The present study found no effect of adolescent cannabinoid exposure in the escalation model, suggesting that adolescent WIN exposure may not facilitate the acquisition, maintenance, or escalation of cocaine use in adulthood. An alternative hypothesis is that the effect of cannabinoid use may not be observed on cocaine intake per se; instead, cannabinoid exposure may produce an increase in the motivation for cocaine, leading to an increase in compulsive cocaine seeking. Indeed, prior exposure to another potential gateway drug, alcohol, was found to have no effect on subsequent cocaine self-administration per se but produced greater motivation and compulsive-like cocaine seeking under a PR schedule of reinforcement. However, we observed no differences between the WIN-exposed and control groups in adulthood when we used a PR schedule of reinforcement to examine whether rats with prior exposure to WIN express alterations of the motivation to self-administer cocaine.One limitation of long-term behavioral studies in adolescent rats, including the present study, is that puberty in rats is relatively short . Compared with adults, rats that are allowed to self-administer cocaine during adolescence have been shown to be more vulnerable to cocaine addiction. Unfortunately, in the model of cannabinoid exposure during adolescence , cocaine self-administration can only be studied starting in late adolescence and continuing into adulthood because rats exit puberty by PND60. Because of this limitation, one possibility is that cannabinoid exposure during adolescence may affect cocaine intake in adolescence. The present results demonstrate that chronic exposure to cannabinoids does not facilitate the acquisition of cocaine self-administration or compulsive-like cocaine intake in adulthood, hydroponic table measured by the escalation of cocaine self-administration and PR responding in a relevant model of cocaine use disorder.
These results suggest that cannabinoid exposure per se is unlikely to be causally responsible for the association between prior cannabis use and future cocaine use in adulthood as purported by the gateway hypothesis. However, we found that cannabinoid exposure produced long-lasting increases in irritability-like behavior, which may indirectly facilitate the emergence of social conflicts and other mental disorders that may contribute to the abuse of drugs other than cocaine. Additionally, the cross-sensitization between WIN and cocaine in adolescence—which was not observed in adulthood—may highlight a short-term increase in the vulnerability to cocaine-induced behaviors. In summary, the present results showed that cannabinoid exposure during adolescence in rats produced cross-sensitization to cocaine in adolescence and a long-lasting increase in irritability-like behavior in adulthood. However, it did not facilitate the acquisition or escalation of cocaine self-administration or compulsive-like responding for cocaine in adulthood.Marijuana is the most widely used controlled substance in the world . In 2016, 192.2 million people used marijuana . Regular marijuana use, particularly initiated in adolescence, is associated with a range of adverse consequences, including poor cognitive and educational outcomes, low self-reported life satisfaction , downward socioeconomic mobility , psychiatric illness , marijuana-involved injury , and substance use disorders . Perceived risk and perceived availability of marijuana have historically been important drivers of adolescent marijuana use, and often targets of interventions to prevent or reduce adolescents’ use . However, these relationships may be changing. Most extant research on the changing associations between adolescent perceived risk, availability, and use of marijuana has been conducted in the United States , where 28 states and the District of Columbia have legalized medical marijuana since 2000, and 10 states and DC have legalized recreational marijuana since 2012 .
In this context, more adolescents now perceive no/low risk of marijuana use, but the prevalence of marijuana use has not increased simultaneously . Research on changes in the individual-level association between no/low perceived risk and use has been mixed. Some have found that the association weakened in recent years , while others have reported that it strengthened or remained stable . Additionally, perceived easy availability of marijuana has largely declined among US adolescents . Evidence suggests that the association between perceived availability and use of marijuana has remained strong and stable over time . Understanding these relationships is particularly important in light of recent liberalization of marijuana access, as perceived risk and availability are two key mechanisms through which legalization could impact use. In this study, we focus on the Southern Cone context for two reasons. First the Southern Cone has recently experienced changes in marijuana regulation, which could impact perceived risk and availability. Second, trends in adolescent marijuana use and perceived availability are different from those in the US, which could suggest distinct relationships between perceived risk and availability and use of marijuana. In 2013, Uruguay enacted a law providing the government full regulation over the large scale production and sale of recreational marijuana. Adults in Uruguay can purchase marijuana at pharmacies, grow marijuana at home, or acquire it through a cannabis club . In Argentina, possession of marijuana for personal use continues to be illegal ; however, a 2009 court judgment marked the beginning of a paradigm shift in the criminalization of marijuana since it raised a contradiction between Law 23,737 and Article 19 of the Constitution, which protects individuals’ freedom from state regulation . In 2017, Argentina approved access to medical marijuana under specific circumstances . In Chile, marijuana is decriminalized, a limited set of cannabis-based pharmaceutical products are available for medical use, and a new bill allowing other sources of access and formulations is under debate .
