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

Tracy Brown, Che Liu, Emese Kroon, Janna Cousijn, Francesca Filbey

DOI: 10.64898/2026.03.10.26348038 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cross-sectional study
Sample size 119
Population Adults who use cannabis near-daily (68 men; Mage=22.66, SE=.31)
Measures resting-state functional connectivity (rsFC) of the default mode network (DMN)
Topics Cannabis Default mode network
Key findings Pain frequency interacts with cannabis use to affect DMN connectivity: more frequent pain was negatively associated with weekly use or years of use in l-IPL-PCC and r-IPL-PCC rsFC, but positively associated with daily grams in l-IPL-r-IPL and r-IPL-PCC rsFC (BH-FDR-corrected p<.05).

Abstract

Abstract Background Chronic 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 brain’s 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.

Methods: We 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.

Results: Results 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).

Conclusions: First, 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.