The Effects of Lavender Oil Inhalation on Emotional States, Autonomic Nervous System, and Brain Electrical Activity

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Investigate the effects of lavender oil on the central nervous system, autonomic nervous system, and mood responses in humans after inhalation. Twenty healthy volunteers participated in the experiments. The present study assessed autonomic parameters such as blood pressure, heart rate, respiratory rate, and skin temperature to determine the arousal level of the autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or unpleasant, uncomfortable, sensuality, relaxation, or refreshing in order to assess subjective behavioral arousal. Finally, electroencephalogram (EEG) was recorded from 31 electrodes on the scalp according to the international 10 to 20 system, and EEG power spectra were calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the effects of lavender oil on physiological and mood states with sweet almond oil. These assessments were measured before and after using paired t-test statistical procedure. The results revealed that lavender oil caused significant decreases of blood pressure, heart rate, and skin temperature, which indicated a decrease of autonomic arousal. In terms of mood responses, the subjects in the lavender oil group categorized themselves as more active, fresher relaxed than subjects just inhaling base oil. Compared with base oil, lavender oil increased the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic map showed obviously more scattering power in alpha range waves particularly in bilateral temporal and central area. The findings provided evidence the relaxing effect of inhaling lavender oil.
598 J Med Assoc Thai Vol. 95 No. 4 2012
Correspondence to:
Ruangrungsi S, College of Public Health Sciences,
Chulalongkorn University, Bongkok 10300, Thailand.
Phone: 0-2218-8158
The Effects of Lavender Oil Inhalation on Emotional States,
Autonomic Nervous System, and Brain Electrical Activity
Winai Sayorwan MPham*, Vorasith Siripornpanich MD**,
Teerut Piriyapunyaporn BSc***, Tapanee Hongratanaworakit Dr rer nat****,
Naiphinich Kotchabhakdi PhD**,***, Nijsiri Ruangrungsi PhD*
* College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand
** Research Center for Neuroscience, Institute of Molecular Biosciences,
Mahidol University, Salaya, Nakhonpathom, Thailand
*** Salaya Stem Cell Research and Development Project, Research Center for Neuroscience, Institute of Molecular Biosciences,
Mahidol University, Salaya, Nakhonpathom, Thailand
**** Faculty of Pharmacy, Srinakharinwirot University, Nakhon-nayok, Thailand
Objective: Investigate the effects of lavender oil on the central nervous system, autonomic nervous system, and mood
responses in humans after inhalation.
Material and Method: Twenty healthy volunteers participated in the experiments. The present study assessed autonomic
parameters such as blood pressure, heart rate, respiratory rate, and skin temperature to determine the arousal level of the
autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or
unpleasant, uncomfortable, sensuality, relaxation, or refreshing in order to assess subjective behavioral arousal. Finally,
electroencephalogram (EEG) was recorded from 31 electrodes on the scalp according to the international 10 to 20 system,
and EEG power spectra were calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the effects of
lavender oil on physiological and mood states with sweet almond oil. These assessments were measured before and after
using paired t-test statistical procedure.
Results: The results revealed that lavender oil caused significant decreases of blood pressure, heart rate, and skin temperature,
which indicated a decrease of autonomic arousal. In terms of mood responses, the subjects in the lavender oil group
categorized themselves as more active, fresher, relaxed than subjects just inhaling base oil. Compared with base oil, lavender
oil increased the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic map showed obviously more
scattering power in alpha range waves particularly in bilateral temporal and central area.
Conclusion: The findings provided evidence the relaxing effect of inhaling lavender oil
Keywords: Lavandula angustifolia Mill, Physiological parameters, EEG, Relaxation
Aromatherapy can be defined as the use of
essential oils to balance mind, body, and spirit. The
word is derived from two words: aroma and therapy.
“Aroma” means smell or fragrance and “therapy” means
treatment. Complementary and alternative medicines
usually use aromatherapy in their treatments by using
essential oils usually derived from volatile liquid plant
materials and other aromatic compounds from plants(1).
In Thailand, lavender is a popular essential oil in
aromatherapy and administered by inhalation or
massage. It is also the best-selling essential oil,
particularly in Bangkok(2).
Lavenders are members of a genus Lavendula
and belong to the mint family, Lamiaceae, which is
native to the Mediterranean. In general, the essential
oil of lavender (Lavendula angustifolia Mill) consists
of linalyl acetate, β-linalool, and β-caryophyllene(3).
The general properties of lavender oil are antibacterial,
antifungal, carminative (smooth muscle relaxant),
sedative, antidepressant, promoting wound healing,
and increasing the detoxification of enzymes
associated with insecticide resistance (4). A number of
researchers report the sedative effects of lavender oil
caused by the major components linalyl acetate and
β-linalool(5,6). These compounds can be rapidly
J Med Assoc Thai 2012; 95 (4): 598-606
Full text. e-Journal:
J Med Assoc Thai Vol. 95 No. 4 2012 599
absorbed through the body by inhalation with plasma
level reaching a maximum peak in approximately seven
minutes after administration(7), which can cause a
depression of nervous system. Linalyl acetate has a
narcotic action and linalool acts as a sedative(5,6).
Diego et al (8) found that individuals felt more relaxed
and an improved mood after inhaling lavender oil.
Moreover, an increase of mid frontal (F3, F4) alpha
power on their EEG was found after inhalation of the
oil(8). Motomura(9) suggests that lavender has been
demonstrated to decrease stress scores and increase
Theta 1 (3.5-5.5Hz) brain wave activity and decrease
Beta1 (13.5-20 Hz) which is associated with relaxation
In contrast, Masago(10) found that there was a partial
decrease in alpha1 (8-11Hz) activity and a significant
decrease in posterior temporal lobe activity after
receiving lavender oil. Some researchers studying
autonomic nervous system activity also showed
contrasting results. For example, Tongnit et al(11) found
a significantly decreased blood pressure, heart rate
and respiratory rate caused by three minutes inhalation
of lavender essential oils, whereas Sriboon(12) found
inhalation lavender oil by aroma lamp caused a
significant decrease in respiratory rate and subjective
calmness and relaxation, but diastolic blood pressure
and heart rate increased. These results might be due to
hedonic effect (pleasant and unpleasant). In the
research by Brauchli et al(13), they reported that heart
rate is an autonomic variable that can be affected by
pleasant and unpleasant oils. For example, valeric acid
(judged unpleasant) can increase heart rate, while
the heart rate decreases with phenylethyl alcohol (rated
pleasant). Therefore, the differences between stimulant
aromas and sedative aromas that can affect the pattern
of heart rate are affected by two important factors, the
characteristic of the essential oil and its pleasantness.
