AbstractAimsTo estimate the effect of recreational legalization on cannabis use frequency and sources of variance across legal environments.DesignLongitudinal discordant twin and gene–environment interaction models in twins recruited from birth records and assessed prospectively.SettingThe United States, including states with different recreational cannabis policies before and after 2014, when recreational cannabis was first legalized.ParticipantsTwo longitudinal, prospectively assessed samples of American twins aged 24–47 (n = 1425 in legal states, n = 1996 in illegal states), including 111 monozygotic pairs discordant for residence.MeasurementsCurrent cannabis use frequency (measured continuously and ordinally) was the primary outcome, and the predictor was recreational status of cannabis (legal/illegal) in the participant’s state of residence at the time of assessment. Covariates include age, sex and cannabis use frequency prior to 2014.FindingsAccounting for pre‐2014 use, residents of legal states used cannabis more frequently than residents of illegal states (b = 0.21, P = 8.08 × 10⁻⁵). Comparing 111 pairs of monozygotic twins discordant for residence confirmed the effect (b = 0.18, P = 0.014). There was inconclusive evidence for genetic influences on cannabis use frequency that were specific to the legal environment [χ² = 2.9 × 10⁻⁹, degrees of freedom (d.f.) = 1, P > 0.999]. Existing genetic influences were moderated by the legal environment, as the genetic correlation between marijuana use before and after legalization was lower in states that legalized (r_genetic = 0.24) compared with states that did not (r_genetic = 0.78, P_difference = 0.016).ConclusionsIn the United States, there appears to be a ~ 20% average increase in cannabis use frequency attributable to recreational legalization, consistent across increasingly rigorous designs. In addition, the heritability of cannabis use frequency appears to be moderated by legalization.