Impact of a Community Empowerment Intervention on Sexually Transmitted Infections Among Female Sex Workers in Baltimore, Maryland.

BACKGROUND: Female sex workers ( FSWs) are vulnerable to a number of health issues, but often delay seeking health care due to structural barriers. Multiservice drop-in centers have been shown to increase FSW access to health services globally, but their impact on FSW in the United States is lacking. This study seeks to evaluate the effect of a community-level empowerment intervention (the multiservice drop-in SPARC center) on cumulative sexually transmitted infections (STIs) among FSW in a city in the United States. METHODS: Between September 2017 and January 2019, 385 FSWs were recruited in Baltimore. Participants from areas served by SPARC were recruited to the intervention; other areas of Baltimore were the control. Follow-up occurred at 6, 12, and 18 months. The primary outcome is cumulative STI (ie, positive gonorrhea or chlamydia test at any follow-up). We tested effect modification by condomless sex with paying clients reported at baseline. Logistic regressions with propensity score weighting were used to estimate intervention effect, accounting for loss to follow-up, with bootstrap confidence intervals. RESULTS: Participants completed 713 follow-up study visits (73%, 70%, 64% retention at 6, 12, and 18 months, respectively). Baseline STI prevalence was 28% and cumulative STI prevalence across follow-ups was 26%; these both did not differ between control and intervention communities in bivariate analyses. After adjusting for covariates, FSW in the intervention had a borderline-significant decrease in odds of cumulative STI compared with control (odds ratio, 0.61, P = 0.09 ) . There was evidence of effect modification by baseline condomless sex, such that FSW in the intervention who reported condomless sex had lower odds of cumulative STI compared with FSW in the control community who also reported baseline condomless sex (odds ratio, 0.29; P = 0.04). CONCLUSIONS: Results demonstrate the value of a low-barrier, multiservice model on reducing STIs among the highest-risk FSW.Clinical Trial Number: NCT04413591.

A study protocol to explore and implement community-based point-of-care COVID-19 testing for women who use drugs in Baltimore, Maryland: The CARE study.

Women who use drugs (WWUD) experience structural vulnerabilities (e.g., housing, food insecurities) and comorbidities that elevate their susceptibility to more severe COVID-19 symptoms or fatality compared to similarly-aged women who do not use illicit drugs. Testing is a cornerstone of effective COVID prevention, however, entrenched barriers to healthcare utilization means that WWUD may have diminished accessing to COVID testing. The CARE (COVID Action Research Engagement) study first examines predisposing and enabling factors that predict COVID testing uptake over six months (baseline, 3-, and 6-month follow-up) among a cohort of WWUD (N = 250) in Baltimore, Maryland, providing a nuanced and holistic understanding of how to meaningfully engage WWUD in COVID testing. Then, point-of-care COVID testing will be implemented on a mobile outreach van affiliated with a local community-based organization primarily serving WWUD; anonymous surveys of mobile outreach guests (N = 100) will assess feasibility and acceptability of this integrated testing. The study is grounded in the Behavioral Model for Vulnerable Populations and the Theoretical Framework of Acceptability. We hypothesize that point-of-care COVID testing integrated into a low-barrier harm reduction service, such as a mobile outreach program, will be an enabling environment for COVID testing uptake in part by reducing structural impediments to testing and will be highly feasible and acceptable to participants. Strengths, limitations, and plans for results dissemination are discussed.

High acceptability of HIV self-testing in a randomized trial among transgender women and men who have sex with men, Myanmar.

HIV self-testing (HIVST) shows promise to improve HIV diagnosis among those seeking privacy and anonymity in HIV testing. This may include sexual and gender diverse populations, who experience disproportionately high burdens of stigma and HIV globally. To inform potential scale-up of HIVST in Myanmar, we implemented a community-led, mixed-methods randomized trial in Yangon. Adult trans-feminine individuals and cisgender men who have sex with men were recruited via respondent-driven sampling. Participants (N = 577) completed a baseline survey and were randomized to community-based HIV testing services (HTS) or HIVST. One-third of participants reported lifetime HIV testing. Over half (59.4%) returned for a second study visit to report their test result and test acceptability, which was lower among HTS-assigned participants compared to those assigned to HIVST (55.6% vs. 63.1%; p = 0.096). Participants reported that both HIVST and HTS were easy to access, test, and interpret/understand the results of their HIV test. Ninety percent of HTS-assigned participants indicated they would test regularly if they could access HIVST. Qualitative participants (N = 20) described that the convenience and privacy afforded by HIVST may increase the availability and coverage of testing. Taken together, these results suggest HIVST is an acceptable, low-barrier complement to community-based HTS for key populations in Myanmar.

The role of local business employees and community members in the HIV risk environment of female sex workers in an urban setting: associations between negative interactions and inconsistent condom use.

BACKGROUND: The role of business employees and community members in the HIV risk environment of female sex workers (FSW) is underexplored, despite sex work often located in commercial and residential urban areas. We explored the effect of negative interactions between business employees and community members on inconsistent condom use with clients of female sex workers. METHODS: This study uses baseline data from the EMERALD study, a community empowerment intervention with FSW. We recruited a sample of 361 FSW in Baltimore, Maryland using targeted sampling techniques in ten zones characterized by high rates of sex work, located throughout the city. Participants were recruited between September 2017 and January 2019 and completed a survey, HIV rapid testing, and self-administered gonorrhea and chlamydia testing. The outcome, inconsistent condom use, was defined as not reporting "always" using condoms with paying clients. Poisson regressions with robust variance were used to model the effect of business employee and/or community member interactions on inconsistent condom use. RESULTS: Over half (54%) the sample was between 18 and 40 years old, 44% Black or another race, and experienced a range of structural vulnerabilities such as housing instability and food insecurity. Forty-four percent of the sample reported inconsistent condom use with clients. FSW reported being reported to the police weekly or daily for selling drugs (14% by employees, 17% by community), for selling sex (19% by employees, 21% by community), and experiencing weekly or daily verbal or physical threats (18% by employees, 24% by community). In multivariable models, being reported to the police for selling sex weekly or daily by community members (vs. never, aRR = 1.42, 95% CI = 1.08, 1.86) and business owners (vs. never, aRR = 1.36, 95% CI = 1.05, 1.76) increased risk of inconsistent condom use, as did monthly verbal or physical threats by community members (vs. never, aRR = 1.43, 95% CI = 1.08, 1.91). CONCLUSIONS: Results show that both actors play important roles in FSWs' HIV risk environment. Businesses and community members are important targets for holistic HIV prevention interventions among FSW in communities where they coexist in close proximity.

The EMERALD (Enabling Mobilization, Empowerment, Risk Reduction, and Lasting Dignity) Study: Protocol for the Design, Implementation, and Evaluation of a Community-Based Combination HIV Prevention Intervention for Female Sex Workers in Baltimore, Maryland.

BACKGROUND: Cisgender female sex workers (FSWs) experience high rates of HIV and sexually transmitted infections (STIs), including chlamydia and gonorrhea. Community empowerment-based responses to the risk environment of FSWs have been associated with significant reductions in HIV and STI risk and associated risk behaviors; however, evaluations of US-based interventions targeting FSWs are limited. OBJECTIVE: The objective of this study is to describe the design, implementation, and planned evaluation strategy of an ongoing comprehensive community-level intervention in Baltimore City, Maryland, which aims to improve HIV and STI risk and cumulative incidence among FSWs. The two intervention components are the SPARC (Sex Workers Promoting Action, Risk Reduction, and Community Mobilization) drop-in center and the accompanying comprehensive mobile outreach program. The mission of SPARC is to provide low-barrier harm reduction services to FSWs, with a special focus on women who sell sex and use drugs. Services are provided through a harm reduction framework and include reproductive health and sexual health care; medication-assisted treatment; legal aid; counseling; showers, lockers, and laundry; and the distribution of harm reduction tools, including naloxone and sterile drug use supplies (eg, cookers, cotton, syringes, and pipes). METHODS: The SPARC intervention is being evaluated through the EMERALD (Enabling Mobilization, Empowerment, Risk Reduction, and Lasting Dignity) study, which consists of a prospective 2-group comparative nonrandomized trial (n=385), a cross-sectional survey (n=100), and in-depth interviews assessing SPARC implementation (n=45). Participants enrolled in the nonrandomized trial completed a survey and HIV and STI testing at 4 intervals (baseline and 6, 12, and 18 months). Participants recruited from predefined areas closest to SPARC comprised the intervention group, and participants from all other areas of Baltimore were included in the control group. RESULTS: We hypothesize that addressing structural drivers and more immediate medical needs, in combination with peer outreach, will improve the HIV and STI risk environment, leading to community empowerment, and reduce the HIV and STI cumulative incidence and behavioral risks of FSWs. Data collection is ongoing. A baseline description of the cohort is presented. CONCLUSIONS: In the United States, structural interventions aimed at reducing HIV and STIs among FSWs are scarce; to our knowledge, this is the first intervention of its kind in the United States. The results of the EMERALD study can be used to inform the development of future interventions targeting FSWs and other at-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04413591; https://clinicaltrials.gov/ct2/show/NCT04413591. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23412.