Since the early 2000’s, past-month adolescent marijuana use has increased in Uruguay , Chile , and Argentina . These trends are distinct from the US where marijuana use has remained stable , and from other South American countries where past-year use is less than 5% . Although perceived risk of marijuana use has decreased in both the Southern Cone and the US, perceived availability has increased in the Southern Cone, but decreased in the US . We know of no study that has assessed the individual-level relationships between adolescent perceived risk, availability, and use of marijuana in the context of the Southern Cone. Such research may inform the priority and scope of context-specific public health interventions to prevent adolescent marijuana use and help identify the drivers of use during these historical shifts. As more regions debate or enact policies to decriminalize or legalize marijuana use, the impetus for cross-country comparisons increases. Individual-level data from adolescents enrolled in secondary education in Uruguay, Chile, and Argentina were obtained from the National Surveys on Drug Use Among Secondary School Students . These cross sectional surveys, carried out every 2–3 years, collect information on substance use and related risk factors. The sampling design and survey instruments are similar to the Monitoring the Future Surveys and were implemented comparably across countries. Surveys were self-report and administered confidentially in students’ classrooms. The sample included 8th, 10th, and 12th graders in schools classified as public, private, and other in mostly urban areas. Net secondary school enrollment was 80–90% in Chile and Argentina over the last decade and increased from 67.6–82.8% from 2007 to 2016 in Uruguay . The sample was selected via clustered, multistage random sampling from areas with 10,000+ and 30,000+ inhabitants in Uruguay and Chile, respectively, greenhouse tables and schools with at least 20 students in the grades under study in Argentina. In Uruguay and Argentina, strata were types of school within urban areas of geographical regions in each country; primary sampling units were schools followed by classrooms. In Chile, strata were school type by grade within mostly urban areas and primary sampling units were classrooms. Individual-level survey weights were used. Recent school cooperation rates ranged from 76–86%. This study was determined not human subjects research by the University of California, Davis Institutional Review Board.Consistent with prior studies from South America and the US, our results indicate that the less risk an individual attributes to marijuana use, the more likely he/she is to use marijuana . However, in the Southern Cone countries, the overall magnitude of this association weakened, although it strengthened again most recently in Argentina. This suggests that risk perceptions became a weaker correlate of adolescent marijuana use over time. There are several implications of these results. First, given the overall increase in the proportion of adolescents who perceive marijuana use to pose no/low risk of harm, marijuana use would have likely increased to a greater degree in the Southern Cone had the risk/use relationship not weakened. Second, factors other than risk perceptions, such as marijuana availability, may have played a greater role in the increase in adolescent marijuana use observed during our study period. This highlights the need to consider changes in multiple individual and environmental determinants of marijuana use. Third, there may be a cross-national weakening of the risk/use relationship. We found this trend in all Southern Cone countries, and some have identified the weakening of this relationship in the US as well . This would suggest that risk perceptions may be, at least in part, shaped by broader societal norms that extend beyond local or national context. Increases in global information sharing via internet use, social media, and international news coverage may contribute to this trend .Consistent with extant research in Europe and the US , we found that adolescents who perceive marijuana to be easily available are more likely to use marijuana. However, the stability of this association varied over time and between countries.
In Chile, the availability/use association weakened, and became increasingly similar to the risk/use association, both in magnitude and trajectory, when risk and availability were modeled together. In contrast, the relationship between availability and use strengthened in Argentina and Uruguay, becoming stronger at times than the relationship between perceived risk and use in both countries. However, because we were not able to model both variables together in Argentina and Uruguay due to finite sample limitations, it is unclear how the associations relate to one another. Variation in the relationship between perceived availability and use of marijuana over time and between countries may be explained by several factors. First, different trends in availability by country may explain differences in the contribution that perceived availability makes to marijuana use. In Chile, perceived availability generally declined from 2001 to the late 2000’s and then increased until 2016, though at lower rates than use. For example, marijuana availability may depend on where individuals buy, grow, or use marijuana, neighborhood police presence and enforcement of laws, or norms about diversion of marijuana to youth . Second, alternative contributing causes of marijuana use may have arisen in Chile to a greater extent than in Uruguay and Argentina, displacing the contribution that perceived availability make to marijuana use. Such factors may include changes in peer or family substance use , changes in the illegal drug market , or social and cultural changes toward marijuana, influenced by strong lobbying for drug policy reform–particularly for cannabis– in a context of massive social movements among students . While examination of such exposures was outside the scope of the current study, future research should examine whether the contribution of perceived availability and risk to marijuana use is moderated by other potential contributing causes in the local environment. In Uruguay, the increase in perceived availability is not surprising, as the 2013 law created a concrete path to marijuana access for adults. Therefore, greater perceived availability in Uruguay likely corresponds to greater actual availability. For example, it is possible that a surplus of self-cultivated marijuana has tipped over into the streets. Second, even though minors cannot buy it, marijuana may seem more accessible because it sold to adults in pharmacies. Third, there may be increased exposure to marijuana use and contact with peers or family members who use marijuana, which could predictably result in a growing sense of availability. Our findings provide several insights about the availability/use association. First, in this region, where marijuana regulation is becoming progressively liberal and where adolescent marijuana use is increasing, perceived availability may be an increasingly important driver of marijuana use trends . Second, given the strengthening of the availability/use relationship in Argentina and Uruguay, and the high prevalence of perceived easy availability in all three countries, public health professionals in the Southern Cone may consider devoting additional resources towards regulating and intervening on the pathways by which adolescents gain access to marijuana. Relatedly, our findings raise questions about how perceptions of availability relate to real access to marijuana, including how adolescents most often obtain marijuana and whether modes of acquisition have changed over time.