Acute and Chronic Effects of Cannabis on the Neural Correlates of Working Memory in Adolescents versus Adults

Background: Previous research suggests that cannabis affects the adult working memory circuit, a neural network which undergoes significant development during adolescence. It is therefore intuitive to hypothesise that adolescents may be more vulnerable to the effects of cannabis during this neurodevelopmental window. This is especially noteworthy as national demographics suggest adolescents use cannabis more than adults. Research is therefore needed to determine how adolescent working memory is affected by cannabis both acutely and chronically compared to adults. Secondly, current research is unclear on whether CBD exacerbates or dampens cognitive impairment effects. Therefore, exploratory research is needed to investigate if THC+CBD cannabis produces different effects to THC-only cannabis.
Methods: Chronic: A longitudinal study with two timepoints, one year apart, recruited 140 participants; 35 adolescents and 35 adults who use cannabis, plus 35 adolescent and 35 adult controls. All adults were aged 26-29yrs and adolescents 16-17yrs. At both timepoints, participants completed the spatial N-back task during an fMRI scan to assess working memory change across one year. Acute: In a within-subjects, blinded, repeated-measure study, 24 adults and 24 adolescents attended 3 testing sessions to complete the spatial N-back task in an fMRI scanner to examine working memory function. Before the task, all participants were administered; placebo on visit 1, THC+CBD cannabis on visit 2, and THC-only cannabis on visit 3.
Results and Conclusions:  Analysis is currently being conducted. Results and conclusion will be available at conference. ANOVA analyses will be performed to assess group differences for the task i) behavioural performance, comparing reaction time and d-prime as a measure of accuracy, and ii) associated neural activity via wholebrain analysis and ROI working memory network analysis using a Neurosynth mask. Our hypotheses are:
1. Chronic: Participants who use cannabis will show worsened behavioural working memory performance vs controls.
2. Chronic: Participants who use cannabis will show altered wholebrain and working memory network activation vs controls when examined; i) overall across timepoints ii) via change-score for the activation patterns after one year. Difference in neural activation vs age-matched controls will be more pronounced in adolescents vs adults.
3. Acute: Cannabis administration will be associated with increased reaction times and decreased accuracy during the task. This will be different for THC-only vs THC+CBD cannabis conditions, and adolescents who use cannabis will show larger performance impairment than adults who use cannabis.
4. Acute: Adults and adolescents will show different neural activation patterns during the task when cannabis is administered vs placebo. This difference will be greater for adolescents vs adults. Lastly, THC-only and THC+CBD cannabis conditions will be associated with different activation patterns.