Clinical trial NCT01302262: Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans
Official title: Does the Insula Control Smoking-induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans. Part I: Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tobacco Use Disorder
Keywords: Smoking-induced dopamine release
[11C]-(+)-PHNO PET Study
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2011-02-24
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy smokers

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Adult males or females
* Regular smoking of at least 10 cigarettes, excluding ultra-low nicotine cigarettes, per day for at least two years
* Score on the Fagerstrom Test for Nicotine Dependence of 4 or more
* No intention to quit or reduce tobacco use, and no treatment for tobacco dependence currently
* No history of abuse of or dependence on any other drug, defined by DSM-IV criteria

Exclusion Criteria:

* Pregnancy
* Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning
* Claustrophobia
* Cardiovascular or cerebrovascular diseases
* Major psychiatric disorders including mood, anxiety or psychotic disorders
* History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor
* Gross structural brain abnormalities as revealed by T1 weighted images
* Current use or use during the previous month of medication that may affect the CNS (e.g. neuroleptics, bupropion)
* Learning disability, amnesia or other conditions that impede memory and attention

Primary outcomes:
measure: [11C]-(+)-PHNO binding potential
timeFrame: Up to 14 days between PET scans
Secondary outcomes:
measure: Subjective reports of craving
timeFrame: Up to 14 days between PET scans
measure: Subjective reports of anxiety
timeFrame: Up to 14 days between PET scans
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health - 33 Russell St
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Bernard Le Foll, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.