The Role of Pain Frequency in the Divergent Associations Between Cannabis Use and Default Mode Network Connectivity

BackgroundChronic pain is one of the most common reasons for medicinal cannabis use, yet the neural mechanisms underlying cannabis-related modulation of pain remain poorly understood. Both pain and cannabis use independently alter functional connectivity within the brains default mode network (DMN) that modulate interoception and self-referential aspects of pain processing. The goal of this study was to examine the interaction between pain and cannabis use on DMN connectivity. MethodsWe measured DMN resting state fMRI functional connectivity (rsFC), past year pain frequency, and cannabis use measures (i.e., grams per day, days a week, years of regular use) from 119 adults who use cannabis near-daily (68 men; Mage= 22.66, SE= .31). Generalized linear models were used to test the main effects and interactions of pain frequency and cannabis use variables. ResultsResults indicated significant interactions between pain and cannabis use where more frequent pain was (1) negatively associated with weekly use or years of use in l-IPL-PCC and r-IPL-PCC rsFC, (2) whereas it was positively associated with daily grams of cannabis in l-IPL-r-IPL rsFC and r-IPL-PCC rsFC (BH-FDR-corrected p< .05). ConclusionsFirst, these findings demonstrate that pain frequency is a key context shaping the neurobiological correlates of exposure to cannabis. Second, divergent interaction effects suggest that, in the context of more frequent pain, cannabis use may relate to rsFC through distinct neural processes that depend on cumulative vs. proximal effects.