<p>Substance regulation in the USA is in a crisis. Here we explore whether seemingly misaligned policies contradict public preferences or reflect biased citizen opinions. Using survey data (<i>N</i> = 5,053), we show that policy outcomes align with public opinion. We further demonstrate that regulatory preferences are driven by status quo bias: support for the legality of legal substances exceeds that for hypothetical drugs with corresponding properties (Δ_{median drug} = 39.33, 95% confidence interval 35.34 to 43.20), while the opposite holds for illegal drugs (Δ_{median drug} = −12.59, 95% confidence interval −15.44 to −9.87). Randomly assigning individuals to information about harm attenuates the status quo bias in the case of legal substances (Δ_{median drug} = −17.70, 95% confidence interval −22.35 to −13.05) but not for illegal ones. We discuss implications for public control over drug policies.</p>