Effects of Nicotine on Brain Opioid Receptors

NCT01040338 | Terminated DMC

• 2 other identifiers: 809187R21DA027066
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nicotine Dependence

Keywords

Smoking; Tobacco; Nicotine; Dependence; Genetics

Outcome Measures

Primary Outcomes (1)

• MOR binding potential

  5/31/2011

Secondary Outcomes (1)

• Subjective reward/liking and cravings to smoke

  5/31/2011

Study Arms (2)

OPRM1 A118G AA genotype

Individuals with the AA genotype at the OPRM1 A118G polymorphism.

Drug: Nicotine

OPRM1 A118G AG or GG genotype

Individuals with the \*/G allele at the OPRM1 A118G polymorphism

Drug: Nicotine

Interventions

Nicotine DRUG

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.

OPRM1 A118G AA genotype; OPRM1 A118G AG or GG genotype

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

24 adult, non-treatment seeking smokers of European ancestry, reporting consumption of ≥10 cigarettes per day for at least the past 6 months.

You may qualify if:

• Non-treatment seeking smokers of European ancestry
• Between 18 and 50 years old
• Smoking at least 10 cigarettes per day for at least the past 6 months
• Able to provide informed consent
• Fluent, English-speaking
• Weight ≤ 300 lbs.

You may not qualify if:

• Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months
• Provide a Carbon Monoxide reading of ≤10 ppm at Medical screening.
• History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants)
• Current alcohol consumption that exceeds 25 standard drinks/week
• Providing a breath alcohol concentration (BAC) reading of \> 0.01 at any session.
• Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a urine pregnancy test at each session
• Women of child-bearing age must agree in writing to use an approved method of contraception
• History or current diagnosis of psychosis, major current depression or bipolar disorder, ADHD, schizophrenia, or any Axis 1 disorder as identified by the MINI
• Serious or unstable disease within the past 6 months (e.g., cancer \[except melanoma\], heart disease, HIV)
• History of epilepsy or a seizure disorder
• History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (\>100 beats/minute); history or current diagnosis of COPD, cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP\>150 or DBP\>90)
• Any medical or neurological condition that might interfere with the distribution of the radiotracer as determined by the study MD
• Current or past use (within past 12 months) of any medications containing naltrexone or other MOR antagonists (e.g., Revia, Trexan)
• Current use or recent discontinuation (within last 14-days) of the following medications
• Any form of smoking cessation medication (Zyban, Wellbutrin, Wellbutrin SR, Chantix, NRT)

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Center website

Biospecimen

Retention: SAMPLES WITH DNA

The samples that shall be collected for this study are as follows: 1. A 2ml saliva sample will be collected for DNA extraction using the Oragene™ kit at the Medical screening session for genetic analyses. 2. An additional saliva sample (\~ 5ml) will be also be collected at Medical screening and will be used to analyze baseline nicotine metabolites (i.e., cotinine and 3-hydroxycotinine). 3. All participants will provide two tubes of blood (10 ml each) to measure plasma estradiol \& cortisol levels before each PET scanning session. They will also provide two tubes of blood (10 ml each) at the end of the scan to measure plasma nicotine and cortisol levels.

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking

Interventions

Nicotine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Caryn Lerman, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2009
• First Posted: December 29, 2009
• Study Start: February 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: April 11, 2019

Record last verified: 2019-04

Locations

US (1)