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): 10
• 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: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: menthol flavor; Participants will receive 5% nicotine in an e-cigarette	Drug: Nicotine; Participants will receive two nicotine concentrations via e-cigarettes. Each exposure will be 10 3-sec puffs and ad libitum use
Experimental: tobacco flavor; Participants will receive 5% nicotine in an e-cigarette	Drug: Nicotine; Participants will receive two nicotine concentrations via e-cigarettes. Each exposure will be 10 3-sec puffs and ad libitum use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma nicotine levels	blood samples obtained at baseline and 2, 5, 15, 30, 45, 60, 90, 120, and 180 minutes after nicotine exposure	up to 3 weeks
Nicotine Metabolic Rate	blood samples obtained at baseline and 2, 5, 15, 30, 45, 60, 90, 120, and 180 minutes after nicotine exposure	up to 3 weeks

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 (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; 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