The possible cooperation between hypnotizability-related and placebo mechanisms in pain modulation has not been consistently assessed. Here, we investigate possible genetic bases for such cooperation. The OPRM1 gene, which encodes the μ1 opioid receptor—the primary site of action for endogenous and exogenous opioids—is polymorphic in the general population for the missense mutation Asn40Asp (A118G, rs1799971). The minor allele 118G results in decreased levels of OPRM1 mRNA and protein. As a consequence, G carriers are less responsive to opioids. The aim of the study was to investigate whether hypnotizability is associated with the presence of the OPRM1 polymorphism. Forty-three high and 60 low hypnotizable individuals, as well as 162 controls, were genotyped for the A118G polymorphism of OPRM1. The frequency of the G allele was significantly higher in highs compared to both lows and controls. Findings suggest that an inefficient opioid system may be a distinctive characteristic of highs and that hypnotic assessment may predict lower responsiveness to opioids.