Effects of Nicotine on Brain Opioid Receptors

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Total Enrollment

15 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-02-28

Study Completion Date

2011-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Effects of Smoking on Opioid Receptor Binding: A PET Study

NCT00618631

Substance-related Discorder

COMPLETED PHASE1

Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers

NCT02250664

Tobacco Use Disorder

COMPLETED PHASE1/PHASE2

Genetic Effects on Dopamine Response to an Opiate

NCT01878006

Polymorphism-Genetic Pain Addiction

COMPLETED PHASE2

Oxytocin Treatment of Opioid Dependence

NCT02548728

Opioid Dependence Opioid Withdrawal

COMPLETED PHASE1/PHASE2

A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans

NCT02360371

Opioid Sensitivity Individual Difference Abuse Opioids

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Nicotine Dependence

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_CROSSOVER

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

OPRM1 A118G AA genotype

Individuals with the AA genotype at the OPRM1 A118G polymorphism.

Nicotine

Intervention Type 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 AG or GG genotype

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

Nicotine

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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)
* Recent (within last 2 weeks) or planned use of psychotropic medications (anti-psychotics, anti-depressants (tricyclic, SSRI, MAOI), anti-anxiety or panic medications, and stimulants (e.g., Provigil, Ritalin), and opiate-containing medications for chronic pain
* Allergic response to any form of opioids or naloxone
* Participants shall be instructed to refrain from using any study prohibited drugs (note - participants are allowed to take prescription medicines not in the exclusion list) throughout their participation in the study.
* Self-reported history of head trauma or prior seizure, brain (or CNS) tumor
* Self-reported history of claustrophobia (contraindicated for PET)
* Inability to complete the baseline study procedures within four hours and/or correctly, as determined by the principal investigator.

Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes