Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 1

Conditions: Nicotine Dependence; Nicotine Vaping

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05962229

22-36348

1R01DA057282-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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18 participants in 3 patient groups

S-nicotine (tobacco) as the starting condition

Experimental group

Description:

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

Treatment:

Drug: Racemic nicotine

Drug: (R)- nicotine

Drug: (S)-Nicotine

R-nicotine (synthetic) as the starting condition

Experimental group

Description:

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

Treatment:

Drug: Racemic nicotine

Drug: (R)- nicotine

Drug: (S)-Nicotine

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

Experimental group

Description:

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.

Treatment:

Drug: Racemic nicotine

Drug: (R)- nicotine

Drug: (S)-Nicotine