Impact of year-long cannabis use for medical symptoms on brain activation during cognitive processes

Abstract

Importance: Cannabis is increasingly being used to treat medical symptoms, but the effects of cannabis use on brain function in those using cannabis for these symptoms is not known.

Objective: To test whether brain activation during working memory, reward, and inhibitory control tasks, areas of cognition impacted by cannabis, showed increases following one year of cannabis use for medical symptoms.

Design: This observational cohort study took place from July 2017 to July 2020 and is reported on in 2024.

Setting: Participants were from the greater Boston area.

Participants: Participants were recruited as part of a clinical trial based on seeking medical cannabis cards for anxiety, depression, pain, or sleep disorders, and were between 18 and 65 years. Exclusion criteria were daily cannabis use and cannabis use disorder at baseline.

Main outcomes and measures: Outcomes were whole brain functional activation during tasks involving working memory, reward and inhibitory control at baseline and after one year of cannabis use.

Results: Imaging was collected in participants before and one year after obtaining medical cannabis cards; 57 at baseline (38 female [66.7%]; mean [SD] age, 38.0 [14.6] years) at baseline, and 54 at one-year (37 female [68.5%]; mean [SD] age, 38.7 [14.3] years). Imaging was also collected in 32 healthy control participants (22 female [68.8%]; mean [SD] age, 33.8 [11.8] years) at baseline. In all groups and at both time points, functional imaging revealed canonical activations of the probed cognitive processes. No statistically significant difference in brain activation between the two timepoints (baseline and one-year) in those with medical cannabis cards and no association of changes in cannabis use frequency with brain activation were found.

Conclusions and relevance: Findings suggest that adults do not show significant neural effects in the areas of cognition of working memory, reward, and inhibitory control after one year of cannabis use for medical symptoms. The results warrant further studies that probe effects of cannabis at higher doses, with greater frequency, in younger age groups, and with larger, more diverse cohorts.

Trial registration: NCT03224468, https://clinicaltrials.gov/.

Figure 1:. Brain activation for the N-back task’s two-back vs. zero-back contrast across groups and timepoints

The HC group at baseline (n=22), the MCC group at baseline (n=40), and the MCC group at one-year (n=40) did not show activation differences between the two groups at baseline or between the two time points of the MCC group. Cannabis use frequency changes were not associated with brain activation at one-year. Figure 1a: Voxel-wise average brain activation, colored by effect size and opacity-scaled by z-scores with significance threshold (FDR=0.05) outlined, for the two-back vs. zero-back contrast of the N-back task. z-thresholds: HC group at baseline=3.05; MCC group at baseline=2.47, and MCC at one-year=2.60. Colorbar displays effect size. Figure 1b: Grayordinate-wise average brain activation z-scores above significance threshold (FDR=0.05) for the two-back vs. zero-back contrast of the N-back task. z-thresholds: HC group at baseline=2.60), MCC group at baseline=2.21, and MCC at one-year=2.35. Colorbar displays z-scores. HC=healthy control; MCC=medical cannabis card.

Figure 2:. Brain activation for various contrasts of the MID task across groups and timepoints

The HC group at baseline (n=23), the MCC group at baseline (n=35), and the MCC group at one-year (n=40; except High Loss vs. Neutral Hit: n=39) did not show activation differences between the two groups at baseline or between the two time points of the MCC group. Cannabis use frequency changes were not associated with brain activation at one-year. Figure 2a: Voxel-wise average brain activation, colored by effect size and opacity-scaled by z-scores with significance threshold (FDR=0.05) outlined, for the high reward cue vs. baseline contrast (top row) and the high loss vs. neutral hit feedback contrast (bottom row) of the MID task. z-thresholds: HC group at baseline=3.37 (top) and undetermined (bottom), MCC group at baseline=3.24 (top) and 4.34 (bottom), and MCC at one-year=3.10 (top) and 4.65 (bottom). Note that activation for the other contrasts was below threshold. Colorbar displays effect size. Undetermined z-threshold indicates that no voxel was statistically significant. Figure 2b: Grayordinate-wise average brain activation z-scores above significance threshold (FDR=0.05) for the high reward cue vs. baseline contrast of the MID task. z-thresholds: HC group at baseline=2.91, MCC group at baseline=2.74, and MCC at one-year=2.70. Note that activation for the other contrasts was below threshold. Colorbar displays z-scores. HC=healthy control; MCC=medical cannabis card.

Figure 3:. Brain activation for the SST task’s two STOP vs. GO contrasts across groups and timepoints

The HC group at baseline (n=25), the MCC group at baseline (n=40), and the MCC group at one-year (n=44) did not show activation differences between the two groups at baseline or between the two time points of the MCC group. Cannabis use frequency changes were not associated with brain activation at one-year. Figure 3a: Voxel-wise average brain activation, colored by effect size and opacity-scaled by z-scores with significance threshold (FDR=0.05) outlined, for the successful STOP vs. GO contrast (top row) and the unsuccessful STOP vs. GO contrast (bottom row) for the SST task. z-thresholds: HC group at baseline=2.77 (top) and 2.87 (bottom); MCC group at baseline=2.56 (top) and 2.62 (bottom), and MCC at one-year=2.62 (top) and 2.55 (bottom). Colorbar displays effect size. Figure 3b: Grayordinate-wise average brain activation z-scores above significance threshold (FDR=0.05) for the successful STOP vs. GO contrast (top row) and the unsuccessful STOP vs. GO contrast (bottom row) for the SST task. z-thresholds: HC group at baseline=2.25 (top) and 2.31 (bottom); MCC group at baseline=2.15 (top) and 2.20 (bottom), and MCC at one-year=2.22 (top) and 2.13 (bottom). Colorbar displays z-scores. HC=healthy control; MCC=medical cannabis card.