A Brain Imaging Study Into Nicotine Induced Dopamine Release in Cigarette Smokers.

Tobacco Use Disorder Clinical Trial

Official title:

A Brain Imaging Study Into Nicotine Induced Dopamine Release in Cigarette Smokers, Using 11 C Raclopride in Positron Emission Tomography (PET)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00396669
• Other study ID #: 291006 HMO-CTIL
• Status: Recruiting
• Phase: N/A
• First received: November 6, 2006
• Last updated: March 26, 2012
• Start date: July 2007
• Est. completion date: July 2012

Study information

• Verified date: March 2012
• Source: Hadassah Medical Organization
• Contact: Aviv M Weinstein, Ph.D
• Phone: 00 972 2 6776705
• Email: avivweinstein[@]yahoo.com
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Dopamine (DA) plays a critical role in nicotine (and other) addiction and this drug is known to release DA in brain areas mediating reward and motivational processes. Although imaging studies show that release of DA follows smoking, little is known regarding how common genetic polymorphisms for three genes associated in some studies with smoking (dopamine D2 receptor, dopamine and serotonin transporter) interact with smoking status and modulate individual differences in nicotine-induced DA release and dopamine receptor occupancy, in vivo. The current proposal combines brain imaging and genomics ('imaging genomics') towards partially unraveling the complex relationship between smoking phenotype and common polymorphisms. Understanding whether genetic factors contribute to inter-individual variability in smoking is crucial for interpreting imaging results in the context of disease pathology. We hypothesize that a model of vulnerability to addiction based on interactions between genotype, receptor and transporter availability and in vivo nicotine-induced DA release will elucidate some of the fundamental neurochemical and neurogenetic circuits underlying addiction.

Description:

Dopamine plays a critical role in nicotine(and other) addiction and this drug is known to release DA in brain areas mediating reward and motivational processes. Although imaging studies show that release of DA follows smoking, little is known regarding how common some genetic polymorphisms proposed to play a role in nicotine dependence (e.g. DRD2, DAT and the serotonin transporter or SERT) interact with smoking status (non-smoker, ex-smoker, light smoker, present smoker) and modulate individual differences in nicotine-induced DA release and dopamine receptor occupancy, in vivo. Individual differences in dopaminergic tone could result in an under-stimulation of reward circuits which could put subjects at greater risk for seeking drug stimulation (that releases DA) as a means to compensate for this deficit and to temporarily activate these reward circuits. The current proposal combines brain imaging and genomics towards unraveling the complex relationship between smoking phenotype and common polymorphisms. Understanding whether genetic factors contribute to inter-individual variability is crucial for interpreting imaging results in the context of disease pathology.

Nicotine dependence is a complex process including initiation of smoking, persistence and difficulty in quitting. By comparing receptor occupancy, nicotine-induced DA release, and common genetic polymorphisms across smoking behaviors we will better understand the complex interactions between genetic makeup, personality and the several stages of nicotine addiction.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 50 Years

Eligibility

Inclusion Criteria:

• smokers who smoked 15 cigarettes/day and who met the DSM-IV criteria for nicotine dependence

Exclusion Criteria:

• Subjects who are diagnosed as suffering from psychotic illness according to DSM-IV (Axis 1)22, or with a history of CNS disease, a history of infection that might affect CNS (HIV, syphilis, cytomegalovirus, herpes), or a history of head injury with loss of consciousness will be excluded.

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Tobacco Use Disorder

Intervention

Drug:
• Bupropion
We measure dopamine release at the striatum using 11 C Raclopride at baseline and after smoking a cigarette
• Bupropion
Brain imaging after treatment with Bupropion

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dopamine D2 receptor occupancy before and after smoking a cigarette with nicotine		30 minutes	No
Secondary	Subjective measures of craving, anxiety and depression.		30 minutes	No