Structural and Environmental Influences Increase the Risk of Sexually Transmitted Infection in a Sample of Female Sex Workers.

BACKGROUND: Female sex workers (FSWs) have elevated rates of sexually transmitted infections (STIs) including HIV, yet few studies in the United States have characterized the STI burden in this population. METHODS: Data were derived from the EMERALD study, a structural community-based intervention with FSWs in Baltimore, MD. Participants (n = 385) were recruited through targeted sampling on a mobile van. Prevalent positive chlamydia or gonorrhea infections were determined by biological samples. Multivariable logistic regressions modeled correlates of confirmed positive STI (gonorrhea or chlamydia). RESULTS: Confirmed STI positive prevalence was 28%, 15% chlamydia and 18% gonorrhea. Approximately two-thirds of the sample (64%) was younger than 40 years, one-third (36%) were Black, and 10% entered sex work in the past year. The sample was characterized by high levels of structural vulnerabilities (e.g., housing instability and food insecurity) and illicit substance use. Female sex workers were more likely to have a positive STI if they had financial dependent(s) (P = 0.04), experienced food insecurity at least weekly (P = 0.01), entered sex work in the past year (P = 0.002), and had 6 or more clients in the past week (P = 0.01). Female sex workers were less likely to have a positive STI test result if they were 40 years or older compared with FSW 18 to 29 years old (P = 0.02), and marginally (P = 0.08) less likely with high (vs. low) social cohesion. CONCLUSIONS: More than a quarter of FSWs had confirmed chlamydia or gonorrhea. In addition to STI risks at the individual level, STIs are driven by structural vulnerabilities. Results point to a number of salient factors to be targeted in STI prevention among FSWs.

"We are not gays don't tell me those things": engaging 'hidden' men who have sex with men and transgender women in HIV prevention in Myanmar.

BACKGROUND: In Myanmar, HIV is concentrated among key populations, yet less than half of the estimated 250,000 men who have sex with men (MSM) and transgender women (TW) report recent HIV testing. As many as 50% of MSM and TW may conceal their same-sex preferences and behaviors, yet little is known about the barriers faced by those who are locally regarded as 'hidden' - that is, MSM who do not disclose same-sex preferences and/or identify as gay. This study explored specific barriers to accessing HIV testing and other prevention services among 'hidden' MSM to inform appropriate models of service delivery. METHODS: In-depth interviews with MSM (n = 12) and TW (n = 13) and focus group discussions (FGD) with MSM and TW community members, leaders and key informants (n = 35) were undertaken in Yangon during June - September 2015. Participants were recruited by word-of-mouth by trained peer data collectors. Responses to questions from semi-structured guides were transcribed and coded using Atlas Ti. Codes were based on key domains in the guides and applied to transcripts to identify and analyze emerging themes. RESULTS: Fear of stigma and discrimination and the need to meet gender expectations were key reasons for non-disclosure of same-sex preferences and behaviors; this typically manifested as avoidance of other MSM and settings in which sexual identity might be implicated. These concerns influenced preference and interaction with HIV services, with many avoiding MSM-specific services or eschewing HIV testing services entirely. The difficulties of engaging hidden MSM in HIV prevention was strongly corroborated by service providers. CONCLUSION: Hidden MSM face multiple barriers to HIV testing and prevention. Strategies cognizant of concerns for anonymity and privacy, such as One-Stop Shop services and online-based health promotion, can discretely provide services appropriate for hidden MSM. Enhanced capacity of peer-service providers and mainstream health staff to identify and respond to the psychosocial challenges reported by hidden MSM in this study may further encourage service engagement. Overarching strategies to strengthen the enabling environment, such as legal reform and LGBTI community mobilisation, can lessen stigma and discrimination and increase hidden MSM's comfort and willingness to discuss same-sex behavior and access appropriate services.

Qualitative accounts from Syrian health professionals regarding violations of the right to health, including the use of chemical weapons, in opposition-held Syria.

OBJECTIVES: To explore the impact of the conflict, including the use of chemical weapons, in Syria on healthcare through the experiences of health providers using a public health and human rights lens. DESIGN: A qualitative study using semi-structured interviews conducted in-person or over Skype using a thematic analysis approach. SETTING: Interviews were conducted with Syrian health workers operating in opposition-held Syria in cooperation with a medical relief organisation in Gaziantep, Turkey. PARTICIPANTS: We examined data from 29 semi-structured in-depth interviews with a sample of health professionals with current or recent work-related experience in opposition-controlled areas of Syria, including respondents to chemical attacks. RESULTS: Findings highlight the health worker experience of attacks on health infrastructure and services in Syria and consequences in terms of access and scarcity in availability of essential medicines and equipment. Quality of services is explored through physicians' accounts of the knock-on effect of shortages of equipment, supplies and personnel on the right to health and its ethical implications. Health workers themselves were found to be operating under extreme conditions, in particular responding to the most recent chemical attacks that occurred in 2017, with implications for their own health and mental well-being. CONCLUSIONS: The study provides unique insight into the impact war has had on Syrian's right to health through the accounts of a sample of Syrian health professionals, with continuing relevance to the current conflict and professional issues facing health workers in conflict settings.

Determining the scope of attacks on health in four governorates of Syria in 2016: Results of a field surveillance program.

BACKGROUND: Violent attacks on and interferences with hospitals, ambulances, health workers, and patients during conflict destroy vital health services during a time when they are most needed and undermine the long-term capacity of the health system. In Syria, such attacks have been frequent and intense and represent grave violations of the Geneva Conventions, but the number reported has varied considerably. A systematic mechanism to document these attacks could assist in designing more protection strategies and play a critical role in influencing policy, promoting justice, and addressing the health needs of the population. METHODS AND FINDINGS: We developed a mobile data collection questionnaire to collect data on incidents of attacks on healthcare directly from the field. Data collectors from the Syrian American Medical Society (SAMS), using the tool or a text messaging system, recorded information on incidents across four of Syria's northern governorates (Aleppo, Idleb, Hama, and Homs) from January 1, 2016, to December 31, 2016. SAMS recorded a total of 200 attacks on healthcare in 2016, 102 of them using the mobile data collection tool. Direct attacks on health facilities comprised the majority of attacks recorded (88.0%; n = 176). One hundred and twelve healthcare staff and 185 patients were killed in these incidents. Thirty-five percent of the facilities were attacked more than once over the data collection period; hospitals were significantly more likely to be attacked more than once compared to clinics and other types of healthcare facilities. Aerial bombs were used in the overwhelming majority of cases (91.5%). We also compared the SAMS data to a separate database developed by Physicians for Human Rights (PHR) based on media reports and matched the incidents to compare the results from the two methods (this analysis was limited to incidents at health facilities). Among 90 relevant incidents verified by PHR and 177 by SAMS, there were 60 that could be matched to each other, highlighting the differences in results from the two methods. This study is limited by the complexities of data collection in a conflict setting, only partial use of the standardized reporting tool, and the fact that limited accessibility of some health facilities and workers and may be biased towards the reporting of attacks on larger or more visible health facilities. CONCLUSIONS: The use of field data collectors and use of consistent definitions can play an important role in the tracking incidents of attacks on health services. A mobile systematic data collection tool can complement other methods for tracking incidents of attacks on healthcare and ensure the collection of detailed information about each attack that may assist in better advocacy, programs, and accountability but can be practically challenging. Comparing attacks between SAMS and PHR suggests that there may have been significantly more attacks than previously captured by any one methodology. This scale of attacks suggests that targeting of healthcare in Syria is systematic and highlights the failure of condemnation by the international community and medical groups working in Syria of such attacks to stop them.

The Parasol Protocol: An Implementation Science Study of HIV Continuum of Care Interventions for Gay Men and Transgender Women in Burma/Myanmar.

