The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial

Pharmacogenomics J. 2004;4(3):184-92. doi: 10.1038/sj.tpj.6500238.


To determine whether the functional mu-opioid receptor (OPRM1) Asn40Asp variant predicts the comparative efficacy of different forms of NRT, we conducted a clinical trial of transdermal nicotine (TN) vs nicotine nasal spray (NS) in 320 smokers of European ancestry. Smokers carrying the OPRM1 Asp40 variant (n=82) were significantly more likely than those homozygous for the Asn40 variant (n=238) to be abstinent at the end of treatment, and reported less mood disturbance and weight gain. The genotype effect on treatment outcome was most pronounced among smokers receiving TN, particularly during the 21 mg dose phase. Smokers who carry the OPRM1 Asp40 variant are likely to have a favorable response to TN and may benefit from extended therapy with the 21 mg dose.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Cutaneous
  • Administration, Intranasal
  • Adult
  • Asparagine / genetics
  • Aspartic Acid / genetics
  • Female
  • Follow-Up Studies
  • Genetic Variation / drug effects
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage*
  • Predictive Value of Tests
  • Receptors, Opioid, mu / genetics*
  • Smoking / drug therapy*
  • Smoking / genetics*
  • Time Factors


  • OPRM1 protein, human
  • Receptors, Opioid, mu
  • Aspartic Acid
  • Nicotine
  • Asparagine