Adolescent Substance Use and the Brain: Behavioral, Cognitive and Neuroimaging Correlates

Abstract

Adolescence is an important ontogenetic period that is characterized by behaviors such as enhanced novelty-seeking, impulsivity, and reward preference, which can give rise to an increased risk for substance use. While substance use rates in adolescence are generally on a decline, the current rates combined with emerging trends, such as increases in e-cigarette use, remain a significant public health concern. In this review, we focus on the neurobiological divergences associated with adolescent substance use, derived from a cross-sectional, retrospective, and longitudinal studies, and highlight how the use of these substances during adolescence may relate to behavioral and neuroimaging-based outcomes. Identifying and understanding the associations between adolescent substance use and changes in cognition, mental health, and future substance use risk may assist our understanding of the consequences of drug exposure during this critical window.

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

“…Cannabis use status was not associated with imaging outcomes in males, but males with higher monthly cannabis use and earlier cannabis use onset had lower cerebellar gray and white matter volume, respectively (Rossetti et al, 2019). Other studies have identified sex differences in neural circuitries underlying SUDs using resting state functional connectivity, and these have been reviewed elsewhere (Hamidullah, Thorpe, Frie, Mccurdy, & Khokhar, 2020;Rakesh, Allen, & Whittle, 2020).…”

Alcohol and Vapourized Nicotine Co-Exposure During Adolescence Contribute Differentially to Sex-Specific Behavioural Effects in Adulthood

“…The adolescent brain undergoes critical neuronal and structural development, making adolescence a period of vulnerability to the effects of drugs 9 , with brain imaging studies suggesting altered brain structure and function in adolescent users compared to non-users 9 . However, the causal consequences of adolescent co-use cannot be systematically examined in humans and thus, animal models are required to explore the cause-effect relationship.…”

Discordant Effects of Cannabinoid 2 Receptor Antagonism/Inverse Agonism During Adolescence on Pavlovian and Instrumental Reward Learning in Adult Male Rats

“…In addition, adolescents are especially vulnerable to drug use. Cannabis is one of the most commonly used drugs among this age group, so understanding the impact of adolescent cannabinoid exposure is of utmost importance (Hamidullah et al, 2020(Hamidullah et al, , 2021. Previous human and animal studies suggest that adolescent exposure to cannabinoids dysregulates ECS activity, which may have long-term behavioral implications that can persist into adulthood (Hamidullah et al, 2020;Thorpe et al, 2020).…”

“…Cannabis is one of the most commonly used drugs among this age group, so understanding the impact of adolescent cannabinoid exposure is of utmost importance ( Hamidullah et al, 2020 , 2021 ). Previous human and animal studies suggest that adolescent exposure to cannabinoids dysregulates ECS activity, which may have long-term behavioral implications that can persist into adulthood ( Hamidullah et al, 2020 ; Thorpe et al, 2020 ). For instance, treatment of adolescent rats with the CB1R/CB2R agonist WIN55,212-2 ( Schoch et al, 2018 ) or the CB1R/CB2R partial agonist and the primary psychoactive constituent of cannabis Δ9-tetrahydrocannabidiol (THC) ( Kruse et al, 2019 ) have been shown to modulate the response to food-predictive cues in adulthood.…”