Effects of regular cannabis and nicotine use on acute stress responses: chronic nicotine, but not cannabis use, is associated with blunted adrenocortical and cardiovascular responses to stress

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 group. After attending a medical screening session, participants completed a laboratory stress session during which they completed measures of subjective states, cardiovascular responses, and salivary cortisol during baseline (rest) and after exposure to acute stress challenges. Results: Nicotine use, but not cannabis use, was associated with blunted cortisol and cardiovascular responses to stress across both men and women. Men exhibited larger cortisol responses to stress than women. Co-users had significantly larger stress-related increases in cannabis craving than cannabis-only users. Cannabis users reported smaller increases in anxiety during stress than cannabis non/light-users, and both male nicotine-only users and male cannabis-only users experienced significantly smaller increases in stress than their non/light-user control counterparts. Conclusions: This study replicates and extends earlier research on the impacts of sex and nicotine use on stress responses, and it provides novel findings suggesting that when co-used with nicotine, cannabis use may not confer additional alterations to physiological nor subjective responses to stress. Co-use, however, was associated with enhanced stress-related craving for cannabis.