IntroductionFlavourants and humectants in waterpipe tobacco (WT) increase product appeal. Removal of these constituents, however, is associated with increased intensity of WT puffing, likely due to reduced nicotine delivery efficiency. To clarify the potential public health outcomes of restrictions on flavourants or humectants in WT, we evaluated the effects of these constituents on puffing behaviours, biomarkers of exposure and subjective effects among adults with high versus low WT dependence.MethodsN=39 high dependence and N=49 low dependence WT smokers (Lebanese Waterpipe Dependence Scale scores>10 = high dependence) completed four smoking sessions in a cross-over experiment. Conditions were preferred flavour with humectant (+F+H), preferred flavour without humectant (+F-H), unflavoured with humectant (−F+H) and unflavoured without humectant (−F−H). Measures of puff topography, plasma nicotine and expired carbon monoxide (eCO) boost, and subjective effects were assessed.ResultsLevel of WT dependence modified the effect of WT condition on average flow rate, average puff volume and eCO boost. Although, overall, participants puffed the +F+H WT least intensely and −F−H WT most intensely, this association was strongest among WT smokers with high dependence. Participants preferred smoking the +F+H WT and achieved the largest plasma nicotine boost in that condition.DiscussionFindings underscore the complexity of setting product standards related to flavourants and humectants in WT. Future research evaluating whether WT smokers with high dependence would quit or reduce their WT smoking in response to removal of flavourants or humectants from WT is necessary to appreciate the full public health effects of such policies.