Background Adolescent cannabis use is associated with adverse later-life effects so identifying factors underlying adolescent use is of substantial general public health importance. the relationship between state MML and adolescent cannabis use. Methods Data came from 1 98 270 U.S. adolescents in 8th 10 and 12th grade in the national Monitoring the Future annual surveys carried out between 1991-2014. The main end result was any cannabis use in the prior 30 days. Using multilevel regression modeling we examined cannabis use in adolescents nested within claims including whether cannabis use was higher overall in claims that ever approved a MML up TSU-68 (SU6668) to 2014 and whether the risk of use changed after state MML were approved. Individual- school- and state-level covariates were controlled. Findings Overall cannabis use was more prevalent in claims that enacted MML up to 2014 than in additional claims (AOR=1.27 95 Pre- and post-MML risk did not differ in the full sample (AOR=0.92 95 A significant connection (p<0.001) indicated differential post-MML risk by grade. In TSU-68 (SU6668) 8th graders post-MML use decreased (AOR=0.73 95 while no significant change occurred in 10th or 12th graders. Results were generally strong across level of sensitivity analyses. Interpretation Earlier evidence and this study display that MML passage does not result in improved adolescent cannabis use. However overall adolescent use is definitely higher in claims that ever enacted MML than in additional states. State-level risk factors other than MML may contribute to both cannabis use and MML warranting investigation. An observed 8th-grade post-MML decrease also merits further study. Funding U.S. National Institute on Drug Abuse Columbia University or college Mailman School of Public Health New York State Psychiatric Institute. In the United States adolescent cannabis use has improved since the mid-2000s1 2 Adolescent use of cannabis particularly regular use is associated with improved probability of deleterious effects including short-term impairments in memory space coordination and judgement and longer-term risk of modified brain development cognitive impairments and habit3 4 TSU-68 (SU6668) Consequently identifying factors underlying TSU-68 (SU6668) adolescent use is of considerable importance. To affect prevalence nationally factors must influence wide segments Cxcr2 of the population. State medical cannabis laws (MML) have been proposed as one such element5-7. Since 1996 23 U.S. claims and the Area of Columbia approved MML and additional states are considering such laws. The specifics of state MML8 differ but they all have a common purpose: to legalize cannabis use for medical purposes. By conveying a message about acceptability or lack of negative health effects passage of state MML could impact youth belief of harms leading TSU-68 (SU6668) to improved prevalence of cannabis use in the years immediately after passage even with delayed implementation or narrow limits on use. Whether MML passage is associated with improved adolescent cannabis use remains unclear. Some suggest that MML have no effect or discourage use9 10 Others suggest that MML increase adolescent cannabis use through various mechanisms5 e.g sending a message that cannabis use is acceptable6 7 In one study 55 of adolescents in pediatric methods in non-MML claims thought MML passage would “help to make it easier for teens to start to smoke cannabis for fun”11. In 2013 18.8% of high school seniors reported they would try cannabis or use it more often if it were legalized12. These findings suggest that MML could increase adolescent cannabis use. Previously we showed that adolescent13 and adult14 cannabis use was more prevalent in claims with MML than in additional states. However limited time periods were examined and the studies did not address whether higher prevalence preceded or adopted MML passage15 16 A comparison of Colorado to non-MML claims suggested that adolescent cannabis use improved post-MML17. Other studies (of four18 and five claims19; seven claims total due to overlap) did not find improved adolescent cannabis use post-MML. However sample sizes claims and years were limited leaving questions about whether the lack of effect might be due to limited statistical power or the particular states studied. Analyzing a greater number of participants years and claims should more definitively set up whether MML.