Nicotine's Potential Abuse With Menthol

Early Phase 1

Completed

Conditions: Nicotine Dependence

Interventions: Drug: Nicotine

Registration Number: NCT04535362

Lead Sponsor: Yale University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

Inclusion Criteria

1. Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year;
1. smoke ≥ 5 and less than 20 cigarettes per day;
1. urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker
1. not seeking treatment at the time of the study for nicotine dependence;
1. in good health as verified by medical history, screening examination, and screening laboratory tests;
1. 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;
1. regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
1. current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine;
1. use of e-cigarettes more than 10 days in the past 30 days;
1. urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
non menthol cigarettess	Nicotine	Will only smoke non menthol cigarettes for two weeks
menthol cigarettes	Nicotine	Will smoke only menthol cigarettes for two weeks

Primary Outcome Measures

Name	Time	Method
Drug Effect Questionnaire - Pleasure Effect	Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes	Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Drug Effect Questionnaire - Aversive Effect	Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes	Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Drug Effect Questionnaire - Head Rush	Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes	Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on all subscales, including Head Rush scale, range from 0 - 100 where lower scores indicate less head rush.
Drug Effect Questionnaire - Stimulatory Effects	Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes	Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.

Secondary Outcome Measures

Name	Time	Method
SAFTEE	up to one year	The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health. 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.