A few questions still remain, such as whether heavy substance use during adolescence causes cognitive impairments and changes in neurodevelopment, if and when are critical periods of heightened vulnerability to such effects, and if observed abnormalities remit with reduced use. We have the capability to design studies in which we restrict or control for nicotine and most other drug use, but few adolescent drug users do not also use alcohol. It is also important to understand if results generalize to youth with psychiatric problems, other substance use histories, and low socioeconomic status, and to further explore implications for changes in brain activation for learning and behavioral control, along with mood and psychiatric illness. Harder parametric tasks that include conditions on which behavior does differ between groups would help us better understand the cognitive domains we have observed differences on. Lastly, we need to better understand the biochemical changes that may mediate macrostructural, microstructural, and functional neuronal changes in response to substance use, such as cannabinoid receptor activity changes. Multimodal approaches to neuroimaging may help us disentangle such questions (e.g., PET, spectroscopy).
