Anxiety, Depression, Stress
Conditions
Keywords
Aromatherapy, Smell
Brief summary
The purpose of this study is to examine the body's response to relaxing and stimulating fragrances commonly used in aromatherapy.
Detailed description
Despite aromatherapy's popularity, efficacy data are scant, and potential mechanisms are controversial. This randomized controlled trial examined the psychological, autonomic, endocrine, and immune consequences of one purported relaxant odor (lavender), one stimulant odor (lemon), and a no-odor control (water), before and after a stressor (cold pressor); 56 healthy men and women were exposed to each of the odors during three separate visits. To assess the effects of expectancies, participants randomized to the blind condition were given no information about the odors they would smell; primed individuals were told what odors they would smell during the session, and what changes to expect. Experimenters were blind. In each case we measured several different aspects of the cellular immune response, as well as skin barrier repair following tape stripping. This design allowed us to examine the ability of the odors to modulate endocrine and immune function, and health-relevant cutaneous responses.
Interventions
BEHAVIORALExposure to relaxant and stimulant odors
A yellow-tinted cotton ball containing 100 ml of the essential oil or distilled water was taped between the nose and upper lip on top of a piece of surgical tape; use of the barrier tape avoided percutaneous absorption . This method provided continuous and uniform exposure across subjects that would not have been possible with ambient room inhalation, and helped maintain experimenter blindness.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 44 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults with a normal sense of smell
Exclusion criteria
* Treatment with medication that has immunological or endocrinological consequences * Chronic health problems that affect immune or endocrine systems * Allergy to perfume or cosmetics * Problems with sense of smell * Respiratory problems * Smoker * Current active asthma * Use of psychoactive drugs or mood-altering medication * History of anxiety disorder, major depression, bipolar disorder, schizophrenia, or other psychotic disorders * History of chest pain or ventricular fibrillation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortisol and Catecholamine Production | 3 Visits with at least 2 weeks between each. Average time to complete all visits was 64.46 days (SD 48.4). Cortisol: 9:05, 10:05, 10:55, 11:45, 12:15, 13:00. Nor/Epi: 9:05, 10:05, 10:55, 11:05, 11:45, 12:15 | Cortisol, norepinephrine, epinephrine measured before and after physical (cold pressor) stressor, which occurred at 11:00. |
| Immune Function | 3 Visits with at least 2 weeks between each. Average time to complete all visits was 64.46 days (SD 48.4). 9:05, 10:05, 11:45 | Stimulated Cytokine Production (Interleukin-6 (IL-6), Interleukin-10 (IL-10)) measured before and after cold pressor stressor, which occurred at 11:00. |
| Skin Barrier Repair | 3 Visits with at least 2 weeks between each. Average time to complete all visits was 64.46 days (SD 48.4).10:05, 11:45, 13:15 | TEWL (Transepidermal Water Loss, via tape stripping procedure)measured before and after cold pressor stressor (11:00). After obtaining baseline measurements on volar forearm, cellophane tape(3M Scotch-type; St. Paul, MN) was applied repeatedly (6-50 times) to remove superficial layer of cornified skin cells. Tape stripping stopped when TEWL was elevated from the basal level of 5-7 g/h/m2 to at least 20 g/h/m2. The number of strips required to reach TEWL X20 g/m2/h was the measure of barrier. TEWL was measured with a computerized evaporimetry instrument, the DermaLabs (CyberDERM, Media, PA). |
| Immune Function: Delayed Hypersensitivity to Candida(DTH) | Day 1 11:45, Day 2 (24h) 11:45, Day 3 (48h) 11:45, Day 4 (72h) 11:45. | DTH memory responses to a common infectious agent provided a measure of T-cell immunity. Nurses inoculated subject's arm with 0.1ml Candida (stock solution diluted 1:20 in saline, Greer Labs, NC) intradermally, after the cold pressor stressor. The wheal diameter (2 dimensions) was self-assessed at 24, 48, and 72 hours by participants given detailed instructions and templates for measurement. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through ads posted in the Columbus, Ohio area.
Pre-assignment details
We excluded individuals taking cardiovascular medications or medications with obvious immunological or endocrinological consequences. Additional exclusion criteria included perfume allergies, smoking, problems with smell/taste, respiratory problems, asthma, excessive alcohol/caffeine use.
