Nicotine Addiction
Conditions
Keywords
Nicotine, smokers, vitals associated with smoking
Brief summary
The proposed study will examine the threshold for nicotine self-administration (NSA) using five different nicotine doses in young adult male and female non-dependent smokers (light and intermittent smokers or LITS). We propose a double-blind, placebo-controlled study that will enroll 195 individuals, targeting a total of 72 completers (36 male and 36 females). In each of the five experimental sessions, smokers will be randomly assigned to one of the five doses of nicotine (0.0125, 0.025, 0.05, 0.1 and 0.2 mg/70 kg). The highest dose, 0.2 mg/70 kg, corresponds to nicotine delivered by about one or two puffs of a cigarette. At the beginning of each experimental session, smokers will sample the assigned both the nicotine dose for that experimental session, and the placebo (saline) dose, followed by the opportunity to choose between nicotine and placebo for a total of ten choices over a 150-minute period. The main outcomes will be threshold dose (the minimum dose of nicotine that is self-administered more than placebo) and the slope of dose-response for nicotine self-administration (changes in nicotine self-administration per unit change in nicotine dose). We will also collect measures of nicotine intake (cotinine), nicotine clearance (3-hydroxycotinine (3-HC) / cotinine), and self-report drug effects
Detailed description
Aim #1: To assess the threshold reinforcing dose and dose-effect curve for IV NSA at low doses in young adult LITS. Hypothesis #1A: The threshold reinforcing doses for IV NSA will be between 0.0125 to 0.1 mg/70 kg. Hypothesis #1B: The dose-effect curve for NSA will differ between males and females with relatively flat curve in female smokers. Aim #2: To assess the threshold and dose-effect curve for the positive and negative/aversive subjective effects of IV nicotine at low doses and its relationship to nicotine reinforcement. Hypothesis #2 A: The threshold for the positive effects will be between 0.0125 to 0.1 mg/70 kg, for the negative/aversive effect it will be ≥ 0.1 mg/70 kg. Hypothesis #2B: Nicotine reinforcement will be positively correlated with the positive and negatively correlated with the negative/aversive subjective effects of IV nicotine. Exploratory Aims: To examine the influence of nicotine clearance rate on nicotine reinforcement threshold and dose-effect curve.
Interventions
DRUGSaline
5cc's of saline give at least once.
DRUGNicotine
(0.0125, 0.025, 0.0.5, 0.1 and 0.2 mg/70 kg or about 0.18, 0.36, 0.7, 1.4 and 2.8 µg/kg).
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
1) Female and male smokers, aged 18 to30 years, who have been smoking for at least a year, and a life-time consumption of at least 100 cigarettes; 2) smoke more frequently than once a week and ≤5 cpd; 3) FTND score \<3 indicating no or minimal evidence for nicotine dependence; 4) urine cotinine levels \>100 ng/mL indicating smoking status and a level \<1000 mg/mL consistent with nicotine intake of LITS; 5) not seeking treatment at the time of the study for nicotine dependence; 6) in good health as verified by medical history, screening examination, and screening laboratory tests; 7) 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 illnesses that the physician investigator deems as contraindicated for the subject to be in the study; 2) requirement of any form of regular psychotropic medication (antidepressants, antipsychotics, or anxiolytics) or psychiatric diagnosis and treatment for psychiatric disorders including major depression, bipolar disorder, schizophrenia in the past 6 months; and 3) current dependence to alcohol or any other recreational or prescription drugs and; 4) daily use of smokeless tobacco products or exclusive daily use of e-cigarettes (non-daily users will be included).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DEQ - Pleasurable | Up to 10 Minutes | The Drug Effects Questionnaire (DEQ) ratings subscale that measures the pleasurable effects was used. I The minimum score is zero with the maximum score of a 100millimeters. The higher the score means the more pleasurable. |
| DEQ - Aversive | Up to 10 Minutes | The DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. rug Effects Questionnaire (DEQ) ratings subscale that measures the aversive effects was used. The higher the score means more aversive. |
| DEQ - Stimulatory | Up to10 Minutes | The Drug Effects Questionnaire (DEQ) ratings subscale that measures the stimulatory effects was used. DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. The higher the score means more stimulation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Participants In this crossover study, all participants received all 5 treatments, including placebo. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Study Participants |
|---|---|
| Age, Continuous | 26.7 years STANDARD_DEVIATION 3.1 |
| Average cigarettes per day | 4.5 cigarettes per day STANDARD_DEVIATION 1.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| FTND | 1.6 units on a scale STANDARD_DEVIATION 1.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 34 participants |
| Serum cotinine level | 137.4 ng/mL STANDARD_DEVIATION 104 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 23 Participants |
| Years of smoking | 8.7 years STANDARD_DEVIATION 4.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 31 | 0 / 32 | 0 / 33 | 0 / 31 | 0 / 33 |
| other Total, other adverse events | 0 / 34 | 0 / 31 | 0 / 32 | 0 / 33 | 0 / 31 | 0 / 33 |
| serious Total, serious adverse events | 0 / 34 | 0 / 31 | 0 / 32 | 0 / 33 | 0 / 31 | 0 / 33 |
Outcome results
Primary
DEQ - Aversive
The DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. rug Effects Questionnaire (DEQ) ratings subscale that measures the aversive effects was used. The higher the score means more aversive.
