Cannabis and Depression: Unraveling the Brain's Hidden Connections

Although behavioral and epidemiological studies demonstrate high co-morbidity between cannabis use and depression, the underlying neurobiological mechanisms of this relationship remain poorly understood. This study evaluated the interaction between cannabis use and depression on brain resting state functional connectivity using graph theory network properties in 223 individuals who currently use cannabis (26.8 ± 8.1 years, 61.9 % males) and 172 controls (25.0 ± 6.8 years, 48.3 % males). Graph theory analyses showed that the cannabis group relative to the control group had shorter characteristic path length, higher global efficiency and transitivity as well as increased local efficiency and clustering coefficient in salience, frontoparietal, and subcortical networks. Depression symptoms significantly moderated the effect of group on global measures, such that the effect of cannabis use status on characteristic path length, global efficiency and transitivity weakened in those with higher depression scores. Post-hoc analyses indicated a dose-response relationship such that the higher cannabis use frequency, the shorter characteristic path length, higher global efficiency, and transitivity; but no significant moderating effect of depression symptoms emerged on these associations. These findings suggest that the co-occurrence of depression symptoms and cannabis use, compared to cannabis use alone, may be associated with less efficient and less integrated brain network function. Among those who use cannabis, the effects of cannabis use frequency on these global measures do not vary with depression symptoms, suggesting that depression's moderating effect is conditional on cannabis use status, not dose. These findings underscore the complex interplay between cannabis use and depression in altering functional brain organization.