After year-long cannabis use for medical symptoms, we did not observe functional differences during working memory, reward processing, or inhibitory control tasks or an association of changes in cannabis use frequency with brain activation. Similarly, no significant changes in behavioral performance emerged. This suggests that cannabis use for medical purposes, within the snapshot of cognition captured by these tasks and within a mostly older, white, female and generally well-educated population, does not have a significant neural impact.

Prior studies have found that cannabis use, especially in adolescents, is associated with impairments in cognitive processes beyond acute intoxication.¹¹ Such studies have largely been cross-sectional, have generally not focused on adults using cannabis for medical purposes, and have focused primarily on heavy cannabis use. Further, conclusions of studies comparing individuals who use cannabis with those who do not often are limited by inherent group differences at the outset. Thus, the neural impact of cannabis use for medical purposes has remained largely unknown. Because participants in this study did not use cannabis heavily at baseline and obtained MCCs for the first time for their medical symptoms, the study was uniquely positioned to examine the brain before and after adults began to use cannabis regularly, a period that is difficult to capture. This study is one of the first studies to evaluate brain activation differences in an ecologically valid setting in those who began using cannabis for medical and psychological symptoms.

Memory is one of the most consistently reported processes that is affected by cannabis.³³ Prior studies comparing those who use cannabis to those who do not have found significant changes in activation of frontal regions during the N-back task,^34–37 though it should be noted that other studies did not report statistically significant difference in any regions.^38,39 Reward-related activation has also been implicated in cannabis use, as prior studies have found significant changes in activation of striatal regions during the MID task.^40–45 Finally, inhibitory control activation differences have been reported, ^46,47 particularly in fronto-basal-ganglia circuits.⁴⁸ However, these studies mainly consist of those who began using cannabis during adolescence or those who use cannabis frequently. Contrary to our initial hypothesis and this literature, our findings indicate that activation to working memory, reward processing, and inhibitory control tasks is largely unchanged in adults using cannabis to alleviate medical symptoms for one year. There are potential reasons for the lack of neural changes in this study compared to previous studies of recreational cannabis, including differences in use patterns, amounts, motivations for use, lower use in adolescence or other factors.

The findings of the study are corroborated by the results of the control group and by the brain activation patterns observed at both timepoints. Brain activation differences were not found between healthy controls and MCC participants at baseline, suggesting that the MCC group did not differ significantly at baseline from those who were not intending to use cannabis, thus addressing some of the limitations in previous studies. The working memory and inhibitory control tasks yielded statistically significant canonical activations in the control and MCC group at baseline and in the MCC group at the one-year timepoint.^20,28,48,49 The reward processing task also yielded canonical activations for the cue contrasts.^{28,29,32,50,51} Activations to the feedback contrasts were also in line with what has been observed in the past, though the literature is less consistent in regards to the feedback contrast.^29,50,51 Of note, only two of the MID contrasts reached statistical significance. This suggests that the response to the task was more heterogeneous in this participant sample, and perhaps a larger sample or a differently designed reward task would have been needed to achieve more robust activation. It was recently noted that the MID task has low reliability, with the most consistent contrasts being those involving an implicit baseline, which is consistent with our limited findings.⁵² Overall, the activation patterns of all three tasks were consistent with those observed in the literature, demonstrating that in the comparison across time, brain activation from the desired cognitive processes is being compared.