Please use this link to access this publication. Abstract Rationale Cannabis is one of the most prevalent substances used by tobacco smokers and, in light of the growing list of states and territories legalizing cannabis, it is expected that co-use of cannabis and nicotine will escalate significantly and will lead to continuing challenges with tobacco use. Objectives This study was conducted to examine the interactive effects of chronic cannabis and nicotine use on adrenocortical, cardiovascular, and psychological responses to stress and to explore sex differences in these effects. Methods Participants (N = 231) included cannabis-only users, nicotine-only users, co-users of both substances, and a non/light-user comparison...