BACKGROUND: Efforts to improve HIV diagnosis and antiretroviral therapy (ART) initiation among people living with HIV and reduce onward transmission of HIV rely on innovative interventions along multiple steps of the HIV care continuum. These innovative methods are particularly important for key populations, including men who have sex with men (MSM) and transgender women (TW). The HIV epidemic in Myanmar is concentrated among key populations, and national efforts now focus on reducing stigma and improving engagement of MSM and TW in HIV prevention and care. OBJECTIVE: This study aims to test the use of several innovations to address losses in the HIV care continuum: (1) use of respondent-driven sampling (RDS) to reach and engage MSM and TW in HIV testing, (2) HIV self-testing (HIVST) to increase HIV testing uptake and aid early diagnosis of infection, (3) community-based CD4 point-of-care (POC) technology to rapidly stage HIV disease for those who are HIV infected, and (4) peer navigation support to increase successful health system navigation for HIV-infected MSM and TW in need of ART or HIV engagement in care. METHODS: To assess the effect of HIVST, we will implement a randomized trial in which MSM and TW adults in the greater Yangon metropolitan area who are HIV uninfected will be recruited via RDS (N=366). Participants will complete a baseline socio-behavioral survey and will be randomized to standard, voluntary counseling and testing (VCT) or to HIVST. Biologic specimens will be collected during this baseline visit for confirmatory testing using dried blood spots. Participants will be asked to return to the study office to complete a second study visit in which they will report their HIV test result and answer questions on the acceptability of the assigned testing method. Aim 1 participants with confirmed HIV infection and who are not engaged in care (N=49) will be offered direct enrollment into Aims 2 and 3, which include immediate CD4 POC and the option for peer navigation, respectively. Aims 2 and 3 participants will be prospectively followed for 12 months with data collection including interviewer-administered sociobehavioral survey, CD4 POC, and viral load testing occurring biannually. Participants who accept peer navigation will be compared to those who decline peer navigation. Analyses will estimate the impact of CD4 POC on engagement in care and the impact of peer navigation on ART adherence and viral load. RESULTS: Formative qualitative research was conducted in June and September 2015 and led to further refinement of recruitment methods, HIVST instructions and counseling, and peer navigation methods. Aim 1 recruitment began in November 2015 with subsequent enrollment into Aims 2 and 3 and is currently ongoing. CONCLUSIONS: These innovative interventions may resolve gaps in the HIV care continuum among MSM and TW and future implementation may aid in curbing the HIV epidemic among MSM and TW in Myanmar.

New HIV testing technologies in the context of a concentrated epidemic and evolving HIV prevention: qualitative research on HIV self-testing among men who have sex with men and transgender women in Yangon, Myanmar.

INTRODUCTION: Global effort to increase early diagnosis and engagement in HIV care emphasize the importance of developing novel approaches to reaching those missed by traditional methods. Such needs are particularly great for men who have sex with men (MSM), transgender women (TW), and other populations who face stigma. Myanmar's HIV epidemic is concentrated among key populations and the revised National Strategy aims to reduce late diagnosis and barriers to care to curb HIV incidence among these groups. HIV self-testing (HIVST) may be one method to improve testing and diagnosis among key populations, by placing HIV testing and disclosure within the individual's control. METHODS: Formative, qualitative research including in-depth interviews with adult MSM (N = 12) and TW (N = 13) and focus group discussions with MSM, TW, and community key informants (N = 35) were conducted in June-September 2015 in Yangon, Myanmar. To inform a subsequent HIV care continuum intervention, including HIVST, participants' opinions and perceptions about HIVST were elicited. RESULTS: The confidentiality and privacy of HIVST, particularly as it related to disclosure of HIV status and sexual behaviour, was widely recognized among participants. These major advantages were further supported by the opportunity to avoid stigma, convenience of self-testing (reduced need for transportation and time to go to clinics), and the availability of a pain-free testing option. Participants weighed these benefits against perceived disadvantages of HIVST, the majority of which centred on the perception that HIVST does not include counselling. Participants were concerned that potential lack of counselling would result in poor mental health outcomes, inadequate linkage to HIV care and surveillance, and reductions in disclosure of HIV status. Participants did not view these disadvantages as an impediment, but provided suggestions for future implementation of HIVST in Myanmar. CONCLUSION: MSM and TW are optimistic about the confidentiality and privacy afforded by HIVST but wanted HIV counselling and linkage to appropriate services. The domestic reprioritization of HIV and opening of the country to international support has substantially increased the availability of HIV treatment and provides new opportunities, like HIVST, to potentially improve the HIV response for key populations who are at risk for HIV acquisition.

