Nicotine's Potential Abuse With Menthol

Impact of Menthol on the Abuse Potential of Nicotine

To examine if switching from menthol to non-menthol cigarettes will change the dose-effect curves for positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate in smokers.

Study Overview

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

Detailed Description

A placebo-controlled study that will recruit male and female menthol nicotine dependent smokers. Following screening and evaluation as described above, eligible participants will be enrolled in the study which will last about 4 weeks. Eligible, participants will be randomized to menthol or non-menthol smoking condition for 2 weeks (Phase 1) and then will be switched to the alternative condition for another 2 weeks (Phase 2). The smoking condition will be open label. Participants will be provided with free cigarettes in Phases 1 and 2. For the menthol condition, participants will be provided their usual brand of menthol cigarettes and for the non-menthol condition, they will be provided a matched-brand non-menthol cigarette (e.g., Newport Non-Menthol Gold 100s for those who smoke Newport Menthol Gold 100s). In week 2 of each Phase, participants will have a test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment. The period between the 2 Phases will not be longer than one week.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Stacy Minnix, B.S.; Phone Number: 4805 203-932-5711; Email: stacy.minnix@yale.edu

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Department of Veterans Affairs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year;
• 2) smoke ≥ 5 and less than 20 cigarettes per day;
• 3) urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker
• 4) not seeking treatment at the time of the study for nicotine dependence;
• 5) in good health as verified by medical history, screening examination, and screening laboratory tests;
• 6) for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion Criteria:

• 1) history of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study;
• 2) regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
• 3) current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine;
• 4) use of e-cigarettes more than 10 days in the past 30 days;
• 5) urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: menthol cigarettes; Will smoke only menthol cigarettes for two weeks	Drug: Nicotine; session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.; Other Names: intravenous nicotine
Active Comparator: non menthol cigarettess; Will only smoke non menthol cigarettes for two weeks	Drug: Nicotine; session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.; Other Names: intravenous nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
money choice questionaire	To explore the dose-effect curves of nicotine delivery rate for a) reinforcement (assessed with the Multiple-Choice Questionnaire), b) heart rate and blood pressure, and c) tobacco withdrawal severity, assessed with self-report symptoms and cognitive performance.	up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAFTEE	The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health (Levine & Schooler, 1986). It is a questionnaire that rates the current severity of a wide range of somatic, behavioral and affective symptoms in general and specific inquiry formats. It is designed to report adverse health events, regardless of whether or not they are suspected to be drug related, in order to reduce the under-reporting of unanticipated events compared with "known or expected" events.	up to one year

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D.,Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 31, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

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: 2000029223; 2U54DA036151-06 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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