Participants by arm
| Arm | Count |
|---|---|
| Lavender Oil / Lemon Oil / Water Control A yellow-tinted cotton ball containing 100 μL of the essential oil or water placebo was taped between the nose and upper lip. Within-subject design was used; each subject was exposed to each of the three odors (lemon, lavender, no odor). | 56 |
| Total | 56 |
Baseline characteristics
| Characteristic | Lavender Oil / Lemon Oil / Water Control |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 56 Participants |
| Age Continuous | 24.41 years STANDARD_DEVIATION 6.05 |
| Region of Enrollment United States | 56 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 56 |
| serious Total, serious adverse events | 0 / 56 |
Outcome results
Primary
Cortisol and Catecholamine Production
Cortisol, norepinephrine, epinephrine measured before and after physical (cold pressor) stressor, which occurred at 11:00.
Time frame: 3 Visits with at least 2 weeks between each. Average time to complete all visits was 64.46 days (SD 48.4). Cortisol: 9:05, 10:05, 10:55, 11:45, 12:15, 13:00. Nor/Epi: 9:05, 10:05, 10:55, 11:05, 11:45, 12:15
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lavender | Cortisol and Catecholamine Production | Epinephrine (post stress) | 43.5 pg/ml (log 10) | Standard Deviation 32.7 |
| Lavender | Cortisol and Catecholamine Production | Cortisol (post stress) | 0.107 pg/ml (log 10) | Standard Deviation 0.056 |
| Lavender | Cortisol and Catecholamine Production | Norepinephrine (Change pre to post stress) | 0.03 pg/ml (log 10) | Standard Deviation 0.02 |
| Water Control | Cortisol and Catecholamine Production | Epinephrine (post stress) | 44.3 pg/ml (log 10) | Standard Deviation 24.2 |
| Water Control | Cortisol and Catecholamine Production | Cortisol (post stress) | 0.119 pg/ml (log 10) | Standard Deviation 0.071 |
| Water Control | Cortisol and Catecholamine Production | Norepinephrine (Change pre to post stress) | 0.03 pg/ml (log 10) | Standard Deviation 0.01 |
| Lemon | Cortisol and Catecholamine Production | Cortisol (post stress) | 0.107 pg/ml (log 10) | Standard Deviation 0.056 |
| Lemon | Cortisol and Catecholamine Production | Norepinephrine (Change pre to post stress) | 0.073 pg/ml (log 10) | Standard Deviation 0.024 |
| Lemon | Cortisol and Catecholamine Production | Epinephrine (post stress) | 38.3 pg/ml (log 10) | Standard Deviation 17.9 |
Comparison: Cortisol. Analyses consisted of repeated-measures linear models fit to each dependent variable.IVs assessed in each model were odor, time, gender, expectancy group (primed vs. blind), their interactions;baseline level of the DV was included as a covariate. Post hoc tests were used as appropriate. A two-sided significance level of alpha = 0.05 was used. Model controlled for Time 1 baseline.p-value: 0.83Regression, Linear
Comparison: Epinephrine. Analyses consisted of repeated-measures linear models fit to each dependent variable.IVs assessed in each model were odor, time, gender, expectancy group (primed vs. blind), their interactions;baseline level of the DV was included as a covariate. Post hoc tests were used as appropriate. A two-sided significance level of alpha = 0.05 was used. Model controlled for Time 1 baseline.p-value: 0.16Mixed Models Analysis
Comparison: Norepinephrine. Model controlled for Time 1 baseline. Comparing timepoints 4 and 5 for pre versus post stressor, e.g. lemon versus water control; Citrus(5-4)-Water(5-4).p-value: 0.017Mixed Models Analysis
Primary
Immune Function
Stimulated Cytokine Production (Interleukin-6 (IL-6), Interleukin-10 (IL-10)) measured before and after cold pressor stressor, which occurred at 11:00.
