Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

NCT05962229 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 22-363481R01DA057282-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nicotine Dependence; Nicotine Vaping

Keywords

Nicotine Pharmacokinetics; Nicotine Pharmacodynamics; Vaping; E-cigarettes

Outcome Measures

Primary Outcomes (1)

• Mean Nicotine Exposure Over Time

  Plasma nicotine area under the concentrated time curve (AUC) (ng/ml\*h)

  Up to 7 hours

Secondary Outcomes (1)

• Mean Amount of Nicotine Consumed Over Time

  120 minutes

Study Arms (3)

S-nicotine (tobacco) as the starting condition

EXPERIMENTAL

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.

Drug: (S)-Nicotine; Drug: (R)- nicotine; Drug: Racemic nicotine

R-nicotine (synthetic) as the starting condition

EXPERIMENTAL

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.

Drug: (S)-Nicotine; Drug: (R)- nicotine; Drug: Racemic nicotine

Racemic (50:50 S- and R- nicotine) as the starting condition

EXPERIMENTAL

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; Drug: (R)- nicotine; Drug: Racemic nicotine

Interventions

(S)-Nicotine DRUG

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.

R-nicotine (synthetic) as the starting condition; Racemic (50:50 S- and R- nicotine) as the starting condition; S-nicotine (tobacco) as the starting condition

(R)- nicotine DRUG

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.

R-nicotine (synthetic) as the starting condition; Racemic (50:50 S- and R- nicotine) as the starting condition; S-nicotine (tobacco) as the starting condition

Racemic nicotine DRUG

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.

Also known as: 50:50 mixture of (S)- and (R)-nicotine

R-nicotine (synthetic) as the starting condition; Racemic (50:50 S- and R- nicotine) as the starting condition; S-nicotine (tobacco) as the starting condition

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy on the basis of medical history and limited physical examination.
• Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Zuckerberg San Francisco General Hospital (ZSFG)

San Francisco, California, 94110, United States

RECRUITING

MeSH Terms

Conditions

Tobacco Use Disorder; Vaping

Interventions

Nicotine; nicotine 1-N-oxide

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Neal Benowitz, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Lawrence

CONTACT

628-206-4204; lisa.lawrence@ucsf.edu

Armando Barraza

CONTACT

510-560-4842; armando.barraza@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.

Study Record Dates

• First Submitted: July 17, 2023
• First Posted: July 27, 2023
• Study Start: December 6, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)