Many researchers studied the effect of
lavender oil on the brain wave activity, the autonomic
nervous system, and mood states(5). However, these
findings were often contradictory. Furthermore, some
studies only investigated the activities in just two
dimensions(10-12). Investigations of the effects of
lavender oil in the three dimensions of brain wave
activity, the autonomic activity, and mood responses
have rarely conducted. Consequently, the present
study seems to be the first experiment to examine
the effects of lavender on central nervous system,
autonomic nervous system, such as heart rate, blood
pressure, breathing rate, and skin temperature, and
an assessment of mood states using an inhalation
Material and Method
Twenty selected participants equal number
of male and female aged between 18 and 35 years
(mean age 23.25 + 4.52 years) with normal body mass
indices (mean 20.86 + 1.91) were enrolled in the present
study. A summary of the demographic data of the
participants is presented in Table 1. All participants
were right-handed as determined by the Edinburgh
Handedness Inventory(14). None of the subjects had
abnormalities affecting smell, cardiovascular diseases,
or a history of smoking or drug addiction. Subjects
were screened for a normal sense of smell using the
n-butyl alcohol test method(15) (mean score10 + 0.77).
Twelve hours prior to testing subjects were asked to
wash their hair without any spray. They were also asked
not to use antiperspirants, perfumes and refrain from
consuming alcohol, cigarettes, or caffeinated drinks.
Women who were menstruating were not included
in the sample(16). They were requested to try to sleep
well before the day of the experiment to avoid
feeling fatigued or drowsy. Subjects were given a full
explanation of the research and a written informed
consent of all aspects of the present study, and were
free to withdraw at any time.
The present study was approved by the
Ethical Review Committee for Research Involving
Human Research Subjects, Health Science Group,
Chulalongkorn University, Permissions No. COA
Essential oil administration
The oil of lavender was obtained from the
Thai China Flavours and Fragrances Company. The oil
composition was identified by gas chromatography/
mass spectrometry (GC/MS) (Thermo Finnigan
model Trace GC Ultra equipped with Finnigan DSQ
MS detector, USA).The constituent of the oil were
identified matching their mass spectra and retention
times indicated with NIST05 MS library and the
percentage compositions were computed from GC peak
Parameters n Minimum Maximum Mean SD
Age 20 18 38 23.25 4.52
Height (cm) 20 152 17 167.43 6.82
Weight (kg) 20 46 771 58.57 6.38
Body mass index 20 17.85 24.71 20.86 1.91
Smell test 20 9 11 10.00 0.77
Table1. Demographic data for the volunteers
600 J Med Assoc Thai Vol. 95 No. 4 2012
area. Two main components of lavender oil comprised
linalyl acetate (32.46%) and linalool (31.91%).
A one-milliliter mixture of either undiluted
sweet almond oil or 10% (v/v) of lavender in base oil
was delivered using an oxygen pump system through
a plastic tube via respiratory masks in an inhalation
set for adults that permitted selective routine air
flow (2 L/min). Before the experiment, they were
asked to inhale base oil and lavender oil to rate the
pleasantness of the smell on a five-point Likert scale.
The participants, who indicated oil pleasantness
within the target level range of 2-4 were chosen to
participate in the present study.
Autonomic nervous system (ANS) and mood measure-
Mood state and ANS parameters, blood
pressure, heart rate, skin temperature, and respiratory
rate, were recorded at the same time. The ANS
parameters were measured using life scope 8 bedside
monitors (Nihon Kohden, Japan). The assessment of
mood state was based on the conceptual model
proposed by the Geneva Emotion and Odor Scale
(GEOS)(17). This scale described their subjective
affective feelings by a100 mm visual analog scale
based on the following five factors, pleasant feeling
(feel good), unpleasant feeling (feel bad, uncomfortable,
disgusted, frustrated, and/or stressed), sensuality
(romantic), relaxation (relax, serene, and drowsy), and
refreshing (refresh, energetic).
Electroencephalogram (EEG) recording
The set of 31 electrodes with 1 additional
ground which was placed according to the international
10-20 system at FP1, FP2,FZ, F3, F4, F7, F8, FT7, FC3,
FCZ, FC4, FT8, T3, T4, T5, T6, TP7, TP8, C3, CP3,
C4, CZ, CPZ, CP4, P3, P4, PZ, Ol, O2 and OZ. Both
mastoids would be used as the recording reference
(average of both mastoids, Al + A2/2). The electro-
oculogram (EOG) was monitored with four electrodes
placed in both external acanthi (HEOL and HEOR),
left supraorbital (VEOU) and infraorbital (VEOL)
regions. Electro-Caps are made of an elastic spandex-
type fabric with recessed, silver/silverchloride
(Ag/AgCl) electrodes attached to the fabric. Electrode
impedances were set below five kOhms(18). The
recording system is Acquire Neuroscan version 4.3
(Neurosoft, INC). The online filter was set to a band
pass with low pass is equal 70 Hz and high pass is
equal DC. A/D rate was 500 Hz. Gain was set at 19.
Notch filter was open at 50 Hz. The relative power
spectrum of the respective frequency bands derived
by Fast Fourier Transformation (FFT) were expressed
as follows: Delta (0-3.99 Hz), Theta (4-7.99 Hz), Alpha1
(8-9.99 Hz), Alpha2 (10-12.99 Hz) and Beta (13-30 Hz).
