Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

Study Overview
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Brief Summary
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In a crossover study, experienced electronic cigarette users will vape 3 different forms of nicotine: natural (derived from tobacco), synthetic, or a 50:50 mixture of both natural and synthetic. The investigators will compare nicotine metabolism, cardiovascular effects, patterns of self-administration, and participants' feelings of craving/withdrawal and enjoyment.

Official Title
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Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

Conditions
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Nicotine Dependence, Nicotine Vaping

Intervention / Treatment
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* Drug: (S)-Nicotine
* Drug: (R)- nicotine
* Drug: Racemic nicotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy on the basis of medical history and limited physical examination. Current regular user of E-Cigarettes (≥ 15 days in the past 30 days) Exclusion Criteria: • Medications Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs). Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers). Concurrent use of nicotine-containing medications (Example: nicotine patch, lozenge, gum). Any stimulant medications (example: Adderall) generally given for ADHD treatment. • Pregnancy Pregnancy (self-reported and urine pregnancy test) Breastfeeding (determined by self-report) Women of childbearing potential must be using an acceptable method of contraception Inability to read and write in English A known propylene glycol/vegetable glycerin allergy Uncomfortable with getting blood drawn

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-nicotine (tobacco) as the starting condition<br>Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine. | Drug: (S)-Nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>Drug: (R)- nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>Drug: Racemic nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>* Other names: 50:50 mixture of (S)- and (R)-nicotine;|
| Experimental: R-nicotine (synthetic) as the starting condition<br>Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine. | Drug: (S)-Nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>Drug: (R)- nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>Drug: Racemic nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>* Other names: 50:50 mixture of (S)- and (R)-nicotine;|
| Experimental: Racemic (50:50 S- and R- nicotine) as the starting condition<br>Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine. | Drug: (S)-Nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>Drug: (R)- nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>Drug: Racemic nicotine<br>* Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.<br>* Other names: 50:50 mixture of (S)- and (R)-nicotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Nicotine Exposure Over Time | Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h) | Up to 7 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Amount of Nicotine Consumed Over Time | Nicotine self-administration determined by device weight change before and after use multiplied by the nicotine concentration in the e-liquid | 120 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine Pharmacokinetics, Nicotine Pharmacodynamics, Vaping, E-cigarettes