One in five young men report being a gang member in the townships of Cape Town and over half of all young men report committing at least one violent act. These findings are not surprising in these post-apartheid neighborhoods characterized by widespread poverty and limited educational and employment opportunities. Young men who report being involved in a gang are more than twice as likely to report ever being arrested. These findings extend previous research on the widespread culture of violence in the townships by examining the association between reports of different types of violence and being arrested in different neighborhoods. Further, SA young men who report being stressed are more likely to have a history of arrests. Prisoners and arrestees in SA, as with many other countries, experience higher rates of neuropsychiatric disorders than the general population. A large-scale longitudinal analysis in the United States reports that individuals with severe mental illness are only more violent if they also experience substance abuse. Mental health symptoms are rarely studied among men,drying cannabis especially in LMIC, and need more investigation. Although rates of food insecurity and unemployment are high in this study, young men living in communities with more formal housing and in-home water sources are more likely to report ever being arrested compared to those in less advantaged communities. Two of the 18 communities with the highest rates of arrests are located in a relatively new township.

Prior to any migrants arriving, the government provided paved roads, access to electricity, housing, and in-home water sources. Because this township has the most immigrants, residents are likely to have fewer ties to the community. Although households may have more infrastructure, the lack of long-standing family ties, along with the difficulty in obtaining employment, may contribute to a high risk of arrests. Research in rural areas of the United States suggests that communities characterized by high ethnic heterogeneity and less local engagement among juveniles are consistently linked to higher rates of arrests. Although all of the young men in this study are Black-African, many migrate from the Eastern Cape in SA, limiting their bonds to the township communities. These findings support the extension of the social disorganization theory to the township neighborhoods if SA. Housing and access to municipal services are disproportionally distributed across three police precincts in Khayelitsha and one police precinct in Mfuleni. For instance, the precinct in Lingelethu West PP includes a much higher proportion of formal housing , compared to those in Khayelitsha and Harare. In contrast, the precinct in Khayelitsha includes 56% informal settlements, compared to 46% in Harare and 25% in Lingelethu West. As certain police precincts include more informal settlements, service delivery and policing become a challenge due to the lack of infrastructure. For the present study, the precincts in Harare covers three of our neighborhoods, of which two are informal settlements. Informal settlements often do not have formal roads and corresponding municipal-issued physical addresses. This may account for the surprisingly higher number of arrests in formal areas in the current study. That is, policing, and subsequent arrests, may be more challenging in informal neighborhoods due to the lack of infrastructure and the police’s ability to detect and detain the accused.

The examination of risk associated with being arrested must consider clusters of individual and community-level factors that can interact to propagate violence, substance use, and potential criminal behavior. This approach helps inform community interventions to create new pathways for young men. There is some evidence that engaging people in community interventions can be an effective way to address public health problems, such as unwanted pregnancy, substance abuse, violence, and delinquency. However, it is notoriously difficult to engage young men in these types of interventions. As recently mentioned by Brooks , “human behavior happens in contagious, networked ways”. Community-level interventions are needed for community-level challenges in South Africa to combat substance use and gang activity. These findings support the need for pathways out of risk that engage young men in prosocial ways and support their access to education. As a first test of this idea, we examined the effects of a well-characterized FAAH inhibitor, the compound URB597, in two established mouse models of ASD: BTBR mice, an inbred strain discovered through the Mouse Phenotype Project, which shows pronounced deficits in social approach, reciprocal social interactions, and juvenile play, and fmr1 / mutant mice—a model of Fragile X Syndrome, the most common monogenetic cause of ASD, which features persistent social deficits.We show that FAAH inhibition substantially improves social behavior in BTBR and fmr1 / mice and that this effect is independent of anxiety modulation.Previously established methods were followed.Test mice were habituated to an empty three-chambered acrylic box . Habituation included a 10-min session in the center chamber with doors closed and then a 10-min session in all chambers with doors open.

Test mice were then tested in a 10-min session. Subjects were offered a choice between a novel object and a novel mouse in opposing side chambers. The novel object was an empty inverted pencil cup and the novel social stimulus mouse was a sex, age, and weight-matched 129/SvImJ mouse. These mice were selected because they are relatively inert, and they were trained to prevent abnormal behaviors, such as biting the cup. Weighted cups were placed on top of the pencil cups to prevent climbing. Low lighting was used—all chambers were measured to be 5 lux before testing. The apparatus was thoroughly cleaned with SCOE 10X odor eliminator between trials to preclude olfactory confounders. Object/mouse side placement was counterbalanced between trials. Chamber time scoring was automated using image analysis in ImageJ. Sniffing time was scored by trained assistants who were unaware of treatment conditions. Excluded were subjects with outlying inactivity.The procedure was based on previously published methods.The maze was made of black Plexiglas and consisted of two open arms and closed arms . The arms extended from a center square . The maze was mounted on a Plexiglas base and raised 39 cm above the ground. Lighting consisted of two 40W incandescent bulbs, each hanging at a height of 1 m above the open arms of the test apparatus. The floor of the apparatus was cleaned with a SCOE 10X odor eliminator between trials. The animals were placed in the center square and allowed to freely explore for 5 min. The amount of time spent in each arm and the number of entries into each arm were quantified by EthoVision 3.1 video tracking system .We used the CB1-receptor inverse agonist, AM251, or the FAAH inhibitor, URB597,to probe the role of anandamide in social behavior of young adult mice. Social activity was evaluated in the widely used social approach test.The mice were placed in a dimly lit three-chambered apparatus and given a choice between a novel inert mouse restrained by an inverted pencil cup in one chamber or a novel object in the opposite chamber.We first evaluated maximally effective doses of AM251 29 or URB597 25 in socially normal C57Bl6J mice and found that neither drug altered the two outcome measures of the test,greenhouse benches namely the time spent in the social chamber and the time spent sniffing the target mouse . In contrast to C57Bl6J mice, BTBR mice show no social preference in the test .However, administration of URB597 significantly increased the time BTBR mice spent in the social chamber and sniffing, to levels that were comparable to those displayed by control, socially normal C57Bl6J mice . The effect of FAAH inhibition on social approach depended on CB1 receptors and, thus, presumably on anandamide accumulation, because it was prevented by concomitant administration of AM251.

