Track topics on Twitter Track topics that are important to you
- Central nicotinic acetylcholine receptors (nAChRs) are primary targets for the action of nicotine. In addition to being involved in tobacco dependence, they are also involved in a variety of brain disorders, including Alzheimer's and Parkinson's diseases. Researchers are interested in developing better ways to study the action of nAChRs to improve treatments for smoking cessation and other problems affected by these receptors. These new study methods may involve different approaches to positron emission tomography (PET) scanning, which can show brain activity related to nAChRs.
- To evaluate appropriate and useful doses of radiotracers used in PET scanning of nAChRs in the brains of nonsmokers/former smokers, light smokers, and heavy smokers.
- Individuals between 18 and 50 years of age who fall into one of the following groups: (1) nonsmokers or former smokers who have not smoked for the past 2 years, (2) light/situational smokers, or (3) heavy smokers (at least 15 cigarettes/day for the past 2 years).
- Each participant will undergo up to three PET studies, given approximately1 month apart. Each study will take approximately 8 hours to complete.
- Participants will provide urine and breath samples before the study and at the start of the study, which will be tested for chemicals that may interfere with the study.
- Depending on the study, some of the smoking participants may receive a nicotine patch to wear during the PET scan.
- On the day of the study, participants will receive a dose of a radiotracer (a drug used in PET scanning) given either as a single injection or as an injection followed by a continuous infusion, and will have a series of PET scans over the next 7 hours and provide blood samples during that time.
- Participants will return for a follow-up visit 1 month after the end of the study.
Background: Central nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain functions and have been implicated in the pathophysiology of Alzheimer's and Parkinson's diseases, other CNS disorders (Tourette's syndrome, epilepsy, etc.), and nicotine dependence. These receptors are the primary target for the action of nicotine, which is believed to cause tobacco dependence. The ability to quantitatively image nAChRs with PET in humans would allow scientists to monitor the nAChRs in vivo during nicotine dependence and smoking cessation and to determine the receptor occupancy by nicotine for different types of nicotine replacement therapy (NRT). Recently completed studies demonstrated the feasibility of imaging nAChRs in the human brain with 2[18F]FA-85380 and showed that each participant could receive up to 4 injections of 5 mCi/70 kg without exceeding dosimetry limits imposed by the FDA and the NIH Radiation Safety Committee.
Scientific Goal: The aims of the proposed study are 1) to compare the total volumes of distribution for 2[18F]FA-85380 and volumes of distribution for specific binding compartment (an estimate of nAChR densities) in brains of light and heavy smokers and 2) to develop a simplified PET procedure that is more comfortable for the human participants and that maintains the ability to accurately quantify nAChR binding in vivo.
Study Population: Healthy adult participants (non-smokers or exsmokers and light (situational) and heavy smokers), males and females between 18 and 50 years of age, will be recruited for this study. The goal is to complete studies of 12 controls (non-smokers or exsmokers), 12 light smokers and 12 heavy smokers.
Experimental Design and Method: After being medically cleared and giving informed consent, each participant will undergo up to three PET studies. In each study, the participant will receive a 5 mCi/70 kg dose of the radioligand, 2[18F]FA-85380-Injection. For one of the studies, the participants who smoke will receive nicotine by a nicotine patch (Nicoderm), applied approximately 4 h before the scan. The patch will be removed 12 h after it is applied. For two studies (one without and one with nicotine), participants who smoke will receive the radioligand as a bolus injection. Six of the participants who do not currently smoke (control group) will receive the radioligand as a bolus injection twice without nicotine either time. For the third study, all participants will receive the radioligand as a bolus injection followed by a continuous infusion (bolus injection/infusion combination). Six of the participants who do not currently smoke (control group) will receive the radioligand as a bolus plus infusion injection twice. For each study, a series of brain PET scans will be acquired for 8 h beginning at the time of the injection. The data from the PET scans without and with nicotine patch (smokers only) will be used to determine the total and non-specific accumulation of radioactivity in the brain. The data from the equivalent two PET scans for the controls will be used to determine the test-retest reliability of the measure. The data from the PET scans acquired from the bolus/infusion paradigm will be used to demonstrate the feasibility of a shorter scanning period for quantitation studies. It is anticipated that several of the participants will choose not to continue after the first scan. The study design accommodates this expectation.
Benefits to participants and/or society: This protocol will provide no direct benefits to the research participants other than routine medical screening and attention from the research staff. The knowledge gained in this study may lead to the availability of an agent for external monitoring of nAChRs using PET. This agent would be a valuable tool for determining the dynamics of nAChRs in nicotine dependence and smoking cessation.
Risks to participants: There are risks related to the PET scans in general, involving exposure to radiation, arterial catheterization and venous catheterization. In addition, there are risks related to the administration of this radiopharmaceutical and from exposure to nicotine. Medical supervision will be provided throughout the study. A plan for monitoring potential side effects of this radiotracer is given.
National Institute on Drug Abuse, Biomedical Research Center (BRC)
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-27T03:17:05-0400
The purpose of this research program is to understand how a biomarker called the "nicotine metabolite ratio" (also referred to as NMR) may influence a smoker's ability to quit smoking.
The purpose of this study is to evaluate the effect of a combination of the 21 mg nicotine patch and nicotine-free cigarette compared to 21 mg nicotine patch only and nicotine-free cigaret...
This study will examine the effects of combining Varenicline (VRN) and N-acetylcysteine (NAC) on neural circuitry function and treating nicotine addiction. Healthy adult nicotine dependent...
Nicotine is the most common drug of abuse in the United States, and has addiction strength comparable to cocaine, heroin, and alcohol. It is the primary addictive component of tobacco, and...
This is a 2-year study involving the progressive reduction in the nicotine content of cigarettes. The investigators believe that at the end of the study smokers of cigarettes with progress...
Despite the centrality of addiction in academic accounts of smoking, there is little research on smokers' beliefs about addiction to smoking, and the role of nicotine in tobacco dependence. Smokers' p...
Smoking is associated with significant morbidity and mortality. Understanding the neurobiology of the rewarding effects of nicotine promises to aid treatment development for nicotine dependence. Throu...
Nicotine harms adolescent brain development and contributes to addiction. Some adolescents report using nicotine-free e-cigarettes, but the accuracy of their reporting is unclear. We explored adolesce...
Combustible cigarettes remain the most harmful and addictive tobacco product, and reducing the prevalence of smoking continues to be a critical public health goal. While nicotine is the constituent pr...
Metabolism of nicotine has implications for addiction and may be altered in people with type 2 diabetes. Thus, our objective was to analyze nicotine metabolism in adults with and without type 2 diabet...
Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.
A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to DEPRESSION or DRUG ADDICTION.
A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.
A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)
The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase 'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...
Parkinson's is a progressive neurological condition, affecting one person in every 500, 95% of which are over 40. It is caused by degeneration of more than 70% of the substantia nigra, which depletes the dopamine (the neurotransmitter involved in pro...