NCT01040338

Effects of Nicotine on Brain Opioid Receptors

Functional Characterization of OPRM1 A118G in Nicotine Dependence: IV Nicotine Study

• Status: Terminated
• Phase: —
• Study type: Observational
• Enrollment: 15 (actual)
• Sponsor: University of Pennsylvania · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

A substantial body of evidence implicates the endogenous opioid system, and the mu opioid receptor (MOR) in particular, in the reinforcing effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the mu opioid receptor gene (OPRM1 Asp40) is associated with the ability to quit smoking, as well as nicotine reward and withdrawal symptoms. However, the precise mechanism through which this SNP influences nicotine dependence remains unresolved. This positron emission tomography (PET) study will examine whether this OPRM1 SNP alters MOR binding in response to nicotine in human smokers. Specifically, we will use \[11 C\]carfentanil PET imaging to assess the effects of intravenous (IV) nicotine versus saline (within-subject) on MOR binding potential in 24 chronic smokers genotyped prospectively and stratified by OPRM1 genotype.

Detailed description

The study uses a mixed factorial design with one between subject factor (OPRM1 genotype\_: Asn40/Asn40 vs. Asn40/Asp40 or Asp40/Asp40) and one within-subject factor (IV nicotine vs. IV saline) to examine genotype by nicotine interactions on MOR binding potential (BP\_ND ) assessed via PET imaging with \[11 C\]carfentanil. Twenty-four smokers (12 male, 12 female; 12 from each genotype group) will participate in two 90 minute PET sessions following overnight (14-hours) abstinence from nicotine. Genotype groups will be matched for age and sex . One week prior to the first PET session, there will be an adaptation session during which participants will receive IV saline followed 30 minutes later by IV nicotine (1 mg/70 kg) to ensure that they tolerate the procedure. In the PET sessions, participants will receive either IV nicotine (1 mg/70 kg) or saline (within-subject, double blind, counterbalanced). The primary outcomes will be BP\_ND in ventral striatum and anterior cingulate cortex (ACC). Normally menstruating women will be scheduled for their sessions during the early follicular phase. Sessions will be separated by 1 month for all participants to reduce variability in MOR binding due to hormonal changes during females menstrual cycles. Participants will complete subjective measures of nicotine reward and craving at each session.

Conditions

• Nicotine Dependence

Interventions

Type	Name	Description
DRUG	Nicotine	Participants shall receive an intravenous injection of nicotine during their practice session and one of their PET scans (double-blind). The dose of IV nicotine will be 1mg/70kg and the maximum dose that shall be injected is 1.2mg.

Timeline

• Start date: 2010-02-01
• Primary completion: 2011-03-01
• Completion: 2011-03-01
• First posted: 2009-12-29
• Last updated: 2019-04-11

Locations

1 site across 1 country: United States