n = 2) were identified. The HCV prevalence found among crack users is almost threefold that observed in the general population in Brazil supporting that this population is at higher risk for HCV. The findings of cocaine insufflation as a protective behavior for HCV infection in this population should be explored.

Addressing overdose risk among unstably housed women in San Francisco, California: an examination of potential fentanyl contamination of multiple substances.

BACKGROUND: Numerous reports have led to concerns that fentanyl is added to many street drugs as an adulterant, including to stimulants like cocaine and methamphetamine, and could increase risks for negative health outcomes. METHODS: We collected information regarding recent substance use through self-report and urine toxicology (confirmed with mass spectrometry) once a month for up to 6 monthly study visits from a probability sample of 245 women in San Francisco with a history of housing instability (2016-2019). We compared the presence of fentanyl metabolites with (1) the presence of metabolites for other substances and (2) self-reported past week substance use. RESULTS: Out of 1050 study visits, fentanyl metabolites were detected 35 times (i.e., at 3% of all study visits and among 19/245, or 8% of all women). In most but not all (91%, or 32/35) of these detected cases, heroin or opioid medication use was self-reported. Among women who reported cocaine or methamphetamine use, but did not use heroin or opioid medication, fentanyl was detected in only 1 of 349 cases (0.3%). In adjusted logistic regression, the presence of fentanyl metabolites was independently associated with (1) presence of opiate, heroin, and benzodiazepine metabolites, and (2) self-reported past week use of heroin and opioid medications. Fentanyl metabolite detection was not independently associated with cocaine or methamphetamine use. CONCLUSIONS: The presence of fentanyl metabolites in this population was almost entirely among women who also reported using heroin or opioid pills. These data do not support the hypothesis that fentanyl is being routinely added to stimulants as an adulterant on a large scale in this region.

Navigating environmental constraints to injection preparation: the use of saliva and other alternatives to sterile water among unstably housed PWID in London.

BACKGROUND: The United Kingdom is experiencing an increase in drug-related deaths and serious bacterial infections among its most vulnerable citizens. Cuts to essential services, coupled with a growing homeless population, create a challenging environment to tackle this public health crisis. In this paper, we highlight an underexplored environmental constraint faced by people living and injecting drugs on the streets. Access to water for injection is restricted in the UK, due to legislative and financial barriers. Austerity measures, such as public toilet closures, further restrict the ability of people made homeless to access clean water and protect themselves from health harms. METHODS: We generated questionnaire (n = 455) and in-depth qualitative interview (n = 32) data with people who inject drugs in London for the Care and Prevent study. Participants provided detail on their life history; drug use, injecting and living environments; health conditions and care seeking practices. FINDINGS: A high proportion of the survey sample reported lifetime history of street homelessness (78%), bacterial infections (65%) and related hospitalisation (30%). Qualitative accounts highlight unsafe, potentially dangerous, injection practices in semi-public spaces. Multiple constraints to sourcing sterile water for injection preparation were reported. Alternatives to sterile water included puddle water, toilet cistern water, whisky, cola soda and saliva. Participants who injected heroin and crack cocaine together unanimously reported adding water at two stages during injection preparation: first, adding water as a vehicle for heroin (which was then heated); second, adding cold water to the heroin mixture prior to adding the crack cocaine. This new finding of a stage addition of solvent may represent an additional risk of infection. CONCLUSION: Currently, harm reduction equipment and resources for safe injecting are not meeting the needs of people who inject drugs who are street homeless or unstably housed. Preparation of injections with non-sterile water sources could precipitate bacterial and fungal infections, particularly when used without the application of heat. It is crucial that water for injection, also skin cleaning, is made available for the unstably housed and that harm reduction messaging is tailored to speak to the everyday realities of people who prepare and inject drugs in public spaces.

Concurrent Use of Alcohol and Crack Cocaine is Associated with High Levels of Anger and Liability to Aggression.

Objective: To evaluate aggressiveness in individuals receiving treatment for alcohol and crack cocaine use, both alone and in combination with one another, in order to compare them to control subjects with no history of drug problems, using the State-Trait Anger Expression Inventory. Method: The sample consisted of 67 men aged 18-65 years, divided into four groups: alcohol (n = 13); crack cocaine (n = 25); crack cocaine + alcohol (n = 16) and controls (n = 13). Participants completed the following instruments: socioeconomic questionnaire, the Wechsler Abbreviated Scale of Intelligence and the State-Trait Anger Expression Inventory. Results: Individuals with alcohol dependence alone, or comorbid with crack cocaine dependence, showed elevated levels of aggression and anger, though these varied according to the drug of abuse. Concurrent users of alcohol and crack cocaine had the highest levels of aggression, followed by isolated alcohol users, suggesting an association between alcohol consumption and aggression. Conclusion: The present findings suggest that alcohol and aggression levels may be associated with violent behavior. Concurrent use of alcohol and crack cocaine was related to higher levels of aggression, which may be associated with more severe alterations in behavior and impulse control.

Correlates of Self-Reported Cotton Fever Experience among People Who Inject Opioids.

Background: Cotton fever is a febrile syndrome occurring after intravenous drug injection. Although its clinical presentation is well described in the literature, data regarding prevention is lacking. We aimed to assess proportion and correlates of cotton fever experience among people who inject opioids. Methods: We performed a cross-sectional study using data from the community-based survey PrebupIV conducted in France in 2015 among 557 people who regularly injected opioids. Self-reported sociodemographic data, together with data on substance use, injecting practices and occurrence of cotton fever were all collected through face-to-face (n = 398) or online (n = 159) questionnaires. Factors associated with cotton fever experience were assessed using logistic regression model. Results: Over half of the participants (54%) reported cotton fever experience. In the multivariable logistic regression, crack cocaine injection (adjusted Odds Ratio (aOR) = 1.96, 95% Confidence Interval (CI) = 1.03-3.63), longer duration of opioid use (for 1 year of use: aOR = 1.05, 95%CI = 1.02-1.09), and filtering mainly with cotton filters (compared with membrane filters, aOR = 1.86, 95%CI = 1.24-2.78) were all associated with cotton fever experience. Conclusions: Our findings highlight that cotton fever is a frequent complication of injecting drug use. Avoiding the use and reuse of cotton balls to filter injected solutions, and promoting membrane filters use could reduce the risk of the condition occurring.