The results on time spent in the social chamber are summarized as an index . Using an enzymatic activity assay and LC/MS, we confirmed that URB597 inhibited FAAH and substantially increased the levels of anandamide in the fore brain of BTBR mice , without affecting levels of the other endocannabinoid 2-arachidonoylsn-glycerol . Together, the results suggest that elevated anandamide activity at CB1 receptors corrects social approach behavior in BTBR mice, whereas it does not alter social approach in control C57Bl6J mice.Interpretation of data obtained with BTBR mice is limited by the possibly polygenetic contributions to the phenotype of this inbred strain. Therefore, we asked whether the prosocial effect of anandamide istranslatable to a monogenetic model of ASD-related social impairment. Fmr1 / mutant mice bred on an FVB/NJ background have been reported to exhibit a deficit in social approach.In our hands, however, this deficit was not statistically significant . Nevertheless, we found that acute administration of URB597 , which did not alter the time spent in the social chamber or sniffing in wild type fmr1+/ + mice , increased the time spent by fmr1 / mice in the social chamber and the time spent sniffing to levels to those displayed by control mice . These results suggest that the prosocial action of increased anandamide activity is generalizable across at least two distinct models of ASD-related social impairment, without affecting socially normal animals. We did not test fmr / mice in the elevated plus maze test because these mice display an innate preference for the open arms of the elevated plus maze,which might confound data interpretation.For better or worse, desperate parents are treating their autistic children with various forms of marijuana. Successes have been reported in high-profile anecdotes publicized by social media. This societal experiment highlights the lack of scientific knowledge regarding the therapeutic utility and safety of cannabinoid agents in ASDs. The present study provides an initial test of the idea that enhancing anandamide-mediated endocannabinoid signaling might help to alleviate social impairment in ASD. We show that inhibition of the anandamide-deactivating enzyme FAAH corrects social impairment in two distinct ASD-related models—BTBR and fmr1 / mice. We confirm that FAAH inhibition is an appropriate strategy to elevate levels of anandamide, and thus, anandamide signaling, in BTBR mice. Furthermore, we show that the prosocial action of FAAH inhibition is independent of reducing anxiety in BTBR mice. Together, the results put forth FAAH as a novel therapeutic target for ASD-related social impairment.

Separate lines of previous research suggest the general notion that abnormal endocannabinoid signaling might contribute to ASD. First, endocannabinoids play important roles in neurodevelopment, which is also affected by exogenous cannabinoids.Second, ASD-related alterations in synaptic signaling have been linked to the endocannabinoid system. For example, mutations in neuroligins, a family of ASD-linked synaptic adhesion proteins, impair tonic endocannabinoid signaling.In a related example, we found that deletion of FMRP, the mRNA-trafficking protein missing in Fragile X Syndrome, impairs the formation of a key signaling complex that links metabotropic glutamate receptor-5 and the 2-AG-synthesizing enzyme diacylglycerol lipase-a .Third, ASD-related insults disturb resting endocannabinoid levels or endocannabinoid system components. For instance, we found that chronic isolation increases 2-AG in the prefrontal cortex, without affecting anandamide, and increases both 2-AG and anandamide in the piriform cortex.Furthermore, developmental treatment with valproic acid reduces cerebellar mRNA levels of DGL-a and reduces hippocampal mRNA levels of the 2-AG-hydrolyzing enzyme monoacylglycerol lipase.Importantly, however, these lines of research have not addressed whether deficient endocannabinoid signaling contributes to the core component of ASD—social impairment. A limited literature has hinted at this possibility indirectly by suggesting a role for endocannabinoid signaling in normal social behaviors. Genetic removal of CB1 receptors alters social interactions in mice in a context dependent manner,which may be related to social anxiety and/or cognition.CB1 agonists impair social play in rats.In contrast, genetic removal of FAAH in mice increases social interactions,and FAAH inhibition promotes social play in rats.Thus, the bidirectional modulation of social behavior likely depends on the dose and the identity of the affected circuits. We recently identified a signaling mechanism in male mice by which oxytocin drives anandamide-mediated endocannabinoid signaling to control social reward.In addition, human studies have found that marijuana may enhance sociability and a polymorphism in the CB1 cannabinoid receptor gene modulates social gaze.Given that endocannabinoid signaling has been linked to ASD and might play a role in normal social behavior, we focused the present investigation on the possible role of endocannabinoid signaling in the social impairment component of ASD.