Measurement of attacks and interferences with health care in conflict: validation of an incident reporting tool for attacks on and interferences with health care in eastern Burma.

BACKGROUND: Attacks on health care in armed conflict and other civil disturbances, including those on health workers, health facilities, patients and health transports, represent a critical yet often overlooked violation of human rights and international humanitarian law. Reporting has been limited yet local health workers working on the frontline in conflict are often the victims of chronic abuse and interferences with their care-giving. This paper reports on the validation and revision of an instrument designed to capture incidents via a qualitative and quantitative evaluation method. METHODS: Based on previous research and interviews with experts, investigators developed a 33-question instrument to report on attacks on healthcare. These items would provide information about who, what, where, when, and the impact of each incident of attack on or interference with health. The questions are grouped into 4 domains: health facilities, health workers, patients, and health transports. 38 health workers who work in eastern Burma participated in detailed discussion groups in August 2013 to review the face and content validity of the instrument and then tested the instrument based on two simulated scenarios. Completed forms were graded to test the inter-rater reliability of the instrument. RESULTS: Face and content validity were confirmed with participants expressing that the instrument would assist in better reporting of attacks on health in the setting of eastern Burma where they work. Participants were able to give an accurate account of relevant incidents (86% and 82% on Scenarios 1 and 2 respectively). Item-by-item review of the instrument revealed that greater than 95% of participants completed the correct sections. Errors primarily occurred in quantifying the impact of the incident on patient care. Revisions to the translated instrument based on the results consisted primarily of design improvements and simplification of some numerical fields. CONCLUSION: This instrument was validated for use in eastern Burma and could be used as a model for reporting violence towards health care in other conflict settings.

Examining correlates of methamphetamine and other drug use in pregnant American Indian adolescents.

American Indian and Alaska Native (AI/AN) adolescents have high rates of pregnancy, as well as alcohol, marijuana, cocaine, and, increasingly, methamphetamine (meth) use. The progression of adolescent drug use to meth use could have devastating impacts on AI communities, particularly when youth are simultaneously at risk for teen childbearing. In order to inform future prevention efforts, this study explores correlates of meth use in a sample of pregnant AI teens, with a focus on sociodemographic, familial, and cultural factors and use of other drugs.

Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill.

The learning of new skills is characterized by an initial phase of rapid improvement in performance and a phase of more gradual improvements as skills are automatized and performance asymptotes. Using in vivo striatal recordings, we observed region-specific changes in neural activity during the different phases of skill learning, with the associative or dorsomedial striatum being preferentially engaged early in training and the sensorimotor or dorsolateral striatum being engaged later in training. Ex vivo recordings from medium spiny striatal neurons in brain slices of trained mice revealed that the changes observed in vivo corresponded to regional- and training-specific changes in excitatory synaptic transmission in the striatum. Furthermore, the potentiation of glutamatergic transmission observed in dorsolateral striatum after extensive training was preferentially expressed in striatopallidal neurons, rather than striatonigral neurons. These findings demonstrate that region- and pathway-specific plasticity sculpts the circuits involved in the performance of the skill as it becomes automatized.

Endocannabinoid signaling is critical for habit formation.

Extended training can induce a shift in behavioral control from goal-directed actions, which are governed by action-outcome contingencies and sensitive to changes in the expected value of the outcome, to habits which are less dependent on action-outcome relations and insensitive to changes in outcome value. Previous studies in rats have shown that interval schedules of reinforcement favor habit formation while ratio schedules favor goal-directed behavior. However, the molecular mechanisms underlying habit formation are not well understood. Endocannabinoids, which can function as retrograde messengers acting through presynaptic CB1 receptors, are highly expressed in the dorsolateral striatum, a key region involved in habit formation. Using a reversible devaluation paradigm, we confirmed that in mice random interval schedules also favor habit formation compared with random ratio schedules. We also found that training with interval schedules resulted in a preference for exploration of a novel lever, whereas training with ratio schedules resulted in less generalization and more exploitation of the reinforced lever. Furthermore, mice carrying either a heterozygous or a homozygous null mutation of the cannabinoid receptor type I (CB1) showed reduced habit formation and enhanced exploitation. The impaired habit formation in CB1 mutant mice cannot be attributed to chronic developmental or behavioral abnormalities because pharmacological blockade of CB1 receptors specifically during training also impairs habit formation. Taken together our data suggest that endocannabinoid signaling is critical for habit formation.