Regional Brain [(11)C]carfentanil Binding Following Tobacco Smoking

OBJECTIVE: To determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco smoking. METHODS: Twenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [(11)C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans. RESULTS: Smoking avnic cigarette decreased the binding potential (BP(ND)) of [(11)C]carfentanil in the right medial prefrontal cortex (mPfc; 6,56,18), left anterior medial prefrontal cortex (amPfc; −2,46,44), right ventral striatum (vStr; 16, 3, −10), left insula (Ins; −42,10, −12), right hippocampus (Hippo; 18, −6, −14) and left cerebellum (Cbl; −10, −88, −34), and increased the BP(ND) in left amygdala (Amy; −20,0, −22), left putamen (Put; −22, 10, −6) and left nucleus accumbens (NAcc; −10,12, −8). In the AA allele carriers, avnic cigarette smoking significantly changed the BP(ND) compared to after denic smoking in most brain areas listed above. However in the *G carriers the significant BP(ND) changes were confirmed in only amPfc and vStr. Free mu opioid receptor availability was significantly less in the *G than the AA carriers in the Amy and NAcc. CONCLUSION: The present study demonstrates BP(ND) changes induced by avnic smoking in OPRM1 *G carriers were blunted compared to the AA carriers. Also *G smokers had less free mu opioid receptor availability in Amy and NAcc.