Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

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.

Study Overview

• Status: Recruiting
• Conditions: Nicotine Dependence; Nicotine Vaping
• Intervention / Treatment: Drug: (S)-Nicotine; Drug: (R)- nicotine; Drug: Racemic nicotine

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lisa Lawrence; Phone Number: 628-206-4204; Email: lisa.lawrence@ucsf.edu
• Study Contact Backup: Name: Armando Barraza; Phone Number: 510-560-4842; Email: armando.barraza@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Recruiting
      • Zuckerberg San Francisco General Hospital (ZSFG)
      • Principal Investigator: Neal Benowitz, MD
      • Contact: Lisa Lawrence; Phone Number: 415-502-2465; Email: lisa.lawrence@ucsf.edu
      • Contact: Armando Barraza; Phone Number: 415-502-2465; Email: armando.barraza@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-nicotine (tobacco) as the starting condition; Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.	Drug: (S)-Nicotine; 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.; Drug: (R)- nicotine; 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.; Drug: Racemic nicotine; 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.; Other Names: 50:50 mixture of (S)- and (R)-nicotine
Experimental: R-nicotine (synthetic) as the starting condition; Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.	Drug: (S)-Nicotine; 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.; Drug: (R)- nicotine; 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.; Drug: Racemic nicotine; 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.; Other Names: 50:50 mixture of (S)- and (R)-nicotine
Experimental: Racemic (50:50 S- and R- nicotine) as the starting condition; 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; 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.; Drug: (R)- nicotine; 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.; Drug: Racemic nicotine; 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.; Other Names: 50:50 mixture of (S)- and (R)-nicotine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Neal Benowitz, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: July 17, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Vaping; E-cigarettes; Nicotine Pharmacokinetics; Nicotine Pharmacodynamics
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Smoking; Tobacco Use Disorder; Vaping; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids; Solanaceous Alkaloids; Nicotine; nicotine 1-N-oxide
• Other Study ID Numbers: 22-36348; 1R01DA057282-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No