An A-B design was used, so that each
individual session consisted of two trails. This design
was chosen because, with olfactory stimulation, the
times court of stimulatory effects is unknown, which
might make results obtained from other designs, such
as A-B-A, difficult to interpret(19). All experiments were
conducted in a quiet room with ambient temperature
(24 + 1°C) and 40 to 50% humidity. The experiments
were performed between 8.00 and 12.00 a.m. to minimize
circadian variation. All participants attended to
this research for two times, firstly, to measure the
autonomic nervous system and mood change,
secondly, to measure brain wave. Before ANS
measurement beginning, the researcher clearly
informed the procedure, then participants signed an
Informed Consent Form describing the present study
and their rights. In addition to ANS measurement,
the ANS electrodes were attached to the appropriate
positions; the ANS parameters, i.e. heart rate, skin
temperature, and respiratory rate, were recorded at
one-minute intervals. Systolic and diastolic blood
pressure was recorded every five minutes. The tests
consisted of three trials: first session served as a
base line (resting period) and took ten minutes. After
completion of the first session, subjects were asked to
rate their mood state scales. The second and third
session took 20 minutes each. In the second, the sweet
almond oil was inhaled to the subjects, then mood state
was measured after sweet almond oil inhalation. In the
third trial, 10% (v/v) lavender oil in sweet almond oil
was applied and mood state was measured after its
inhalation. Participants were required to measure their
brainwave again after the experiment no less than
seven days. The EEG experimental conditions were
the same as autonomic nervous system experiment.
The experimental procedure was divided into four
sessions of seven minutes each. Baseline EEG
recording was done with both eyes opened and eyes
closed respectively. After that participants would be
inhaled undiluted sweet almond oil. Finally, 10%
Lavender in sweet almond oil was inhaled.
Data and statistical analysis
The SPSS statistical package 17 was used
for data analysis on the effects of lavender oil on
J Med Assoc Thai Vol. 95 No. 4 2012 601
physiological and mood states in two steps before
and after treatments by a paired t-test on blood
pressure, heart rate, skin temperature, power of brain
wave and rating of mood state. The respiratory rate
was analyzed by the nonparametric Wilcoxon sign rank
test. A p-value < 0.05 was considered significant.
Mann Whitney U-test was performed to determine the
gender different of physiological and mood effect.
Autonomic nervous system parameters
The mean and Standard Deviation (SD)
values of autonomic parameters in the experiment
are presented in Table 2. The data were compared on
various autonomic parameters during resting and
inhaling sweet almond oil. Subjects had significantly
decreased heart and breathing rates (p-value < 0.05)
during the sweet almond oil treatment compared
with those of resting. Moreover, when subjects
inhaled the lavender the systolic and diastolic blood
pressures, heart rate and skin temperature were
significantly decreased compared with sweet almond
oil inhalation.
Mood state response
The mean and SD of mood state response
are shown in Table 3. Subjects felt unpleasant when
sweet almond oil was applied, with data showing
decreased scores in good, active, fresh and relaxed
feelings. After a lavender inhalation, subjects felt they
had significant increases in pleasant emotions; good,
active, fresh, and relaxed (p-value < 0.05). Furthermore,
Parameters n Rest SO LO p-value p-value
rest and SO SO and LO
Mean SD Mean SD Mean SD (t-test) (t-test)
Systolic blood pressure (mmHg) 20 109.91 9.74 110.27 9.51 108.00 8.41 0.588 <0.001*
Diastolic blood pressure (mmHg) 20 69.32 8.76 70.26 8.96 68.52 8.43 0.527 <0.001*
Heart rate (bpm) 20 71.20 11.69 68.43 12.86 65.68 10.73 0.001* <0.001*
Skin temperature (°C) 20 31.14 1.64 31.25 1.96 31.00 1.94 0.296 0.001*
Respiratory rate (bpm) 20 18.44 9.34 15.70 2.91 16.36 6.71 0.029* 0.148
* Significant difference, p-value < 0.05
SO = sweet almond oil; LO = lavender oil
Table 2. Mean and SD of ANS parameter change during resting, sweet almond oil and lavender
Emotion n Rest SO LO p-value p-value
rest and SO SO and LO
Mean SD Mean SD Mean SD (t-test) (t-test)
Good 20 61.50 11.20 50.05 17.22 73.15 14.78 0.010* <0.001*
Bad 20 15.50 12.77 23.55 18.57 15.12 18.71 0.046* 0.085
Active 20 50.80 16.18 44.05 13.83 64.20 13.66 0.104 <0.001*
Drowsy 20 26.55 19.47 40.90 24.47 30.05 20.22 0.003* 0.047*
Fresh 20 53.45 12.68 43.35 11.12 59.40 18.18 0.004* 0.001*
Relax 20 59.15 20.97 51.55 19.26 73.65 21.41 0.243 0.004*
Stress 20 12.55 8.75 16.25 12.38 16.45 11.35 0.086 0.948
Uncomfortable 20 16.85 13.45 24.00 16.94 18.70 15.22 0.627 0.206
Romantic 20 28.78 17.43 31.35 22.86 40.55 24.38 0.709 0.151
Frustrated 20 12.51 10.15 16.40 14.77 16.55 18.38 0.094 0.976
Clam 20 62.00 18.96 54.85 19.98 61.60 20.18 0.112 0.276
Disgust 20 8.60 7.60 12.35 11.60 10.85 14.11 0.092 0.712
* Significant difference, p-value < 0.05
SO = sweet almond oil; LO = lavender oil
Table 3. Mean and SD of emotional state change during resting, sweet almond oil and lavender
602 J Med Assoc Thai Vol. 95 No. 4 2012
the bad and drowsy feelings were significantly
decreased (p-value <0.05).
EEG data
The EEG power was calculated for each
frequency band among resting, sweet almond oil,
and lavender oil inhalation. The studied areas were
divided into the left anterior (Fp1, F3, F7), right anterior
(Fp2, F4, F8), right posterior (P4, T6, O2), left posterior
(P3, T5, O1), and middle (Fcz, Cz, Cpz) (20) shown each
band power with theta, alpha1, alpha2, Beta (Table 4)
and expressed by topographic maps in Fig. 1. There
were noticeable changes of band power in theta and
alpha waves that significantly increased during the
lavender inhalation in all brains areas (p-value <0.05).
However, band powers in beta waves were not
significantly different (p-value > 0.05, data not shown).
The present study examined changes in the anterior,
posterior alpha asymmetry (left and right side) response
to sweet almond oil and lavender. There was no
significant asymmetry (p-value > 0.05) as Fig. 1. The
topographic map shows obviously more scattering
power in alpha brain, particularly in bilateral temporal
and central area after smelling lavender compared
with resting and sweet almond oil as shown in Fig. 2.
