An initial test of biobehavioral mechanisms of sleep health alterations in the context of adolescent cannabis use using objective methods

Cannabis use (CU} is linked to sleep health domains. In adults, chronic CU has impacted sleep architecture by decreasing REM and slow-wave sleep. There is a dearth of knowledge on adolescent CU and sleep in general and from using objective sleep measures specifically, despite the endocannabinoid system playing a role in both regulating sleep and facilitating adolescent brain development. The dopaminergic system, substantially developing during adolescence and vulnerable to disruption by CU, plays a critical role in reward, motivation, and arousal. Dopamine is a wake-promoting neurotransmitter yet is also blunted by chronic CU. How neurobehavioral developmental changes during adolescence associated with sleep impact problematic CU and exacerbation is unknown, curbing prevention and intervention efforts. The research objectives of this proposal are to characterize sleep health processes in adolescent CU using multimodal objective assessments. The central hypothesis is that CU during adolescence is associated with altered neurobiology that influence sleep health processes and cannabis use disorder (CUD} severity. The project will enroll 40 adolescents ages 14-15, half of whom have had at least weekly CU for the past three months, who will undergo at baseline a sleep latency paradigm during fMRI in which they will complete in random order a resting state MRI while awake, and while instructed to try-to-sleep (TIS; 7 min each; within-subject) to characterize resting state network connectivity during ITS. Another scan will obtain an indicator of mesolimbic dopamine neurophysiology. Next, adolescents will start a 5-day assessment with at-home EEG and actigraphy devices. We will assess CU from 3 months pre-baseline through 3-months post-baseline, and CUD symptom severity will be measured at baseline and 3-months. Aim 1 will identify how cannabis teens differ from controls on sleep architecture and actigraphy-measured sleep indices. Aim 2 will test how brain connectivity indices during TTS differ between controls and cannabis teens. Aim 3 will evaluate the link between mesolimbic tissue iron and sleep health indices and describe how these differ for controls vs. cannabis teens. This proposal is significant by addressing sleep health processes influencing the development and worsening of addiction in the context of adolescent CU, and innovative by using objective sleep measures, an experimental sleep paradigm during fMRI, and brain tissue iron measurements as an indicator of dopamine neurophysiology.