Nicotine Dependence, Tobacco Smoking
Conditions
Brief summary
Socioemotional processing dysfunctions (i.e., disruptions in affective, cognitive, and neural processes that encode, interpret, and respond to socially and emotionally relevant stimuli) have been implicated in tobacco smoking and relapse, however this potential target for medication development has not been systematically examined. Evidence from animal and human laboratories indicate that administration of intranasal oxytocin enhances socioemotional processing and may be efficacious for the treatment of drug addiction, including nicotine dependence. In order to evaluate the potential efficacy of intranasal oxytocin for smoking cessation, this laboratory-based proposal will examine whether intranasal oxytocin attenuates smoking lapse, nicotine withdrawal, and socioemotional processing disruptions in regular smokers following overnight abstinence.
Interventions
DRUGOxytocin
DRUGPlacebo
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 18-40 * Smoke \>= 10 cig/day for the past year * English fluency
Exclusion criteria
* Current DSM-5 substance use disorder, excluding nicotine dependence (to minimize alcohol or drug withdrawal symptoms during the study sessions) * Any medical condition that would increase risk for study participation (such as sinus infection or other condition blocking access to the olfactory epithelium) * Women who are pregnant or nursing * Current use of psychiatric medication * Breath Carbon Monoxide (CO) levels \< 10ppm measured during study intake (to exclude individuals who overreport smoking in order to participate in the study) * Planning to quit or reduce smoking in the next 30 days * Current regular use of other nicotine products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Lapse Analogue Task (Delay Score) | 2.5 hours after nasal spray administration | This task measures ability to resist the temptation to initiate smoking under conditions in which it is advantageous to remain abstinent. The delay score is the number of minutes before participants begin smoking (minimum = 0 minutes to maximum = 50 minutes). A higher number is better. |
| Brief Questionnaire of Smoking Urges (QSU) | 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray | The Brief Questionnaire of Smoking Urges (QSU) is a 10-item self-report questionnaire measures desire, intention, urge, and need to smoke. The QSU was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Scores at each assessment time are calculated as the mean of all 10 items (minimum = 0 to maximum = 5). Each session's scores are then calculated as the mean scores of post-spray assessments. A lower score is better. |
| Systolic Blood Pressure (mmHg) | 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray | Systolic blood pressure (SP) was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's values are calculated as the mean of post-spray assessments. |
| Diastolic Blood Pressure (mmHg) | 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray | Diastolic blood pressure (DP) was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's values are calculated as the mean of post-spray assessments. |
| Heart Rate (Bpm) | 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray | Heart rate (HR) was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's values are calculated as the mean of post-spray assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Profile of Mood States (Anxious Scale) | 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray | The Profile of Mood States (POMS) lists 72 affective adjectives that are rated on 0 to 4-point. The main measure for this study is the Anxious scale, calculated as the mean of 6 anxiety-related items. The POMS was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's scores are calculated as the mean scores of post-spray assessments. Lower scores are better. |
Countries
United States
Participant flow
Pre-assignment details
No participants were excluded pre-assignment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then Intranasal Oxytocin (40 IU) Participants received a single placebo nasal spray (consisting of 4ml sterile saline \[Ocean Nasal Spray Solution\]) during the first experimental session, which occurred on a single day. After a 72 hour washout period, they then received a single 40 IU dose of Pitocin (oxytocin, USP; concentration = 10 IU/1 mL; PAR Pharmaceuticals, NY, USA) during the second experimental session, which occurred on a single day. All nasal spray solutions were transferred into two, 2 ml intranasal atomizers and administered in four sprays to each nostril over the course of 10 minutes. | 45 |
