Statement of the problem: Little is known about synthetic cannabinoids (SC) use among adolescents and young adults admitted to residential substance use treatment programs. The purpose of this study is to explore the extent of SC use in this population, identify characteristics of those at greatest risk to use, and examine psychiatric comorbidities, as well as associated risk behavior unique to SC users that may complicate treatment and recovery. Methods: This is a case-control study using retrospective chart review of patients, ages 12-25. SC users (n = 227) were compared to a random sample of nonusers (n = 202). Relationships between SC use (lifetime, recency, and amount of use) and characteristics, psychiatric indicators, and risk behaviors were examined using chi-square comparisons and logistic regression models. Results: Nearly one-third (32.5%) of the youth entering treatment had lifetime SC use. SC use was more common among males (OR=1.64, CI=1.02, 2.63, p=0.04), Whites (OR=1.94, CI =1.18, 3.20, p=0.009), and LGBT identifying youth (OR=2.19, 95%, CI =1.06, 4.52, p=0.04); while it was less common among those preferring opioids (OR=0.49, CI=0.30, 0.80, p=0.004). Persistent use was more common than experimental use in youth with legal involvement (OR=2.17, CI=1.12, 4.27, p=0.02) and having two or more choice drugs (OR=2.80, CI=1.45, 5.42, p=0.002). Youth who reported lifetime SC use had over three times the odds of having a diagnosis of psychotic disorder (OR=3.38, CI=1.89, 9.61, p=0.02). Amount of use and recency of use was not significantly associated with psychotic disorders. Lifetime SC users were more likely to be prescribed an antipsychotic medication (OR=1.89, 95%, CI=1.18, 3.05, p=0.01). Lifetime hallucinogen use was a behavior associated with lifetime SC use (OR=1.68, 95%, CI=1.08, 2.62, p=0.03). Conclusions: SC use was fairly common among these patients. Recognizing personal characteristics and risk behaviors that are associated with SC use may help health care providers to recognize users and those at risk of using; however, it is important to screen all patients. Prevention strategies for youth are needed, especially for those with legal involvement and who identify as LGBT. Psychiatric morbidity such as psychosis is associated with SC, which may complicate treatment.