Nicotine Metabolizers and [11C]-(+)-PHNO (MET)

Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers

The purpose of this study is to investigate the effects of nicotine metabolism on occupancy of [11C]-(+)-PHNO to DA 2/3 receptors in different brain areas during periods of abstinence and smoking during an abstinence. This will be a Positron Emission Tomography (PET) study and the radiotracer [11C]-(+)-PHNO (11C]-( + )-4-propyl- 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol) will be used.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Other: cigarette

Detailed Description

The participants will undergo a PET scan after approximately 48 hours abstinence (to ensure total elimination of nicotine in both FMs and SMs) and then approximately >5 hours later may have a second PET scan after smoking their preferred cigarette (approximately 1 hour before). It is possible that these two scans may also occur on separate days. All subjects will provide a urine sample for (1) drug toxicology, (2) pregnancy test (in females) and (3) Total Nicotine Equivalents (TNE: a measure of total consumption unaltered by rate of nicotine metabolism). There will one blood draw taken before and one after each PET scan (about 20mls in total) to measure nicotine and COT levels (to assess abstinence) as well as kinetics of nicotine delivery. Participants will be given questionnaires prior to, or during, and/or after one or both of the PET scans to determine differences between abstinence and smoking on subjective measures..

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 1S8
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females of any ethnic origin 18 years of age or older.
• No previous use of medication for smoking cessation in previous month-
• Non-treatment seeker
• Either SMs or FMs by NMR

Exclusion Criteria:

• DSM-IV diagnosis of other drug dependences
• Any medical condition requiring immediate investigation or treatment
• Pregnancy tested by urine or lactation by self-report
• Current diagnosis of any Axis I psychiatric disorder
• Regular use of any therapeutic or recreational psychoactive drug use that may interfere with PET scanning
• Exposure to radiation in the last 12 months exceding permissible limit for participants participating in research
• Current use of medication that may interfere with [11C]-(+)-PHNO
• Metal implants or paramagnetic objects within the body which may interfere with the MRI
• Claustrophobia or a history of panic attacks
• Having any clinical condition, drug sensitivity, or prior therapy which, in the investigator's opinion, makes the participant unsuitable for the study
• Current use of antidepressants that may inhibit CYP2A6 or impact response to nicotine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fast Nicotine Metabolizers; Those in the upper tertile of NMR for cigarette/nicotine metabolism.	Other: cigarette; Participants will be allowed to smoke a cigarette prior to a PET scan and be abstinent from smoking prior to the other PET scan
Other: Slow Nicotine Metabolizers; Those in the lower tertile of NMR for cigarette/nicotine metabolism	Other: cigarette; Participants will be allowed to smoke a cigarette prior to a PET scan and be abstinent from smoking prior to the other PET scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occupancy of D2/3 receptors by [11C]-(+)-PHNO	Fast and slow nicotine metabolizers will have PET scans and occupancy of dopamine receptors will be measured using a PET scanner.	2 weeks

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Publications and helpful links

General Publications

• Di Ciano P, Tyndale RF, Mansouri E, Hendershot CS, Wilson AA, Lagzdins D, Houle S, Boileau I, Le Foll B. Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers. Int J Neuropsychopharmacol. 2018 Jun 1;21(6):503-512. doi: 10.1093/ijnp/pyx119.

Helpful Links

• Published data may be found at site above and PMID 29346545

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: July 31, 2015
• First Posted (Estimate): August 4, 2015

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: 111/2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided