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BackgroundTechnology-based computational strategies that leverage social network site (SNS) data to detect substance use are promising screening tools but rely on the presence of sufficient data to detect risk if it is present. A better understanding of the association between substance use and SNS participation may inform the utility of these technology-based screening tools. ObjectiveThis paper aims to examine associations between substance use and Instagram posts and to test whether such associations differ as a function of age, gender, and race/ethnicity. MethodsParticipants with an Instagram account were recruited primarily via Clickworker (N=3117). With participant permission and Instagram’s approval, participants’ Instagram photo posts were downloaded with an application program interface. Participants’ past-year substance use was measured with an adapted version of the National Institute on Drug Abuse Quick Screen. At-risk drinking was defined as at least one past-year instance having “had more than a few alcoholic drinks a day,” drug use was defined as any use of nonprescription drugs, and prescription drug use was defined as any nonmedical use of prescription medications. We used logistic regression to examine the associations between substance use and any Instagram posts and negative binomial regression to examine the associations between substance use and number of Instagram posts. We examined whether age (18-25, 26-38, 39+ years), gender, and race/ethnicity moderated associations in both logistic and negative binomial models. All differences noted were significant at the .05 level. ResultsCompared with no at-risk drinking, any at-risk drinking was associated with both a higher likelihood of any Instagram posts and a higher number of posts, except among Hispanic/Latino individuals, in whom at-risk drinking was associated with a similar number of posts. Compared with no drug use, any drug use was associated with a higher likelihood of any posts but was associated with a similar number of posts. Compared with no prescription drug use, any prescription drug use was associated with a similar likelihood of any posts and was associated with a lower number of posts only among those aged 39 years and older. Of note, main effects showed that being female compared with being male and being Hispanic/Latino compared with being White were significantly associated with both a greater likelihood of any posts and a greater number of posts. ConclusionsResearchers developing computational substance use risk detection models using Instagram or other SNS data may wish to consider our findings showing that at-risk drinking and drug use were positively associated with Instagram participation, while prescription drug use was negatively associated with Instagram participation for middle- and older-aged adults. As more is learned about SNS behaviors among those who use substances, researchers may be better positioned to successfully design and interpret innovative risk detection approaches.