Commentary: Substance use and the brain: it is not straightforward to differentiate cause from consequence - a...

That substance abuse is associated with differences in brain structure and function, and related neurocognitive impairment is undisputed. Causally informative study designs, such as the prospective, longitudinal study leveraged by Kim-Spoon et al. (2020), as well as twin and family studies, are necessary for answering vexing but critical questions about substance use and the developing brain. Investigations that seek to differentiate cause from consequence and identify the factors that initiate the cycle of addiction have the potential to transform our understanding of the development of substance use and abuse, prompt revisions to current models of addiction, guide the most strategic preventive-intervention efforts, and ultimately improve the lives of millions of affected individuals and their families.