Time frame: Up to 10 Minutes
Population: Thirty four subject were randomized, 4 didn't complete all five test sessions, the sessions that were completed were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | DEQ - Aversive | Placebo | 1.30 score on a scale | Standard Error 0.2 |
| Study Participants | DEQ - Aversive | 0.0125 | 1.26 score on a scale | Standard Error 0.22 |
| Study Participants | DEQ - Aversive | 0.025 | 1.50 score on a scale | Standard Error 0.22 |
| Study Participants | DEQ - Aversive | 0.05 | 1.21 score on a scale | Standard Error 0.22 |
| Study Participants | DEQ - Aversive | 0.1 | 1.22 score on a scale | Standard Error 0.22 |
| Study Participants | DEQ - Aversive | 0.2 | 1.37 score on a scale | Standard Error 0.22 |
Primary
DEQ - Pleasurable
The Drug Effects Questionnaire (DEQ) ratings subscale that measures the pleasurable effects was used. I The minimum score is zero with the maximum score of a 100millimeters. The higher the score means the more pleasurable.
Time frame: Up to 10 Minutes
Population: Thirty four subject were randomized, 4 didn't complete all five test sessions, the sessions that were completed were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | DEQ - Pleasurable | Placebo | 2.14 score on a scale | Standard Error 0.2 |
| Study Participants | DEQ - Pleasurable | 0.0125 | 2.05 score on a scale | Standard Error 0.26 |
| Study Participants | DEQ - Pleasurable | 0.025 | 1.98 score on a scale | Standard Error 0.26 |
| Study Participants | DEQ - Pleasurable | 0.05 | 2.37 score on a scale | Standard Error 0.25 |
| Study Participants | DEQ - Pleasurable | 0.1 | 2.67 score on a scale | Standard Error 0.26 |
| Study Participants | DEQ - Pleasurable | 0.2 | 3.24 score on a scale | Standard Error 0.26 |
Primary
DEQ - Stimulatory
The Drug Effects Questionnaire (DEQ) ratings subscale that measures the stimulatory effects was used. DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. The higher the score means more stimulation.
Time frame: Up to10 Minutes
Population: Thirty four subject were randomized, 4 didn't complete all five test sessions, the sessions that were completed were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | DEQ - Stimulatory | Placebo | 1.95 score on a scale | Standard Error 0.2 |
| Study Participants | DEQ - Stimulatory | 0.0125 | 1.82 score on a scale | Standard Error 0.25 |
| Study Participants | DEQ - Stimulatory | 0.025 | 1.85 score on a scale | Standard Error 0.25 |
| Study Participants | DEQ - Stimulatory | 0.05 | 2.29 score on a scale | Standard Error 0.24 |
| Study Participants | DEQ - Stimulatory | 0.1 | 2.76 score on a scale | Standard Error 0.25 |
| Study Participants | DEQ - Stimulatory | 0.2 | 3.18 score on a scale | Standard Error 0.24 |