Editorial: Cannabis use and neurocognitive functioning in adolescents

Decades of research suggest that cannabis use during protracted brain maturation has adverse impacts on brain structure, brain function, and neurocognition among adolescents (1)(2)(3)(4). Despite declining use of cannabis among adolescents (5)(6)(7), understanding the effects of cannabis use on adolescent neurodevelopment remains a public health priority, as globally, cannabis remains the most commonly used illicit substance (8). The rise in cannabis potency (9), the greater availability of cannabis products and routes of administration (10,11), and related negative health outcomes (12) necessitates a more thorough understanding of how current cannabis use may be associated with neurocognitive functions among adolescents. This Research Topic includes nine manuscripts describing the effects of cannabis use on adolescent and young adult neurocognition, including learning and memory, executive functioning, and emotion regulation, the role of abstinence on these functions, and how individual differences (e.g, sex, HIV status, other substance co-use, endocannabinoid levels) moderate the observed associations.examined the role of positively valenced facial stimuli on emotion regulation in a Go/No-Go inhibitory control task among adolescents and young adults who had been abstinent from cannabis use for at least two weeks. One of several findings suggested that youth with a previous history of cannabis use exhibited hypoactivation in frontal regions during positive NoGo stimuli, supporting previous findings of altered inhibitory control brain response among individuals with cannabis use (13). Given the cross-sectional findings, future longitudinal studies are needed to determine whether these neural markers represent a risk factor for cannabis use or were a maintained consequence of cannabis use despite a period of abstinence. Further, it is important for studies of emotion regulation to investigate specific emotion regulation domains, rather than global emotion regulation, as a systematic review by Fleury et al. identified that impulse control, goal-directed behavior, and nonacceptance of emotions may be the most prevalent difficulties among youth with cannabis use.One way to understand how a change in cannabis use could affect neurocognitive functioning is seen in the study by Schuster et al. who used contingency management to conduct a randomized clinical trial of four weeks of cannabis abstinence among adolescents to determine if recovery of neurocognitive functions was possible. Four weeks of abstinence was associated with improved inhibitory control on the Stop Signal Task (SST), as indicated by significantly faster reaction time on the SST for individuals who maintained cannabis abstinence relative to adolescents who continued their typical cannabis use. Thus, finding that executive functioning is a domain that may benefit from abstinence may provide critical information for designing intervention studies among adolescents with cannabis use. The significance of this is also evident in the study by Kenyon et al. who identified that cognitive factors that may be related to atypical executive functioning, such as lower resistance to peer influence (14), are strongly associated with greater hazardous cannabis use over a period of 12 months.In addition to investigating task-based functional magnetic resonance imaging and behavior on neurocognitive tasks, it is necessary to determine if abstinence from cannabis use among adolescents may be associated with alterations in network characteristics observed at rest, as previous studies suggest atypical resting state connectivity among youth with cannabis use (15,16). While Baacke et al. did not find any differences overall in network topology between adolescents with cannabis abstinence relative to controls, they did find that sex was an important moderator of network metrics, particularly for males with greater past year cannabis use and earlier age of cannabis use initiation. Given the small sample size of this study, larger samples will be needed to gain a better understanding of network architecture as it relates to cannabis abstinence. Extending this work, several studies in this Research Topic highlight the importance of individual differences and mechanistic pathways underlying cannabis-related neurocognitive outcomes. For example, Nichols et al. demonstrated that heavier cannabis use was associated with poorer performance across multiple cognitive domains in young adults, although patterns among individuals with HIV suggested that mild-to-moderate cannabis use may differentially relate to cognition. Interestingly, among young adults with HIV, mild-to-moderate cannabis use showed patterns suggestive of potential cognitive benefit, possibly reflecting modulation of chronic neuroinflammatory processes.Further highlighting individual variability, Wallace et al. showed that circulating endocannabinoid levels may moderate cannabis-related memory outcomes, with distinct endocannabinoid profiles (e.g., 2-arachidonoil-glicerol (2-AG) versus Narachidonoylethanolamine (AEA)) linked to differential performance among heavy users. In this study, heavy cannabis use was associated with poorer verbal memory performance. However, higher 2-AG levels appeared to mitigate memory deficits, whereas higher AEA levels were associated with worse performance in heavy users. These findings suggest that individual variability in endogenous cannabinoid signaling may shape cognitive outcomes associated with cannabis use, pointing to potential biomarkers of both vulnerability and resilience.At the neurobiological level, Viera Perez et al. identified a longitudinal pathway in which blunted reward-related striatal activity during a Monetary Incentive Delay task predicted subsequent cannabis and e-cigarette use via increased impulsivity and externalizing behaviors approximately one year later. These findings underscore a developmental mechanism of cannabis-related risk and suggest that interventions targeting reward processing and self-regulation may help mitigate vulnerability during adolescence. Finally, Paige et al. used a double-blind cannabis administration paradigm to demonstrate that the acute effects of tetrahydrocannabinol on neurocognitive processes are heterogeneous and influenced by individual differences in cannabis use history and subjective cannabis response. Acute cognitive disruption was more pronounced among individuals with less cannabis use history and those reporting stronger subjective drug effects, consistent with tolerancerelated mechanisms.To date, the current literature on cannabis use and neurocognition among youth has been limited by the predominance of cross-sectional designs, modest sample sizes, variability of cannabis use operationalization, common co-use of cannabis with alcohol and/or nicotine, and limited information on the characteristics of cannabis consumption (e.g., quantity consumed or potency of tetrahydrocannabinol) (17,18). Thus, continued research is needed to advance our understanding of cannabis exposure on neurocognitive functions among adolescents and young adults. Together, this collection of articles underscores that cannabis-related neurocognitive outcomes are not uniform during adolescent development, but rather shaped by biological context, cannabis use characteristics, the social environment, and developmental variability, highlighting the need for more mechanistic and personalized approaches in treatment development research. Importantly, these findings also emphasize the need for continued longitudinal research to better characterize developmental trajectories and disentangle risk factors from consequences of cannabis use over time.