The analysis of male and female groups
Mean different score of autonomic nervous
system, mood state and power of brain during lavender
oil inhalation when compare to sweet almond oil from
10 male and 10 female group demonstrated that there
were no significant change observed between both
gender groups (p-value > 0.05, data not shown).
In the present research, lavender oil was
administered by inhalation to healthy subjects. Brain
wave activity and ANS parameters (blood pressure,
Area Eye close (n = 20) SO (n = 20) LO (n = 20) p-value p-value
mean mean mean eye close and SO SO and LO
(t-test) (t-test)
Theta power (μV2)
Left anterior 1.91 1.54 2.16 0.590 0.001*
Right anterior 2.00 1.62 2.27 0.090 0.001*
Center 2.68 2.10 3.05 0.030* 0.006*
Left posterior 1.13 1.08 1.34 0.550 0.002*
Right posterior 1.15 1.10 1.38 0.025* 0.025*
Alpha1 power (μV2)
Left anterior 3.44 3.71 6.94 0.218 0.001*
Right anterior 4.02 4.38 7.70 0.218 0.001*
Center 4.78 4.83 9.40 0.156 0.001*
Left posterior 4.16 4.56 6.86 0.218 0.001*
Right posterior 4.29 4.46 8.79 0.001* 0.001*
Alpha2 power (μV2)
Left anterior 1.51 1.43 2.09 0.911 0.011*
Right anterior 1.63 1.50 2.23 0.575 0.006*
Center 2.28 1.96 3.09 0.179 0.003*
Left posterior 2.37 2.31 3.41 0.823 0.008*
Right posterior 2.76 2.51 4.10 0.002* 0.002*
Beta power (μV2)
Left anterior 0.31 0.35 0.33 0.167 0.351
Right anterior 0.32 0.36 0.35 0.156 0.433
Center 0.36 0.41 0.41 0.086 0.627
Left posterior 0.31 0.37 0.36 0.156 0.852
Right posterior 0.31 0.36 0.37 0.794 0.794
* Significant difference, p-value < 0.05
SO = sweet almond oil; LO = lavender oil
Table 4. Mean power values in eyes closed during sweet almond oil and lavender
J Med Assoc Thai Vol. 95 No. 4 2012 603
heart rate, respiratory rate and skin temperature) were
recorded as indicators of the arousal level of the
nervous system. In addition, subjects had to rate their
mood state in terms of good, bad, active, drowsy, fresh,
relaxed, stressed, uncomfortable, romantic, frustrated,
calm, and disgusted in order to assess subjective
behavioral arousal.
Inhalation of lavender oil significantly
decreased the level of ANS arousal, namely, decreases
of blood pressure, heart rate, and skin temperature.
These changes of the ANS parameters represent the
function of parasympathetic nervous system that
counteracts the function of sympathetic nervous
system. As for mood states, subjects felt better, fresher,
more active, more relaxed, and less drowsy. This finding
points towards a decrease of arousal as assessed
through subjective self-evaluation. The results of the
present study support previous studies indicating
lavender odor can influence relaxing
Previous studies using a footbath containing
lavender oil also supports the positive effects on the
parasympathetic neural activity of lavender oil(21). To
study the underlying mechanism of lavender oil on the
nervous system, its main component, linalool, is used
as a compound to study its effects compared with
plain lavender oil. It is noteworthy that Heuberger
et al(22) found the reduction of blood pressure and
skin temperature after applying linalool to the skin of
participants. In addition, linalool has a lot of isoforms
in nature such as R)-()-, (S)-(+)- and (RS)-(+)- forms.
One study using R-()-linalool found similar effects
from this compound on the autonomic nervous
system parameters and also promoted calming and
feelings of vigor(23). According to the pharmacokinetic
properties of linalool, Yamada(24) was able to show the
lipophilic properties of the linalool was suitable for
transporting this compound across the blood-brain
barrier. When reaching the brain, linalool can bind
with the GABA (gamma aminobutyric acid) receptors
similar to the benzodiazepines and caused relaxing
and sedative effects. In one study, they found linalool
could potentiate the effects of GABA, the main
inhibitor neurotransmitters of the human brain in the
amygdala, the subcortical brain area involved in the
emotional response to the environment(25). The effect
of linalool on the amygdala may explain the mood
effects of lavender.
It is felt the effects of lavender inhalation on
the brain wave activities are well demonstrated in the
present study. During inhalation with lavender, the
power of theta (4-8 Hz) and alpha (8-13 Hz) activities
are significantly increased in all brain regions. This
result is consistent with the study of Diego(8) that
found after lavender inhalation that frontal alpha
power was significantly increased. Furthermore,
a study conducted at the University of Occupational
and Environmental Health, Kitakyushu Japan(26) used
changes of electroencephalogram (EEG) to measure
the effects of aromas. The present study found
relaxing effects with increases of alpha wave activities
after administering lavender, cineol sandalwood, and
alpha-pinene. The EEG evidence of relaxation can be
seen in various practices such as meditation.
Meditation is a way of balancing the body and the
mind as well as controlling the mind to experience
feelings of peace and relaxation. The study among
people meditating can demonstrate similar EEG
changes with lavender inhalation, which presented as
an increase in theta and alpha activities in the brain
during meditation(27). The increase in theta and alpha
activities can also be observed even during pre-
meditation states in people who frequently practice
meditation(28). These results lend support that increases
in theta and alpha wave activity causes a range of
Fig. 2 Brain Topographical map of the distribution of
alpha brainwave activity. The red areas indicate a
significantly increase of power in bilateral temporal
and central area during inhalation of lavender
Fig. 1 The power of alpha activity showed no significantly
different between left and right side of the brain
604 J Med Assoc Thai Vol. 95 No. 4 2012
general relaxation effects and can be induced by a
range of chemical and non-chemical techniques(29).
The changes in physiological and mood state
were not significant between males and females group.
This might be the effect of control pleasantness of
subjects before experiment. According to previous
studies, the hedonic impact produced effects on the
autonomic nervous system. However, to reduce
hedonic impact bias, the participants were initially
selected by measuring the degree of liking of each
essential oil. They were asked to inhale base oil and
lavender oil and to rate the pleasantness of the smell
on a five-point Likert scale. The participants, who
indicated odor pleasantness within the target level
range of 2-4, were chosen to participate in the present
study. The present study is relevant because previous
research found that a significant change for left
frontal differences in EEG were associated with the
pleasant smells. By contrast, the unpleasant smells can
also affect the brain on the right side (30). There was
no difference in EEG between left and right side when
feeling neutral to smells. Thus, according to the above
studies, they suggested that the odor liking should be
evaluated before the experiment, which could reduce
the bias from the hedonic effect.
