Cannabis Use in Adolescence: Vulnerability to Cognitive and Psychological Effects

Abstract

Worldwide, cannabis is more widely used than all other classes of illicit drugs combined (1). Despite the perception of cannabis as a low-risk drug, the proportion of treatment admissions for cannabis, relative to other drugs, is high. In addition, it is the most frequently used illicit drug among adolescents. Compared with a few decades ago, cannabis strains are increasingly potent, while at the same time, adolescents view it as being less harmful than they used to (1). The high frequency of cannabis use seen in adolescents is important, as there is emerging evidence that the adolescent brain may be uniquely vulnerable to its effects. Adolescent cannabis use may have particularly long-term impacts on neural structure, neural function, cognition, and behavior. There are several reasons why the unique neurodevelopmental processes occurring during adolescence might impart a special vulnerability. Across the lifetime, in the prefrontal cortex there are changes in the density of cannabinoid CB1 receptors, the type of cannabinoid receptors agonized by D-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis. There are also changes in the distribution of CB1 receptors among cortical layers (2). Interestingly, regions known to continue maturing during adolescence and that have been associated with both higher-level cognition and psychopathology, such as the hippocampus, amygdala, and dorsolateral prefrontal cortex, have high densities of CB1 receptors. Exposure to THC may disrupt the typical patterns of prefrontal cortex maturation, and in particular the normal dendritic pruning process that occurs in adolescence. Consistent with these findings, cannabis use in adolescence has been associated with structural alterations in the prefrontal cortex. Therefore, it is critical to understand not only the acute impact of cannabis exposure on the adolescent brain but also the impact that cannabis use may have on the neurodevelopmental trajectory and on functional outcomes during this important period (3). Several aspects of higher-level cognition, including executive function, are known to continue to mature across adolescence and even into early adulthood. Behaviorally, preclinical rodent data indicate that adolescent cannabis exposure may have a significant impact on cognition that may be more severe than the impact from adult usage (4). Likewise, human data indicate that initiation of use during adolescence is associated with more severe cognitive impairment, as well as functional disruptions during working memory tasks (3). Thus, the article by Ho et al. (5) in the current issue of Biological Psychiatry: Global Open Science, which focuses on cognitive impacts and particularly on executive function changes caused by cannabis use, is of particular importance.