Effects of Menthol in E-cigarettes on Smoking Behaviors

The overall goal of this proposal is to understand the relationship between nicotine metabolism and menthol flavor in e-cigarettes on smoking behavior in smokers.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Nicotine

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Connecticut Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• At least 21 years of age
• Able to read and write English.
• Smoking at least 1 menthol cigarettes/cigars/little cigars per day
• Report regular menthol cigarette use
• Have at least 200ng/ml urine cotinine
• Willing to abstain from combustible tobacco products 12 hrs prior to each experimental session.
• not planning a smoking quit attempt.
• Have not stopped use due to COVID.
• used e-cigarettes at least 10 times in the past six months.
• Fully vaccinated against COVID-19.
• must report history of JUUL and other nicotine salt/pod devices (i.e., JUUL-like)

Exclusion Criteria:

• Use of psychoactive drugs including anxiolytics, antidepressants, and other psychostimulants unless prescribed and stable for two months.
• Current diagnosis of any severe psychiatric disorder
• Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, pulmonary or hepatic pathology that would increase risk or would interfere with/mimic tobacco abstinence.
• Known hypersensitivity to propylene glycol and nut allergies.
• Pregnant or lactating females.
• current criteria for moderate or severe cannabis and alcohol use disorder per DSM-5 criteria.
• current criteria for other substance use disorders per DSM-5 criteria.
• Seeking treatment to stop smoking.
• individuals who do not want to use e-cigarettes.
• Uncontrolled asthma (defined as <20 on Asthma Control Test) AND/OR endorsement of "yes" to environmentally induced bronchospasm that requires prescription Epipen)
• blood pressure >170/>100 and heart rate >100
• vaping of CBD/THC or marijuana related products in the past 3 months
• For current THC vapers: Any report of mild or great EVALI-related symptoms (i.e. cough, shortness of breath, chest pain, nausea, vomiting, stomach pain, diarrhea, fever, chills, or weight loss) without non-EVALI reasonable and proximal cause

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5% nicotine with menthol flavor and tobacco flavor; All participants will receive 5% nicotine/menthol and 5% nicotine/tobacco e-cigarettes over the course of 2 lab sessions; the order of which flavor goes first at each lab session is counterbalanced with half getting menthol flavor first and half getting tobacco flavor first.	Drug: Nicotine; Participants will receive 5% nicotine in two flavor exposures via e-cigarettes. Each exposure will be 10 3-sec puffs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Nicotine Levels	Mean plasma levels obtained after e-cigarette administration at each lab session (lab 1 and lab 2).	Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.
Nicotine Metabolic Rate	Mean Area under the curve (AUC) for plasma nicotine and NMR were computed and then log transformed to reduce skewness of the two measures.	Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
e-cigarette craving	Labeled Magnitude Scale ; -100 (no sensation) to 100 (strongest imaginable)	up to 3 weeks
irritation/harshness	Labeled Magnitude Scale ; -100 (no sensation) to 100 (strongest imaginable)	up to 3 weeks
liking of e-cigarette	Labeled Hedonic Scale ; -100 (most disliked) to 100 (most liked)	up to 3 weeks
coolness	Labeled Magnitude Scale ; -100 (no sensation) to 100 (strongest imaginable)	up to 3 weeks
nicotine withdrawal	Drug effect questionnaire; 0("not at all") to 100("extremely") mm scale	up to 3 weeks
stimulation	Drug effect questionnaire: 0("not at all") to 100("extremely") mm scale	up to 3 weeks
liking of e-cigarette	Drug effect questionnaire: 0("not at all") to 100("extremely") mm scale	up to 3 weeks
e-cigarette use	time line follow back	up to 2 weeks
cigarette use	timeline follow back	up to 2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rate	beats per minute	up to 5 weeks
blood pressure	diastolic and systolic measurements	up to 5 weeks
pulse oximetry	measurement of oxygen in blood	up to 5 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: August 1, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids; Solanaceous Alkaloids; Nicotine
• Other Study ID Numbers: 2000028570; 2U54DA036151-06 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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