| Intranasal Oxytocin (40 IU) Then Placebo Participants received a single 40 IU dose of Pitocin (oxytocin, USP; concentration = 10 IU/1 mL; PAR Pharmaceuticals, NY, USA) during the first experimental session, which occurred on a single day. After a 72 hour washout period, they then received a single placebo nasal spray (consisting of 4ml sterile saline \[Ocean Nasal Spray Solution\]) during the second experimental session, which occurred on a single day. All nasal spray solutions were transferred into two, 2 ml intranasal atomizers and administered in four sprays to each nostril over the course of 10 minutes. | 38 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 12 | 7 |
Baseline characteristics
| Characteristic | Placebo Then Intranasal Oxytocin (40 IU) | Total | Intranasal Oxytocin (40 IU) Then Placebo |
|---|---|---|---|
| Age, Continuous | 30.8 years STANDARD_DEVIATION 5.4 | 30.3 years STANDARD_DEVIATION 5.4 | 29.8 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 13 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 70 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 37 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) White | 13 Participants | 22 Participants | 9 Participants |
| Region of Enrollment United States | 45 participants | 83 participants | 38 participants |
| Sex: Female, Male Female | 19 Participants | 31 Participants | 12 Participants |
| Sex: Female, Male Male | 26 Participants | 52 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 64 |
| other Total, other adverse events | 0 / 64 | 0 / 64 |
| serious Total, serious adverse events | 0 / 64 | 0 / 64 |
Outcome results
Primary
Brief Questionnaire of Smoking Urges (QSU)
The Brief Questionnaire of Smoking Urges (QSU) is a 10-item self-report questionnaire measures desire, intention, urge, and need to smoke. The QSU was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Scores at each assessment time are calculated as the mean of all 10 items (minimum = 0 to maximum = 5). Each session's scores are then calculated as the mean scores of post-spray assessments. A lower score is better.
Time frame: 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Oxytocin (40 IU) | Brief Questionnaire of Smoking Urges (QSU) | 2.46 score on a scale | Standard Error 0.12 |
| Placebo | Brief Questionnaire of Smoking Urges (QSU) | 2.49 score on a scale | Standard Error 0.11 |
Primary
Diastolic Blood Pressure (mmHg)
Diastolic blood pressure (DP) was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's values are calculated as the mean of post-spray assessments.
Time frame: 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Oxytocin (40 IU) | Diastolic Blood Pressure (mmHg) | 77.5 mmHg | Standard Error 1.1 |
| Placebo | Diastolic Blood Pressure (mmHg) | 74.7 mmHg | Standard Error 1.1 |
Primary
Heart Rate (Bpm)
Heart rate (HR) was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's values are calculated as the mean of post-spray assessments.
Time frame: 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Oxytocin (40 IU) | Heart Rate (Bpm) | 65.6 bpm | Standard Error 0.7 |
| Placebo | Heart Rate (Bpm) | 65.9 bpm | Standard Error 0.7 |
Primary
Smoking Lapse Analogue Task (Delay Score)
This task measures ability to resist the temptation to initiate smoking under conditions in which it is advantageous to remain abstinent. The delay score is the number of minutes before participants begin smoking (minimum = 0 minutes to maximum = 50 minutes). A higher number is better.
Time frame: 2.5 hours after nasal spray administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Oxytocin (40 IU) | Smoking Lapse Analogue Task (Delay Score) | 11.5 minutes | Standard Error 2.3 |
| Placebo | Smoking Lapse Analogue Task (Delay Score) | 10.9 minutes | Standard Error 2.3 |
Primary
Systolic Blood Pressure (mmHg)
Systolic blood pressure (SP) was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's values are calculated as the mean of post-spray assessments.
Time frame: 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Oxytocin (40 IU) | Systolic Blood Pressure (mmHg) | 122.1 mmHg | Standard Error 1.4 |
| Placebo | Systolic Blood Pressure (mmHg) | 118.2 mmHg | Standard Error 1.4 |
Secondary
Profile of Mood States (Anxious Scale)
The Profile of Mood States (POMS) lists 72 affective adjectives that are rated on 0 to 4-point. The main measure for this study is the Anxious scale, calculated as the mean of 6 anxiety-related items. The POMS was assessed 30 minutes before the nasal spray, and again 30, 60, and 90 minutes after the nasal spray during each session. Each session's scores are calculated as the mean scores of post-spray assessments. Lower scores are better.
Time frame: 30 minutes before nasal spray, and 30, 60, and 90 minutes after nasal spray
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Oxytocin (40 IU) | Profile of Mood States (Anxious Scale) | 0.82 score on a scale | Standard Error 0.04 |
| Placebo | Profile of Mood States (Anxious Scale) | 0.71 score on a scale | Standard Error 0.04 |