Preliminary evidence of neuroimmune system disruption in opioid use disorder: Findings from a pilot PET TSPO imaging...

Preclinical and postmortem human studies demonstrate significant opioid-related alterations in the neuroimmune system. However, studies investigating the neuroimmune system in living people with opioid use disorder (OUD) are lacking, thereby motivating this pilot study.

Individuals with OUD (n = 6; DSM-5 criteria) were admitted inpatient and stabilized on an individualized buprenorphine dose for 5 to 10 days before a 120-min Positron Emission Tomography (PET) [¹¹C]PBR28 scan. Using multilinear analysis-1 (MA-1; t* = 30), total volume of distribution (V _T; 'TSPO availability') was estimated in 10 brain regions of interest (ROIs) incorporating the metabolite-corrected arterial input function. Demographically-matched non-OUD comparators (n = 18) underwent identical PET imaging procedures. Group differences in regional [¹¹C]PBR28 V _T were evaluated using linear mixed effects models. Partial correlations, controlling for rs6971 genotype, investigated relationships between regional [¹¹C]PBR28 V _T and subjective, behavioral, and biomarker data.

OUD participants exhibited higher brain TSPO availability by 20% across ROIs, on average (range: 12-22%) relative to non-OUD comparators (Group Effect; p = 0.036) whereas plasma cytokine/chemokine levels did not differ (ps > 0.05). Greater opioid craving correlated with higher TSPO availability in the parietal (r=0.82, p = 0.048) and prefrontal cortices (r=0.80, p = 0.059). Longer treatment duration correlated with lower TSPO availability in the prefrontal cortex (r = -0.93, p = 0.024).

Results are the first exploratory evidence that living participants with OUD, stabilized on buprenorphine inpatient, exhibit elevated TSPO availability, an in vivo neuroimmune marker. TSPO availability was positively correlated with opioid craving and negatively correlated with treatment duration. While preliminary, our findings suggest that the neuroimmune system may be a therapeutic target in OUD.