Regional brain [11C]carfentanil binding following tobacco smoking

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 [11C]carfentanil binding after tobacco smoking. 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, [11C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans. Smoking avnic cigarette decreased the binding potential (BPND) of [11C]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 BPND 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 BPND compared to after denic smoking in most brain areas listed above. However in the *G carriers the significant BPND 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. The present study demonstrates that BPND 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. •Authors found that average nicotine (avnic) cigarette smoking decreases [11C]carfentanil binding potentials (BPND) in several regional brain areas among overnight abstinent male tobacco smokers.•In the OPRM1 AA allele carriers, avnic cigarettes significantly changed BPND compared to after denicotinized (denic) smoking in the several regional brain regions.•For the OPRM1 *G carriers the significant BPND changes were confirmed in only limited brain areas compared to the AA carriers.•The *G allele carriers had fewer free brain mu opioid receptor availability than the AA carriers in left amygdala and left nucleus accumbens.