In conclusion, the present study explored the
relaxing effects of inhaling lavender oil. The findings
provided evidence that brain wave activity, autonomic
nervous system response, and mood states were
affected by lavender oil. The results lend some support
for including lavender odor in medications aimed at
blood pressure reduction and relieving depression or
stress. For example, lavender oil decreases level of
anxiety and improves mood in dental clinics(31), after
insomnia, women inhale lavender oil significantly
improvement in sleep quality(32).
The authors wish to thank THE 90th
Anniversary of Chulalonggkorn University Fund
(Ratchadaphiseksomphot Endowment Fund) and
Herbal Remedies and Alternative Medicine Task
Force of STAR: Special Task Force for Activating
Research under 100 years Chulalongkorn University
fund for the research grant supporting the present
study. The authors wish to thank Dr. Chanida
Palanuvej and Miss Thidarat Duangyod for GCMS
protocol recommend and Dr. David Roberts for his
editorial corrections.
Potential conflicts of interest
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ผลของการสดดมนำมนลาเวนเดอร์ต่ออารมณความรู้สึก การทำงานของระบบประสาทอตโนมัติ
วินัย สยอวรรณ, วรสิทธิ์ ศิริพรพาณิชย์, ธีรัช พิริยะปัญญาพร, ฐาปนีย์ หงส์รัตนาวรกิจ, นัยพินิจ คชภักดี,
นิจศิริ เรองรงษ
วัตถุประสงค์: เพื่อทดสอบผลของน้ำมันลาเวนเดอร์ที่มีต่อระบบประสาทซึ่งแบ่งเป็นประสาทส่วนกลาง และประสาท
ส่วนอัตโนมัติ และการตอบสนองของอารมณ์ความรู้สึกหลังจากการสูดดม
วัสดุและวิธีการ: การศึกษาครั้งนี้อาสาสมัครสุขภาพดีจำนวน 20 คน การศึกษาครั้งนี้ทดสอบการเปลี่ยนแปลง
ในระบบประสาทอัตโนมัติโดยศึกษาการเปลี่ยนแปลง ของความดันโลหิต, การเต้นของหัวใจ อัตราการหายใจ และ
อุณหภูมิที่ผิวหนัง นอกจากนี้ยังศกษาอารมณความรู้สึกโดยแบงเปนดาน ไดแก ความชอบในกลิ่น, ความไมชอบในกลิ่น
ความดงดดทางเพศ การผอนคลาย และความสดชื่น ในระบบประสาทสวนกลางมการศกษาการเปลี่ยนของคลื่นสมอง
โดยบันทึกคลื่นสมองทั้งหมด 31 จุดทั่วศีรษะ โดยบันทึกข้อมูลทั้งความถี่และค่าฟูเรียร์ทรานส์ฟอร์มอย่างเร
ซึ่งข้อมูลเปรียบเทียบผลการเปลี่ยนแปลงทางสรีรวิทยา และอารมณ์ความรู้สึกเมื่อสูดดม น้ำมันลาเวนเดอร เทียบกับ
สูดดมนำมนอลมอนด โดยใชสถิติ paired t-test
ผลการศึกษา: กลิ่นลาเวนเดอร์ทำให้ ความดันโลหิต การเต้นของหัวใจ และอุณหภูมิที่ผิวหนังลดลงเป็นการแสดงถึง
การลดการทำงานของระบบประสาทอัตโนมัติ ในส่วนของอารมณ์ความรู้สึกอาสาสมัคร รู้สึกว่าตนเองมีความรู้สึก
กระตอรอร้น รู้สึกสดชื่น และผอนคลายมากกวาดมกลิ่นนำมนอลมอนด นอกจากนี้ยังพบว่า มีการเพิ่มของคลื่นสมอง
ประเภทธีต้า และแอลฟาอยางเหนได้ชัดเจน จากภาพถายคลื่นสมองพบวาสมองสวน temporal และ central แอลฟา
สรุป: ผลการศึกษาครั้งนี้สนับสนุนผลการการผ่อนคลายของการสูดดมน้ำมันลาเวนเดอร
  • ... Additionally, lavender essential oil reduces high cortisol levels and blood pressure in patients with essential or idiopathic hypertension [10][11][12][13][14][15][16][17][18]. Moreover, lavender essential oil promotes relaxation [12], benefits the coronary circulation [19] and decreases heartbeat and skin temperature [20]. The same effects were observed in patients in dental treatment [21] and in intensive care units [22]. ...
    Introduction Chronic stress and sleeping disorders have long been associated with anxiety. Pharmacological treatment includes benzodiazepines and selective serotonin reuptake inhibitors. The adverse effects associated with these medicines do, however, call for safer alternatives, including aromatherapy. The current study assesses the effect of intranasal administration of essential oils obtained from lavender, French lavender and fennel (Pinetonina™), on chronic stress. Methods Forty-five patients were divided in 3 groups: Group 1 (CTRL) received saline in nasal spray form; Group 2 (P30) received 30 % Pinetonina™ in buffered vehicle for intranasal spray; Group 3 (P50), 50 % Pinetonina™ in the same vehicle. All groups used the product for 3 months, once daily (before bedtime), using a spray-puff in each nostril. Salivary cortisol levels were measured in the beginning and at the end of the study. Quality of sleep, level of anxiety, perceived stress, and overall quality of life were measured through self-reported questionnaires. Results In P30 and P50, total salivary cortisol levels were significantly reduced by 37 % and 54 % respectively. Changes in perceived stress and overall quality of life showed no significant differences among the 3 groups, but P50 showed significant improvement in the quality of sleep index, as evaluated with the PSQI questionnaire. Salivary cortisol levels at time-zero and after 3 months of use were compared. Significant changes in the salivary cortisol levels for 30 % and 50 % of Pinetonina were seen after 3 months, unlike the control that showed no significant changes. Additionally, the Pittsburgh Sleep Quality Index when compared at baseline with the end of the study for the placebo and 30 % and 50 % Pinetonina. Significant changes in the quality of sleep were shown. Conclusions Daily intranasal use of Pinetonina™ before sleep was shown to significantly reduce salivary cortisol levels and improve quality of sleep based upon the significant differences found in the study.
