The aims of this study were: (a) to estimate time trends in the prevalence of the co-use of cannabis and other cannabis-based products (CBP) with the misuse of tranquilizers, sedatives, and sleeping pills (TSSp) between 2009 and 2015; and (b) to identify the factors associated with the probability of the co-use of CBP with TSSp misuse during this period among Spanish younger adults (15–34 years old). We analyzed data collected from the Spanish National Surveys on Alcohol and Other Drugs (EDADES) in 2009, 2011, 2013, and 2015. CBP co-use with TSSp misuse were the dependent variables. We also analyzed sociodemographic features, self-perceived health status, lifestyle habits, perceived health risk of consumption, and perceived availability of substance using logistic regression models. The prevalence of CBP co-use with TSSp misuse has decreased in Spain. The factors associated with co-use were a lack of education (OR 2.34), alcohol (OR 7.2), tobacco (OR 6.3) and other illicit psychoactive drug (OR 6.5) consumption, perceived non-health risk for the consumption of CBP and TSSp (OR 3.27), and perceived availability of CBP (OR 2.96). Our study identified several factors that appear to affect CBP and TSSp co-use in younger adults, with potential implications for healthcare providers.