Year-Long Cannabis Use for Medical Symptoms and Brain Activation During Cognitive Processes

Abstract

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

Objective: To test whether 1 year of cannabis use for medical symptoms after obtaining a medical cannabis card was associated with increased brain activation during working memory, reward, and inhibitory control tasks, areas of cognition affected by cannabis.

Design, setting, and participants: This cohort study was conducted from July 2017 to July 2020 among participants from the greater Boston area who were recruited as part of a clinical trial of individuals seeking medical cannabis cards for anxiety, depression, pain, or insomnia symptoms. Participants were aged between 18 and 65 years. Exclusion criteria were daily cannabis use and cannabis use disorder at baseline. Data analysis was conducted from August 2021 to April 2024.

Main outcomes and measures: Outcomes were whole brain functional activation during tasks involving working memory, reward, and inhibitory control at baseline and after 1 year of medical cannabis card ownership.

Results: Imaging was collected from participants before and 1 year after obtaining medical cannabis cards, with 57 participants at baseline (38 female [66.7%]; 6 [10.5%] Black and 45 [78.9%] White participants; 1 [1.8%] Hispanic participant; median [IQR] age, 34.0 [24.0-51.0] years) and 54 participants at 1 year (37 female [68.5%]; 4 [7.4%] Black and 48 [88.9%] White participants; 1 [1.9%] Hispanic participant, median [IQR] age, 36.5 [25.0-51.0] years). Imaging was also collected in 32 healthy control participants at baseline (22 female [68.8%]; 2 [6.2%] Black and 27 [84.4%] White participants; 3 [9.4%] Hispanic participants; median [IQR] age, 33.0 [24.8-38.2] years). 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 2 time points (baseline and 1 year) in those with medical cannabis cards and no associations between changes in cannabis use frequency and brain activation after 1 year were found.

Conclusions and relevance: In this cohort study of adults obtaining medical cannabis cards for medical symptoms, no significant association between brain activation in the areas of cognition of working memory, reward, and inhibitory control and 1 year of cannabis use was observed. The results warrant further studies that probe the association of cannabis at higher doses, with greater frequency, in younger age groups, and with larger, more diverse cohorts.

Figure 1.. Brain Activation for the N-Back Task’s 2-Back vs 0-Back Contrast Across Groups and Time Points

The healthy control (HC) group at baseline (22 participants), the medical cannabis card (MCC) group at baseline (40 participants), and the MCC group at 1 year (40 participants) did not show activation differences between the 2 groups at baseline or between the 2 time points of the MCC group. Cannabis use frequency changes were not associated with brain activation at 1 year. Voxel-wise average brain activation, colored by effect size and opacity-scaled by z scores with the significance threshold (false-discovery rate P < .05) outlined, for the 2-back vs 0-back contrast of the N-back task. The z thresholds were 3.05 for the HC group at baseline, 2.47 for the MCC group at baseline, and 2.60 for the MCC group at 1 year. Color bar displays effect size.

Figure 2.. Brain Activation for the Monetary Incentive Delay Task’s High Reward Cue vs Baseline and High Loss vs Neutral Hit Contrast Across Groups and Time Points

The healthy control (HC) group at baseline (23 participants), the medical cannabis card (MCC) group at baseline (35 participants), and the MCC group at 1 year (40 participants, except high loss vs neutral hit, with 39 participants) did not show activation differences between the 2 groups at baseline or between the 2 time points of the MCC group. Cannabis use frequency changes were not associated with brain activation at 1 year. Voxel-wise average brain activation, colored by effect size and opacity-scaled by z scores with the significance threshold (false-discovery rate P < .05) outlined, for the high reward cue vs baseline contrast (A) and the high loss vs neutral hit feedback contrast (B) of the Monetary Incentive Delay task. The z thresholds were 3.37 for high reward and undetermined for high loss for the HC group at baseline, 3.24 for high reward and 4.34 for high loss for the MCC group at baseline, and 3.10 for high reward and 4.65 for high loss for the MCC group at 1 year. Note that activation for the other contrasts was below threshold. Color bar displays effect size. An undetermined z threshold indicates that no voxel was statistically significant.

Figure 3.. Brain Activation for the Stop Signal Task 2 Stop vs Go Contrasts Across Groups and Time Points

The healthy control (HC) group at baseline (25 participants), the medical cannabis card (MCC) group at baseline (40 participants), and the MCC group at 1 year (44 participants) did not show activation differences between the 2 groups at baseline or between the 2 time points of the MCC group. Cannabis use frequency changes were not associated with brain activation at 1 year. Voxel-wise average brain activation, colored by effect size and opacity-scaled by z scores with the significance threshold (false-discovery rate P < .05) outlined, for the successful stop vs go contrast (A) and the unsuccessful stop vs go contrast (B) for the Stop Signal Task. The z thresholds were 2.77 for successful stop vs go and 2.87 for unsuccessful stop vs go for the HC group at baseline, 2.56 for successful stop vs go and 2.62 for unsuccessful stop vs go for the MCC group at baseline, and 2.62 for successful stop vs go and 2.55 for unsuccessful stop vs go for the MCC group at 1 year. Color bar displays effect size.