Sex Differences in Neuropsychological Functioning are Domain-Specific in Adolescent and Young Adult Regular Cannabis Users.

George Savulich,Barbara J. Sahakian,Erin Lamberth,Maya Hareli,Randi M. Schuster,Natali Rychik,A. Eden Evins

doi:10.1017/s1355617720001435

Abstract

Adolescence into young adulthood represents a sensitive period in which brain development significantly diverges by sex. Regular cannabis use by young people is associated with neuropsychological vulnerabilities, but the potential impact of sex on these relationships is unclear. In a cross-sectional study, we examined sex differences in multi-domain neuropsychological functioning using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and tested whether sex moderated the relationship between cognitive performance and age of initiation, frequency of cannabis use, amount of cannabis use, and withdrawal symptoms in at least weekly adolescent and young adult cannabis users (n = 171; aged 13-25 years; 46.2% female). Male cannabis users had poorer visual recognition memory and female cannabis users showed worse attention and executive functions, with medium to large effect sizes. These sex effects persisted, when controlling for age, IQ, amount of alcohol and nicotine use, mood and anxiety symptoms, emotional stability and impulsive behavior. Earlier age of initiated use and more use were associated with worse attentional functions in females, but not males. More use was more strongly associated with worse episodic memory in males than in females. More use was associated with poorer learning in males only. Domain-specific patterns of neuropsychological performance were found by sex, such that males showed poorer visual memory and females showed worse performance on measures of attention (sustained visual, multitasking) and executive functioning (spatial planning/working memory subdomains). Larger studies including healthy controls are needed to determine if the observed sex differences are more exaggerated relative to non-users.

Highlights

Cannabis is one of the most widely used substances in the world, and is one of the most commonly used substances among adolescents and young adults in high-income countries (Hall & Degenhardt, 2009)
As findings from adult studies are unlikely to generalize to younger populations, our study evaluated sex differences in neuropsychological functioning in a large, generalizable sample of adolescent and young adult regular cannabis users
Our study showed that sex differences in neuropsychological functioning are domain-specific, which may reflect sex-related disruptions in frontal-limbic circuitry that emerge prior to or as a result of regular, early-onset cannabis use

Summary

Introduction

Cannabis is one of the most widely used substances in the world, and is one of the most commonly used substances among adolescents and young adults in high-income countries (Hall & Degenhardt, 2009). In the United States, 12.5% of adolescents aged 12 to years and 34.8% of young adults aged to 25 years used cannabis in the past year (Substance Abuse and Mental Health Services Administration, 2019), with around 5% of high school students reporting daily use (Johnston et al, 2020). The continued legalization and commercialization of cannabis for medicinal In female users aged 16 to 18 years, larger volume of the prefrontal cortex (PFC) has been reported to have an association with poorer executive functioning (Medina et al, 2009)

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