Families with greater cannabis use showed poorer general cognitive ability, yet within families, twins with more use rarely had lower scores; overall, there is little evidence of causal cannabis effect on cognition

Investigating the Causal Effect of Cannabis Use on Cognitive Function with a Quasi-Experimental Co-Twin Design. J. Megan Ross et al. Drug and Alcohol Dependence, November 2 2019, 107712. https://doi.org/10.1016/j.drugalcdep.2019.107712

Highlights
• Cannabis use and cognition showed small but significant phenotypic associations.
• Families with greater cannabis use showed poorer general cognitive ability.
• Yet within families, twins with higher use rarely had lower cognitive scores.
• Overall, there was little evidence for causal effect of cannabis on cognition.

Abstract
Background It is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect. Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study.

Methods We first examined the phenotypic associations between cannabis initiation, frequency, and use disorder with cognitive abilities, while also controlling for pre-use general cognitive ability and other substance involvement. We tested the concurrent association between the cannabis use variables and cognitive abilities in late adolescence and young adulthood and the longitudinal association between cannabis use variables during adolescence and young adulthood cognitive abilities. Next, we used multilevel models to test whether these relations reflect between- and/or within-twin pair associations.

Results Phenotypically, cannabis use was related to poorer cognitive functioning, although most associations were negligible after accounting for other substance use. Nevertheless, there were few significant within-family twin-specific associations, except that age 17 cannabis frequency was associated with worse age 23 Common EF and general cognitive ability.

Conclusions We found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users.

Keywords: cannabisintelligenceexecutive controladolescenceyoung adulthood

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An alternative strategy is to use monozygotic (MZ) twins discordant for various indices of
cannabis use, which controls for all genetic and shared environmental confounds as well as age, sex, cohort, and parental characteristics. Additionally, same-sex dizygotic (DZ) twins discordant for cannabis will control for all shared environmental confounds, age, sex, cohort, and parental characteristics, but only partially for genetic differences between families. To our knowledge, there have been three studies using this design to address the association between cannabis use and cognition. However, there has been extensive research using this design to examine causal associations with alcohol (Kendler et al., 2000; Prescott et al., 1999; Young-Wolffe et al., 2011). We choose to use the discordant twin design so that we can compare our results directly with previous studies on the association between cannabis use and cognition.

First, Lyons et al. (2004) examined MZ twins discordant for use 20 years after regular use, and found a significant difference between twins on only one of 50+ measures of cognition. Second, Jackson et al. (2014) found no evidence for a dose-dependent relationship or significant differences in cognition among MZ twins discordant for cannabis use. Similarly, Meier et al. (2017) found no evidence for differences in cognition among a combined sample of MZ and DZ twins discordant for cannabis dependence or use frequency. Thus, quasi-experimental, co-twin control designs have yielded little evidence that cannabis causes poorer cognition.

We expanded on these previous studies in several ways. First, we evaluated the association
between cannabis use and EFs in addition to intelligence; specifically, we examined three EF
components with factor scores derived from a well-validated latent variable model (Friedman et al., 2016; Miyake et al., 2000; Miyake and Friedman, 2012). Most of the discordant twin studies of the association between cannabis use and cognition have focused on general cognitive ability, not on EF. Second, we also considered whether cannabis–cognition associations are explained by other substance use, given the high frequency of polysubstance use (Kedia et al., 2007). Third, we assessed participants during adolescence and young adulthood, while the above-mentioned studies focused on twins up to age 20 and older than age 45.