1. ¹Department of Psychiatry, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA
2. ²Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, USA
3. ³Molecular Diagnosis and Genotyping Facility, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA
4. ⁴Lombardi Cancer Center, Georgetown University, Washington, DC, USA
5. ⁵Statistical Genetics Unit, University of Alabama at Birmingham, Birmingham, AL, USA
6. ⁶Departments of Medicine, Psychiatry, and Biopharmaceutical Sciences, University of California San Francisco, San Francisco, USA

Correspondence: Dr C Lerman, University of Pennsylvania Transdisciplinary Tobacco Use Research Center, 3535 Market Street, Suite 4100, Philadelphia, PA 19104, USA. Tel: +1 215 746 7141; Fax: +1 215 746 7140; E-mail: clerman@mail.med.upenn.edu

Received 25 November 2003; Accepted 10 December 2003; Published online 9 March 2004.

Abstract

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.