Nicotine DependencePhase 1NCT05962229
Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine
A Phase 1 study testing (S)-Nicotine, (R)- nicotine and Racemic nicotine in people with Nicotine Dependence and Nicotine Vaping, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence, Nicotine Vaping
- What is being tested?
- (S)-Nicotine, (R)- nicotine and Racemic nicotine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2024to May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy on the basis of medical history and limited physical examination.
- Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)
Who cannot join
- • 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Zuckerberg San Francisco General Hospital (ZSFG)
San Francisco, California, 94110
Lisa Lawrence, 415-502-2465, lisa.lawrence@ucsf.edu
Armando Barraza, 415-502-2465, armando.barraza@ucsf.edu
About this study
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
- Being tested
- (S)-Nicotine, (R)- nicotine, Racemic nicotine
- Keywords
- Nicotine Pharmacokinetics, Nicotine Pharmacodynamics, Vaping, E-cigarettes
- Medical subject headings
- Tobacco Use Disorder, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
(S)-NicotineDrug
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)- nicotineDrug
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.
Racemic nicotineDrug
Also called 50:50 mixture of (S)- and (R)-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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: (S)-Nicotine; Drug: (R)- nicotine; Drug: Racemic nicotine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Nicotine Exposure Over Time
Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h)
Measured: Up to 7 hours
Secondary outcomes (1)
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
Measured: 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2023
- Study start6 Dec 2024
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Neal Benowitz, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05962229
- Sponsor's protocol ID
- 22-36348
- Other IDs
- 1R01DA057282-01
- Status last verified
- Dec 2025
- First submitted
- 17 Jul 2023
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine
- ClinicalTrials.gov ID
- NCT05962229
- Acronym / sponsor ID
- 22-36348
- Conditions
- Nicotine Dependence, Nicotine Vaping
- Keywords
- Nicotine Pharmacokinetics, Nicotine Pharmacodynamics, Vaping, E-cigarettes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 6 Dec 2024 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 27 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.
| Arm | Type | Receives |
|---|---|---|
| S-nicotine (tobacco) as the starting condition | Experimental | Drug: (S)-Nicotine, Drug: (R)- nicotine, Drug: Racemic nicotineParticipants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine. |
| R-nicotine (synthetic) as the starting condition | Experimental | Drug: (S)-Nicotine, Drug: (R)- nicotine, Drug: Racemic nicotineParticipants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine. |
| Racemic (50:50 S- and R- nicotine) as the starting condition | Experimental | Drug: (S)-Nicotine, Drug: (R)- nicotine, Drug: Racemic nicotineParticipants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy on the basis of medical history and limited physical examination.
- Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)
Key exclusion criteria (12 listed)
- • Medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| (S)-NicotineParticipants 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 (synthetic) as the starting condition, Racemic (50:50 S- and R- nicotine) as the starting condition, S-nicotine (tobacco) as the starting condition |
| (R)- nicotineParticipants 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 | 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 nicotineAlso: 50:50 mixture of (S)- and (R)-nicotineParticipants 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. | Drug | 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 |
Primary outcome
Mean Nicotine Exposure Over Time
Time frame: Up to 7 hours
Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h)
1 secondary outcome
Mean Amount of Nicotine Consumed Over Time
Time frame: 120 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Neal Benowitz, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing (S)-Nicotine, (R)- nicotine and Racemic nicotine in people with Nicotine Dependence and Nicotine Vaping, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lisa Lawrence (628-206-4204, lisa.lawrence@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Nicotine Exposure Over Time (time frame: Up to 7 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.