Cannabis is the most prevalent illicit drug used by adolescents worldwide. Over the past 40 years, changes in cannabis potency through rising concentrations of Δ-9-tetrahydrocannabiol (THC), decreases in cannabidiol, or both, have occurred. Epidemiological and experimental evidence demonstrates that cannabis with high THC concentrations and negligible cannabidiol concentrations is associated with an increased risk of psychotic outcomes, an effect on spatial working memory and prose recall, and increased reports of the severity of cannabis dependence. However, many studies have failed to address cannabis use in adolescence, the peak age at which individuals typically try cannabis and probably the most vulnerable age to experience its harmful effects. In this Review, we highlight the influence that changing cannabis products have on adolescent health and the implications they carry for policy and prevention measures as legal cannabis markets continue to emerge worldwide.