Mu-opioid receptor availability in patients with opioid use disorder treated with either methadone or buprenorphine

Methadone (MET) and buprenorphine (BUP)—mu-opioid receptor (MOR) agonists—are efficacious treatments for opioid use disorder (OUD). Using high-sensitivity, long axial field-of-view PET imaging with [ ¹¹ C]carfentanil, we compared MOR availability in 5 MET and 5 BUP patients and 13 healthy controls (HCs) in five brain regions: ventral tegmentum, thalamus, caudate, putamen, and amygdala. MOR availability differed across groups (F _10,34 =5.6, p<0.001) and was lower in BUP patients than HCs across all brain regions (mean reduction=39.1±15.2%; p<0.001), lower in MET patients than HCs in the ventral tegmentum and amygdala (p’s<0.05), and lower in BUP than MET patients in four of five regions (p’s<0.05). MOR availability was inversely related to serum drug levels, linear for MET (R²=0.83, linear) and logarithmic for BUP (R²=0.96). [ ¹¹ C]carfentanil PET may be useful in guiding personalized OUD treatment based on receptor engagement, which differs significantly between the two opioid agonist treatments. Studies are needed to link MOR availability with specific clinical characteristics (e.g., hedonic capacity, MOR agonist-associated weight gain) and OUD treatment outcomes.