A study investigating the extraction of nicotine and flavors from tobacco free nicotine pods compared to tobacco based Swedish snus

INTERVENTION: The treatments are administered as single doses in a pre‐determined computer‐generated randomized order according to a four‐sequence list. Participants are randomly allocated as to what order they receive the following doses: 1. ZYN® Smooth containing 3 mg nicotine per portion ‐ 15 min single dose administration 2. ZYN® Smooth containing 3 mg nicotine per portion ‐ 60 min single dose administration 3. ZYN® Smooth containing 6 mg nicotine per portion ‐ 15 min single dose administration 4. ZYN® Smooth containing 6 mg nicotine per portion ‐ 60 min single dose administration 5. ZYN® Smooth containing 3 mg nicotine per portion (alternative manufacturing process) ‐ 15 min single dose administration 6. ZYN® Smooth containing 3 mg nicotine per portion (alternative manufacturing process) ‐ 60 min single dose administration 7. ZYN® Smooth containing 6 mg nicotine per portion (alternative manufacturing process) ‐ 15 min single dose administration 8. ZYN® Smooth containing 6 mg nicotine per portion (alternative manufacturing process) ‐ 60 min single dose administration 9. ZYN® Wintergreen containing 3 mg nicotine per portion (Nicotine analysis) ‐ 60 min single dose administration 10. ZYN® Wintergreen containing 3 mg nicotine per portion (Flavor analysis) ‐ 60 min single dose administration 11. ZYN® Peppermint containing 3 mg nicotine per portion (Nicotine and Flavor analysis) ‐ single dose 60 min administration 12. ZYN® Spearmint containing 3 mg nicotine per portion (Nicotine and Flavor analysis) ‐ 60 min single dose administration 13. Swedish portion snus PSWL 1.0 g (8 mg nicotine/g) ‐ 15 min single dose administration 14. Swedish portion snus PSWL 1.0 g (8 mg nicotine/g) ‐ 60 min single dose administration The treatments are administered as single doses in a pre‐determined randomised order. The participant keeps the pouch still between the upper lip and the gum for 15 or 60 minutes. The total duration of the treatments and follow‐up for all study arms CONDITION: Tobacco use not otherwise specified (NOS) ; Not Applicable ; Tobacco use PRIMARY OUTCOME: Extracted dose of nicotine from each portion is measured by using GC‐MS analysis and calculated by subtracting the residual amount after use from the mean of 10 unused portions. Used portions are freezed after dosing and analysis using GC‐MS is performed at the end of the trial. SECONDARY OUTCOME: 1. Pulse rate is measured using a pulsimeter at baseline, five, ten, 15, 30 and 60 minutes; 2. Head buzz (head rush, “hit”, feeling alert, overall “product strength” is measured using a 100‐mm visual analogue scale (VAS) at preset time points up to 30 and 60 minutes, respectively, after study product administration (as a proxy for systemic uptake); 3. The extracted dose of flavor components are measured using GC‐MS analysis and calculated by subtracting the residual amount after use from the mean of 10 unused portions. Used portions are freezed after dosing and analysis using GC‐MS is performed at the end of the trial.; 4. Adverse events are measured using patient interviews at predose, five, ten, 15, 30 and 60 minutes INCLUSION CRITERIA: 1. Snus user, with a minimum weekly consumption of three or more snus cans (brands with nicotine content <1%) or two or more cans (brands with nicotine content >1%) since =1 year 2. Consent to participate voluntarily and sign Informed Consent Form prior to any study procedure 3. Healthy male/female, age =19. Female subjects should have a negative pregnancy test. 4. Willing and able to comply with study procedures 5. A heart rate increase = 10 beats/min with first use of snus in the morning after overnight abstinence from any nicotine exposure