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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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This study will evaluate effects of smoking on the dopaminergic system by using PET tomography with new radioligand, [11C]-(+)-PHNO. Our primary hypothesis is that smoking a cigarette will produce dopamine release and this release can be measured using PET imaging and the [11C]-(+)-PHNO radiotracer. The secondary hypothesis is that this smoking induced dopamine release will be correlated with subjective craving and anxiety ratings.
This will be a within-subjects study in healthy male and female smokers. There will be one within factor condition: Smoking and Non Smoking. Therefore, there will be a repeated measure of PET scans using [11C]-(+)-PHNO under two different conditions. Ten subjects (n=5 male and n=5 female) included in the study will come on two different days and will have a Smoking or Non smoking session performed just before the PET study. Subjective assessments will be conducted at each experimental condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy smokers | Healthy male and female smokers. Each subject will undergo PET scan (along with craving and anxiety questionnaires) on two conditions - Smoking and Non-smoking - on two separate visits. |
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| Measure | Description | Time Frame |
|---|---|---|
| [11C]-(+)-PHNO binding potential | The process of imaging requires the injection of a positron-emitting radiotracer (here, [11C]-(+)-PHNO) that binds to the protein of interest (here, dopamine receptor DRD2/3) followed by the measurement of this binding using the PET scanner. Dopamine release increases DRD 2/3 occcupancy which results in decreased radiotracer's binding potential, and vice versa. [11C]-(+)-PHNO binding potential will be measured on two different conditions (Smoking vs. Non-smoking) on two separate days. | Up to 14 days between PET scans |
| Measure | Description | Time Frame |
|---|---|---|
| Subjective reports of craving | Levels of subjective craving will be assessed prior to and after each condition (Smoking vs. Non-smoking) on two separate days. Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, The Urge to Smoke scale, Tobacco Craving Questionnaire, and 21-item Visual Analogue Scale will be used. | Up to 14 days between PET scans |
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Inclusion Criteria:
Exclusion Criteria:
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Healthy smokers
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| Name | Affiliation | Role |
|---|---|---|
| Bernard Le Foll, MD | Centre for Addiction and Mental Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Addiction and Mental Health - 33 Russell St | Toronto | Ontario | M5S 2S1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15229053 | Background | Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, Hahn EL, Mandelkern MA. Smoking-induced ventral striatum dopamine release. Am J Psychiatry. 2004 Jul;161(7):1211-8. doi: 10.1176/appi.ajp.161.7.1211. | |
| 15943487 | Background | Wilson AA, McCormick P, Kapur S, Willeit M, Garcia A, Hussey D, Houle S, Seeman P, Ginovart N. Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. J Med Chem. 2005 Jun 16;48(12):4153-60. doi: 10.1021/jm050155n. |
| Label | URL |
|---|---|
| Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching | View source |
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| ID | Term |
|---|---|
| D014029 | Tobacco Use Disorder |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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Whole blood (15mL)
| Subjective reports of anxiety | Subjective reports of anxiety will be collected prior to and after each condition (Smoking vs. Non-smoking) on two separate days. State anxiety questions from the Spielberg State-Trait Anxiety Inventory will be used. | Up to 14 days between PET scans |
| 15963538 | Background | Le Foll B, Goldberg SR, Sokoloff P. The dopamine D3 receptor and drug dependence: effects on reward or beyond? Neuropharmacology. 2005 Sep;49(4):525-41. doi: 10.1016/j.neuropharm.2005.04.022. |
| 10881212 | Background | Le Foll B, Schwartz JC, Sokoloff P. Dopamine D3 receptor agents as potential new medications for drug addiction. Eur Psychiatry. 2000 Mar;15(2):140-6. doi: 10.1016/s0924-9338(00)00219-4. |
| 17155853 | Background | Le Foll B, Goldberg SR, Sokoloff P. Dopamine D3 receptor ligands for the treatment of tobacco dependence. Expert Opin Investig Drugs. 2007 Jan;16(1):45-57. doi: 10.1517/13543784.16.1.45. |
| 16818870 | Background | Brody AL, Mandelkern MA, Olmstead RE, Scheibal D, Hahn E, Shiraga S, Zamora-Paja E, Farahi J, Saxena S, London ED, McCracken JT. Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry. 2006 Jul;63(7):808-16. doi: 10.1001/archpsyc.63.7.808. |
| 19153147 | Background | Boileau I, Guttman M, Rusjan P, Adams JR, Houle S, Tong J, Hornykiewicz O, Furukawa Y, Wilson AA, Kapur S, Kish SJ. Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in drug-naive Parkinson's disease. Brain. 2009 May;132(Pt 5):1366-75. doi: 10.1093/brain/awn337. Epub 2009 Jan 19. |