  • Article
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    Background: Stroke is the third leading cause of death and the primary cause of serious, long-term disability which can be regarded as weakness, generalized fatigue, loss of voluntary motor control or limitation in mobility, spasticity, sensory and cognitive dysfunction. In this research, a comparative study on the ability of independent self-care was conducted between two groups of patients during a 3 months follow-up period viz. Group A - patients who were given Home Exercise Programme (HEP) with conventional physiotherapy; and Group B - patients who were given HEP with conventional physiotherapy along with neuro-facilitation via Rood’s approach.Methods: In this study 236 haemorrhagic stroke patients were recruited and randomly divided to two groups. Both the groups were given a HEP consisting of regular physiotherapy. Additionally, one group out of the two was also taught exercises based on Rood’s approach consisting of facilitation and inhibition with the help of sensory stimulation, purposeful activity based exercises, with additional emphasis on repetition. The output was evaluated in terms of disability using the Barthel Index after 3 months of treatment.Results: After 3 months, it was found that patients who received HEP with both conventional physiotherapy and Rood’s approach had significantly greater improvement in Barthel Index scores compared to patients who received HEP only through conventional physiotherapy.Conclusions: This suggests that HEP consisting of conventional physiotherapy along with Rood’s approach is more effective in improving the ability of independent self-care in case of post intra-cerebral haemorrhagic patients when compared to conventional physiotherapy alone.
  • Article
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    Abstract Purpose: This study aimed to examine potential differences in electroencephalogram (EEG) activity according to workload stress suffered by medical professionals in our institute, King Fahad Medical City (KFMC) in Riyadh, Kingdom of Saudi Arabia (KSA) during working days relative to non-working days. Methods: A prospective cohort study of 73 medical professionals from KFMC was conducted. EEG recordings were gathered twice per participant-once during working (stress) day and again during the non-working (rest) day. Results: The p-value was calculated as 0.988. A positive relationship between EEG activity during days of work and that found during non-working days could not be established in our cohort study. Conclusion: In our study, no evidence of a positive relationship was found between EEG findings in medical professionals on high-stress working days compared to low-stress non-working days. This does not exclude the possibility of presence of a true relation, as the period between the EEGs done on duty days and off days was short and not allowing for relief and relaxation effects to occur. Keywords: Potential differences; Electroencephalogram; Relaxation effects; Psychological stress; Behavior; Cognitive processes; Systemic diseases; Psychological; Metabolic diseases; Institutional Review Board; Polyrhythmic
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    Fragrance inhalation of essential oils is widely used in aromatherapy, and it is known to affect blood pressure (BP) and heart rate (HR) via autonomic control of circulation. In this study, we aimed to test the hypothesis that the changes in hemodynamics with fragrance inhalation were observed along with changes in muscle sympathetic nerve activity (MSNA). In study 1, thirteen healthy men were exposed to fragrance stimulation of grapefruit essential oil for 10 min, and BP, HR, and MSNA were continuously measured. In study 2, another nine healthy men were exposed to the same fragrance stimulation; responses in BP and HR were continuously measured, and plasma noradrenaline and cortisol concentrations were determined. We found that diastolic BP increased significantly during fragrance inhalation, while the other variables remained unchanged in both studies. Although MSNA burst frequency, burst incidence, and total activity remained unchanged during fragrance inhalation, we found a significant linear correlation between changes in diastolic BP in the last 5 min of fragrance inhalation and changes in MSNA burst frequency. The plasma cortisol concentration decreased significantly at 10 min of fragrance inhalation, though the noradrenaline concentration remained unchanged. These results suggest, for the first time, that changes in BP with fragrance inhalation of essential oil are associated with changes in MSNA even with decreased stress hormone.
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    Chemicals used in laboratories may pose health threats to individuals handing them. This work was carried out to evaluate the effect of chloroform inhalation on the hippocampus of Wistar rats. Fourteen male Wistar rats weighing 150-180g were divided into two groups of 7 rats each. Group A was the control group and Group B was the experimental group which was exposed to 50ml of chloroform for 5minutes daily in an inhalation chamber for 14 days. Neurobehavioral study was done before and after exposure and the rats were sacrificed. Two rat brains were fixed in Bouin's fluid for histological studies and the other five for antioxidant studies. Results were analyzed using SPSS and values were significant at P≤0.05. Results reveal the animals in group B were under oxidative stress compared to those in control. Although rat weight increased in the 2 groups, the percentage increase was lower in the experimental group B compared to control. Histological analysis showed varying degrees of necrosis in the hippocampus of group B rats. Neurobehavioral studies revealed significant increase in the time to discover the escape platform compared to control. We therefore infer that chloroform inhalation has neurodegenerative effects on the hippocampus of Wistar rats.
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    This study investigates chemical composition and antimicrobial activity of essential oil of Lavandula officinalis from Montenegro, Mediterranean, and effects on autonomic nervous system. The oil was analysed by GC-MS technique in order to determine the majority compounds while dilution method was used to determine minimal inhibitory concentration. The present study assessed autonomic parameters such as blood pressure, heart rate, and skin temperature to determine the arousal level of the autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or unpleasant, uncomfortable, sensuality , relaxation, or refreshing in order to assess subjective behavioural arousal. Chemical analysis by GC-MS identified 31 compounds in lavender oil representing 96.88% of the total oil. Linalool (24.84%), was a major component, together with linalyl acetate (22.39%), 1,8 cineole (18.13%) and camphor (12.88%). The investigated lavender oil consisted mostly of oxygenated monoterpenes (87.95%) and monoterpene hydrocarbons (7%). The lavender oil exhibited antimicrobial activity against Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 19111), Proteus mirabilis (ATCC 25933) and Candida albicans (ATCC 10231) with an MIC of 1.4µl/ml. The results revealed that lavender oil caused significant decreases of blood pressure and heart rate, which indicated a decrease of autonomic arousal.
