Multiple lines of evidence implicate MORs in analgesia following placebo and acupuncture treatments. No study has examined the differential effects of these two interventions on binding of central MORs in chronic pain patients. We investigated the relationship between changes in MOR availability following acupuncture and sham acupuncture and subsequent changes in clinical pain. 18 female FM patients (ages 18-75) were randomized to receive either one acupuncture (n=9) or one sham acupuncture (n=9) treatment. Acupuncture treatment involved insertion of 9 sterile single-use acupuncture needles into the body whereas sham treatment did not involve skin penetration. Prior to and during treatment, all subjects underwent a 90 minute 11C-carfentanil positron emission tomography (PET) scan with needle insertion occurring at 40 minutes. Clinical pain was assessed pre- and post-treatment with the Gracely Box Scale (GBS). PET images were processed with Logan plot analysis resulting in maps of whole-brain MOR binding potential (BP). Correlations between changes in clinical pain and MOR BP were performed using SPSS v14.0. The acupuncture group displayed slightly greater reductions in clinical pain, but this was not statistically different between groups (mean difference pre-post+SD: acu=1.4+4.7; sham=0.3+2.8; p=0.54). Within the right inferior insula and right nucleus accumbens, MOR BP increased following acupuncture but not sham acupuncture (BP mean difference pre-post+SD: insula acu=-0.36+0.30, sham=-0.07+0.25; p=0.04; accumbens acu=-0.45+0.52, sham=-0.05+16; p=0.04). Changes in clinical pain were positively correlated with changes MOR BP in the insula (r=0.70; p=0.04) and accumbens (r=0.76; p=0.02) in the acupuncture but not the sham group (insula r=-0.47; p=0.24; accumbens r=0.06; p=0.89). There are differential effects of acupuncture and sham acupuncture on MOR BP in chronic pain patients, and these effects are associated with acupuncture efficacy.