Time frame: 3 Visits with at least 2 weeks between each. Average time to complete all visits was 64.46 days (SD 48.4). 9:05, 10:05, 11:45
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lavender | Immune Function | IL-6 | 3.706 pg/ml | Standard Deviation 0.814 |
| Lavender | Immune Function | IL-10 | 1.777 pg/ml | Standard Deviation 0.48 |
| Water Control | Immune Function | IL-6 | 3.622 pg/ml | Standard Deviation 0.857 |
| Water Control | Immune Function | IL-10 | 1.734 pg/ml | Standard Deviation 0.463 |
| Lemon | Immune Function | IL-6 | 3.623 pg/ml | Standard Deviation 0.904 |
| Lemon | Immune Function | IL-10 | 1.787 pg/ml | Standard Deviation 0.458 |
Comparison: IL-6. Mixed effect linear models were used to test the hypothesis. These models included the post-odor and post-stress dependent variable measurements with a covariate for the baseline pre-odor measurement. Base 10 logarithms were used for each dependent variable and baseline covariate.p-value: 0.1Mixed Models Analysis
Comparison: IL-10. Mixed effect linear models were used to test the hypothesis. These models included the post-odor and post-stress dependent variable measurements with a covariate for the baseline pre-odor measurement. Base 10 logarithms were used for each dependent variable and baseline covariate.p-value: 0.5Mixed Models Analysis
Primary
Immune Function: Delayed Hypersensitivity to Candida(DTH)
DTH memory responses to a common infectious agent provided a measure of T-cell immunity. Nurses inoculated subject's arm with 0.1ml Candida (stock solution diluted 1:20 in saline, Greer Labs, NC) intradermally, after the cold pressor stressor. The wheal diameter (2 dimensions) was self-assessed at 24, 48, and 72 hours by participants given detailed instructions and templates for measurement.
Time frame: Day 1 11:45, Day 2 (24h) 11:45, Day 3 (48h) 11:45, Day 4 (72h) 11:45.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lavender | Immune Function: Delayed Hypersensitivity to Candida(DTH) | 10.84 mm^2 | Standard Deviation 10.01 |
| Water Control | Immune Function: Delayed Hypersensitivity to Candida(DTH) | 17.39 mm^2 | Standard Deviation 15.08 |
| Lemon | Immune Function: Delayed Hypersensitivity to Candida(DTH) | 12.40 mm^2 | Standard Deviation 10.12 |
Comparison: The maximum DTH wheal of days 1-3 (24, 48, or 72 h) was used as the dependent variable for each subject at each visit. Visits for subjects with a maximum DTH wheal of 5mm or less were excluded. A repeated measures linear model was used to evaluate odor and placebo effects.p-value: 0.014Regression, Linear
Primary
Skin Barrier Repair
TEWL (Transepidermal Water Loss, via tape stripping procedure)measured before and after cold pressor stressor (11:00). After obtaining baseline measurements on volar forearm, cellophane tape(3M Scotch-type; St. Paul, MN) was applied repeatedly (6-50 times) to remove superficial layer of cornified skin cells. Tape stripping stopped when TEWL was elevated from the basal level of 5-7 g/h/m2 to at least 20 g/h/m2. The number of strips required to reach TEWL X20 g/m2/h was the measure of barrier. TEWL was measured with a computerized evaporimetry instrument, the DermaLabs (CyberDERM, Media, PA).
Time frame: 3 Visits with at least 2 weeks between each. Average time to complete all visits was 64.46 days (SD 48.4).10:05, 11:45, 13:15
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lavender | Skin Barrier Repair | Time 1 Pre-Stress | 23.21 number tape strips | Standard Deviation 11.52 |
| Lavender | Skin Barrier Repair | Time 2 Post-Stress | 15.64 number tape strips | Standard Deviation 4.76 |
| Water Control | Skin Barrier Repair | Time 1 Pre-Stress | 24.33 number tape strips | Standard Deviation 10.61 |
| Water Control | Skin Barrier Repair | Time 2 Post-Stress | 17.78 number tape strips | Standard Deviation 7.3 |
| Lemon | Skin Barrier Repair | Time 1 Pre-Stress | 22.11 number tape strips | Standard Deviation 10.47 |
| Lemon | Skin Barrier Repair | Time 2 Post-Stress | 16.82 number tape strips | Standard Deviation 6.1 |
Comparison: Repeated-measures mixed effects models were used. Model was fit to the log-transformed data. Analysis applied to odor category, e.g. lavender / lemon / water.p-value: 0.6Mixed Models Analysis