  • Article
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    Idiopathic normal pressure hydrocephalus (iNPH) is a chronic disease in adults. The standard treatment in this type of hydrocephalus is shunting which is accompanied by some complications and there is also uncertainty about response to treatment. Therefore, surgery is performed in only 10-20% of the cases with iNPH. Currently, oral acetazolamide and repetitive lumbar puncture for drainage of the cerebrospinal fluid are recommended in many patients. In this case report, a 34-year-old female patient with iNPH is introduced who received acetazolamide for the past two years, and repetitive lumbar punctures. These treatments reduced her symptoms for a short time, but had never disappeared the symptoms and after a while they intensified again. The patient was treated by Persian medicine and nutrition modification was also done. Within one year, there was no recurrence of the disease and no need for lumbar puncture. This case report highlights the need for further research on Persian medicine in treatment of iNPH. It is believed that Persian medicine could be of great benefit along with current treatments of hydrocephalus. Keywords: idiopathic normal pressure hydrocephalus, treatment, Persian medicine J Mazandaran Univ Med Sci 2019; 29 (172): 153-159 (Persian).
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    Background: Olfactory system regulates the brain which controls emotional memory. Coffee is one of the most consumed beverages in the world. Drinking coffee shows beneficial effects for mood, memory, and psychomotor performance. This work aimed to determine the effects of inhaling coffee fragrance on memory, mood, and salivary cortisol level in healthy young volunteers. Methods: Eighty young males and females, aged between 18-22 years old, were randomly assigned into two groups: a placebo group inhaling scent from carbon powder and a coffee fragrance group inhaling coffee fragrance. Subjects were assigned to inhale either placebo or coffee fragrance for five minutes. Before and after inhalation period, the clinical assessments were assigned to each subject including computerized assessment battery test for cognitive performance, and self-related visual analogue mood scales for evaluation of mood score. The salivary cortisol level was assessed with cortisol ELISA kit. In addition, the blood pressure and heart rate were also evaluated. Results: Inhalation of coffee fragrance enhanced cognitive parameters, including continuity of attention, quality of memory, and speed of memory, and also increased the mood score of alertness. However, there were no significant changes in salivary cortisol level, blood pressure, and heart rate between pre-and post-inhalation. Conclusions: One time of coffee fragrance inhalation may enhance working memory and stimulates alertness. However, inhaling coffee fragrance does not reduce stress or modulate autonomic response to stress.
  • Article
    Objectives:This study was designed to investigate the effect of foot-bath with or without the essential oil of lavender on the autonomic nervous system. Design: Randomized crossover controlled study. Setting: Nursing college, Nagano, Japan. Intervention:Young women sat with their feet soaked in hot water for 10 minutes with and without the essential oil. Outcome measures:An electrocardiogram, finger tip blood now and respiratory rate were recorded,Autonomic function was evaluated using spectral analysis of heart rate variability. Results:The foot-bath caused no changes in heart or respiratory rates, but produced a significant increase in blood now. Using spectral analysis, the parasympathetic nerve activity increased significantly during the both types of foot-bath. In the case of the foot-bath with the addition of essential oil of lavender, there were delayed changes to the balance of autonomic activity in the direction associated with relaxation. Conclusion:A hot foot-bath and oil of lavender appear to be associated with small but significant changes in autonomic activity. (C) 2000 Harcourt Publishers Ltd.
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    Lavender essential oil is popular as a complementary medicine in its own right and as an additive to many over the counter complementary medicine and cosmetic products ' \ Indeed, products derived from the popular garden herb Lavender (Lavandula spp.) have been used for centuries as a therapeutic agent, with the more 'recent ' addition, the essential oils derived from these plants, being widely used as an antibacterial in World War I),! The oil is traditionally believed to have sedative, carminative, anti-depressive and anti- inflammatory properties, in addition to its recognised antimicrobial effects. Many of the activities attributed to lavender oil have not, however, been substantiated in the scientific literature. This is further complicated by the fact that the majority of research into lavender essential oils has been based on oil derived from English lavender (Lavandula angustifolia), with little or no differentiation being made between this and other lavender essential oils. The therapeutic potential of essential oils produced from other varieties, such as L. x intermedia (lavandin), L. stoechas (French lavender) and L. x allardii, have largely been ignored. Although the ethnobotanical uses and major chemical constituents are similar between various lavenders, some differences do occur in both oil composition and in the reported therapeutic uses for different ~pecies~,~. The significant scientific interest in recent years into the validity/veracity of the traditional beliefs surrounding lavender oil and their scientific basis, if any, was recently reviewed by Cavanagh & Wilkinson? In this paper we provide an overview of the use of lavender oil in infectious disease and an update on recent research on alternative uses of lavender oil. Lavender oil (primarily L. angustifolia) has been found to be active against many species of bacteria, including those resistant to antibiotics such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) b~R. Recent investigations into the antibacterial properties of a range of Lavandula oils (L. angustifolia, L. allardii, L. x intermedia 'Grosso', L. x intermedia 'Seal', L. x intermedia 'Miss Donnington', L. x heterophylla and L. stoechas 'Avonview') support the anecdotal use of lavender oils as antibacterial agents and demonstrated that Despite the known antibacterial activity, questions remain about the clinical utility of lavender oil. The MIC (minimum inhibitory concentration) values of lavender oil (L. angustifolia and L. latifolia) have been reported as being comparable to that of tea tree oil (0.16% against Haemophilus influenzae, 0.32% against S. pyogenes and S. aureus and greater than 0.32% against E. ~oli)'~. These figures would appear to support the use of lavender oils as a prophylactic or for use in topical application for surface infection rather than for use against deep-seated infections. some oils which had previously not been investigated (e.g. L. Lavender oil has also been reported to be an effective antifungal heterophylla) displayed good antibacterial activity against a range agent against fungi of both medical and agricultural importance, of bacteria including Streptococcus pyogenes, Enterobacter aerogenes, especially in inhibition of germ-tube growth ". A recent study S. aureus, MRSA, Pseudomonas aeruginosa, Citrobacter freundii, demonstrated that all Lavandula essential oils examined to date Proteus vulgaris, Escherichia coli, VRE, Shigella sonnei and displayed some antifungal activity, with oils derived from L. Propionibacterium acnes 9. an~ustifolia and L. x intermedia demonstrating the greatest effect -. Interestingly, there was considerable variability in the activity of against Aspergillus nidulans and Trichophyton mentagrophytes. the essential oils, with L. angustifolia and L. x