School-based drug prevention programs represent a widely endorsed public health goal, with an important aspect of knowledge-based curricula being education about the physiological effects of drugs. Nicotine is one of the world’s most addictive substances and in this program we have used nicotine-induced mammalian-like behaviors in flatworms called planarians to successfully teach students (4th-12th grade; n = 1,616 students) about the physiological and addictive effects of nicotine. An initial study tested the change in knowledge about addictive substances in 6th-12th grade students after they completed a lab examining the effects of two concentrations of nicotine on the number of stereotypies (C-shaped spasms) planarians demonstrate in a 5-minute period of time. Lab discussion focused on developing and testing hypotheses, measurement reliability, and mechanisms of nicotine action. Surveys given pre- and post-lab experience showed that 6th grade students have significantly lower knowledge about nicotine than 7th-12th grade students (6th grade: 40.65 ± 0.78% correct, 7th-12th grade: 59.29 ± 1.71%, p < 0.001) pre-lab, but that students in all grades showed a significant increase in knowledge post-lab (p < 0.001). In 6th grade the lab was effective in improving knowledge about nicotine in urban, suburban and rural schools, p < 0.001, with students in suburban schools showing significantly greater knowledge both pre-test (urban: 37.62 ± 1.45%; suburban: 48.78 ± 1.62%; rural: 37.33 ± 0.99%; p < 0.001) and post-test (urban:60.60 ± 1.85%; suburban: 67.54 ± 1.82%; urban: 61.66 ± 1.18%; p < 0.001).A second study, modifying the lab so that the time spent observing the planarians is reduced to a 1-minute period, showed that students in both 4th and 5th grades had a significant increase in knowledge about the physiological and addictive effects of nicotine post-lab (p < 0.001).