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.

The authors have declared no competing interest.

Funding for this research was obtained through a grant, 1R01 DA042490, awarded to Francesca Filbey and Janna Cousijn from the National Institute on Drug Abuse/National Institute of Health.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of the University of Texas at Dallas and the Department of Psychology of the University of Amsterdam ethics committee approved this study.

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All data produced in the present study are available upon reasonable request to the authors