intermedia oils In contrast, oil derived from L, stoechas was particularly effective showing the highest activity against several bacteria. However, against the agricultural fungi Leptosphaeria maculans and Sclerotinia no one oil produced the highest level of antibacterial activity sclerotiorum, demonstrating that Lavandula oils have activity against all bacteria tested, suggesting that differences in chemical against fungi of both medical and agricultural importance, and composition make some oils more effective against particular suggesting that essential oils from various lavender varieties may bacteria. No strong correlation has been observed between be useful in the treatment of fungal infections ''. percentage of major chemical components and antibacterial activity, and P aeruginosa was not susceptible to any Lavandula oil The recent interest in the therapeutic use of hydrosols, however, tested9. These results support the anecdotal use of lavender oils appears unlikely to have scientific merit as no antimicrobial as antibacterial agents and demonstrate that some oils which had activity has been found to be associated with any Lavandtlla previously not been investigated have good antibacterial activity. hydrosols examined by this group to date 12. Hydrosols or
  • Article
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    The objective of this study is to determine the effects of 12 weeks of lavender aromatherapy on self-reported sleep and heart rate variability (HRV) in the midlife women with insomnia. Sixty-seven women aged 45-55 years, with a CPSQI (Chinese version of Pittsburgh Sleep Quality Index) greater than 5, were recruited from communities in Taiwan. The experimental group (n = 34) received lavender inhalation, 20 min each time, twice per week, for 12 weeks, with a total of 24 times. The control group (n = 33) received health education program for sleep hygiene with no intervention. The study of HRV was analyzed by time- and frequency-domain methods. Significant decrease in mean heart rate (HR) and increases in SDNN (standard deviation of the normal-to-normal (NN) intervals), RMSDD (square root of the mean squared differences of successive NN intervals), and HF (high frequency) of spectral powers analysis after lavender inhalation were observed in the 4th and 12th weeks of aromatherapy. The total CPSQI score of study subjects was significantly decreased in the experimental group (P < 0.001), while no significant difference was observed across the same time period (P = 0.776) in the control group. Resting HR and HRV measurements at baseline 1 month and 3 months after allocation showed no significant difference between the experimental and control groups. The study demonstrated that lavender inhalation may have a persistent short-term effect on HRV with an increase in parasympathetic modulation. Women receiving aromatherapy experienced a significant improvement in sleep quality after intervention. However, lavender aromatherapy does not appear to confer benefit on HRV in the long-term followup.
  • Article
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    To evaluate the effect of the odor of incense on brain activity, electroencephalograms (EEGs) and event-related potentials (ERPs) in a push/wait paradigm were recorded in 10 healthy adults (aged 23-39 years) with normal olfactory function. EEG was recorded from 21 electrodes on the scalp, according to the International 10-20 system, and EEG power spectra were calculated by fast Fourier transform for 3 min before and during odor presentation. ERPs were recorded from 15 electrodes on the scalp before, during and after exposure to incense with intervals of 10 min. In a push/wait paradigm, two Japanese words, 'push' as the go stimulus and 'wait' as the no-go stimulus, appeared randomly on a CRT screen with equal probability. The subjects were instructed to push a button whenever the 'push' signal appeared. Fast alpha activity (10-13 Hz) increased significantly in bilateral posterior regions during incense exposure compared to that during rose oil exposure. The peak amplitudes of no-go P3 at Fz and Cz were significantly greater during incense inhalation. The latencies of go P3 and no-go P3, and the amplitude and latencies of no-go N2 did not change by exposure to the odors of both incense, rose and odorless air. These results suggest that the odor of incense may enhance cortical activities and the function of inhibitory processing of motor response.
  • Article
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    Two studies were conducted to examine the nature of the verbal labels that describe emotional effects elicited by odors. In Study 1, a list of terms selected for their relevance to describe affective feelings induced by odors was assessed while participants were exposed to a set of odorant samples. The data were submitted to a series of exploratory factor analyses to 1) reduce the set of variables to a smaller set of summary scales and 2) get a preliminary sense of the differentiation of affective feelings elicited by odors. The goal of Study 2 was to replicate the findings of Study 1 with a larger sample of odorant samples and participants and to validate the preliminary model obtained in Study 1 by using confirmatory factor analysis. Overall, the findings point to a structure of affective responses to odors that differs from the classical taxonomies of emotion such as posited by discrete or bidimensional emotion theories. These findings suggest that the subjective affective experiences or feelings induced by odors are structured around a small group of dimensions that reflect the role of olfaction in well-being, social interaction, danger prevention, arousal or relaxation sensations, and conscious recollection of emotional memories.
  • Article
    The aim of the study was to find correlations between changes in olfactory sensitivity and the menstrual cycle. 14 young, healthy volunteers participated in the experiments. Subjects menstruated regularly and did not use oral contraceptives. Three odorants were investigated: phenylethyl alcohol, androstenone, and nicotine. Dilution series of the odorants were prepared, and presented to the subjects in order to determine the detection thresholds (triple forced choice). Additionally, the subjects' hedonic estimates of the odorants were measured, and mood states as well as hormonal levels of LH and estrogen were determined. Before the actual experiments started, subjects participated in three training sessions. One experiment was subdivided into 5 phases (two pre- and two postovulatory phases; one ovulatory phase). Only with regard to androstenone did trend analyses reveal a significant quadratic relationship between hedonic estimates and phases of the menstrual cycle, peaking at ovulation. Olfactory sensitivity was not significantly influenced by the menstrual cycle.
  • Article
    Assessment of olfactory functioning at the CCCRC entails a threshold test and an odor identification test that contains eight everyday items. A performance average on the two tests yields a composite score on a scale from 0 (anosmia) to 7 (normosmia). The performance of normal volunteers is stable over most of an individual's life span, but decreases for persons over the age of 65 years. Approximately half the patients with olfactory complaints display anosmia, and the other half have hyposmia. The distribution of scores, however, varies with etiologic category, emplified by the fact that patients with nasal/sinus disease display anosmia more frequently than hyposmia. The tests can determine cause (e.g., improvement of score with corticosteroid treatment in cases of nasal/sinus disease) and can also assess degree of improvement with treatment, such as sinus operation.
  • Article
    In the present experiment, we found that inhaling lavender oil vapour blocked pentetrazol- and nicotine-induced convulsion and electroshock convulsion in mice.