which the Rapporteur and the MLWP will take into consideration but no ‘overview of comments
received during the public consultation’ will be prepared in relation to the comments that will be
received on this assessment report. The publication of this
draft
assessment report has been agreed to
facilitate the understanding by Interested Parties of the assessment that has been carried out so far
and led to the preparation of the draft monographs.
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 2/45
Table of contents
Table of contents
................................................................................................................... 3
1. Introduction....................................................................................................................... 4
1.3. Search and assessment methodology....................................................................
8
2. Historical data on medicinal use ........................................................................................ 9
2.1. Information on period of medicinal use in the Community ........................................
9
preparations and indications..................................................................................... 1
0
3. Non-Clinical Data ............................................................................................................. 12
preparation(s) and relevant constituents thereof ......................................................... 1
2
preparation(s) and relevant constituents thereof ......................................................... 2
2
preparation(s) and constituents thereof ..................................................................... 2
2
3.4. Overall conclusions on non-clinical data............................................................... 2
3
4. Clinical Data ..................................................................................................................... 24
4.1. Clinical Pharmacology ....................................................................................... 2
4
including data on relevant constituents ...................................................................... 2
4
including data on relevant constituents ...................................................................... 3
0
4.2. Clinical Efficacy ................................................................................................ 3
1
4.2.1. Dose response studies.................................................................................... 3
1
4.2.2. Clinical studies (case studies and clinical trials).................................................. 3
1
4.2.3. Clinical studies in special populations (e.g. elderly and children)........................... 3
9
4.3. Overall conclusions on clinical pharmacology and efficacy ...................................... 4
3
5. Clinical Safety/Pharmacovigilance................................................................................... 43
5.1. Overview of toxicological/safety data from clinical trials in humans.......................... 4
3
5.2. Patient exposure .............................................................................................. 4
4
5.3. Adverse events and serious adverse events and deaths ......................................... 4
4
5.4. Laboratory findings .......................................................................................... 4
4
5.5. Safety in special populations and situations ......................................................... 4
4
5.6. Overall conclusions on clinical safety ................................................................... 4
4
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 3/45
1.
Introduction
1.1.
Description of the herbal substance(s), herbal preparation(s) or
combinations thereof
Herbal substance(s)
Lavender flower consists of the dried flowers of
Lavandula angustifolia
Miller (
Lavandula officinalis
Chaix) (European Pharmacopoeia 2008a).
Herbal preparation(s)
Essential oil obtained by steam distillation from the flowering tops of
Lavandula angustifolia
Miller
(
Lavandula officinalis
Chaix) (European Pharmacopoeia 2008b).
The species is regularly confused with other lavender species
L. x intermedia
Emeric. (Lavandin) and
L.
latifolia
MEDIK. (Spiklavender). If no detailed quality specifications are mentioned, the herbal
substance consists of flowers from different flower species (Hänsel et al. 1993).
Combinations of herbal substance(s) and/or herbal preparation(s) including a description of
vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products
assessed, where applicable.
Not applicable.
Constituents
Lavender flower contains not less than 13 ml/kg of essential oil, calculated with reference to the dried
drug.
Lavender flower
- Essential oil (1-3%)
- Coumarin derivatives: umbelliferon, herniarine
- Flavonoids
- Sterols (traces): cholesterol, campesterol, stigamsterol, β-sitosterol
- Triterpenes (traces): mictomeric acid, ursolic acid
- Tannins: up to 13% in the herbal substance
- Phenylcarboxylic acids such as rosmarinic acid, ferulic acid, isoferulic acid, α-cumaric acid, p-cumaric
acid, gentisinic acid, p-OH-benzoic acid, caffeic acid, melilotic acid, sinapinic acid, sytingic acid,
vanillinic acid.
Lavender oil
The main components of the essential oil are monoterpene alcohols (60-65%) such as linalool (20-
50% of the fraction), linalyl acetate (25-46% of the fraction).
Others include cis-ocimen (3-7%), terpinene-4-ol (3-5%), limonene, cineole, camphor, lavandulyl
acetate, lavandulol and α-terpineol, β-caryophyllene, geraniol, α-pinen.
Non-terpenoid aliphatic components: 3-octanon, 1-octen-3-ol, 1-octen-3-ylacetate, 3-octanol. (ESCOP
2009; Hänsel et al. 1993; Bruneton 1999).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 4/45
1.2.
Information about products on the market in the Member States
Regulatory status overview
Member State Regulatory Status
Comments
Austria
MA
TRAD
Other TRAD
Other Specify: See composition
Belgium
MA
TRAD
Other TRAD
Other Specify: No monopreparations
registered
Bulgaria
MA
TRAD
Other TRAD
Other Specify: No information
Cyprus
MA
TRAD
Other TRAD
Other Specify: No information
Czech Republic
MA
TRAD
Other TRAD
Other Specify: No monopreparations
registered
Denmark
MA
TRAD
Other TRAD
Other Specify: Only flowers in herbal
tea
Estonia
MA
TRAD
Other TRAD
Other Specify: No registered products
on the market
Finland
MA
TRAD
Other TRAD
Other Specify: No registered products
on the market
France
MA
TRAD
Other TRAD
Other Specify: Only combined
preparations registered
Germany
MA
TRAD
Other TRAD
Other Specify: See detailed
information
Greece
MA
TRAD
Other TRAD
Other Specify: No registered products
on the market
Hungary
MA
TRAD
Other TRAD
Other Specify:
Iceland
MA
TRAD
Other TRAD
Other Specify: No information
Ireland
MA
TRAD
Other TRAD
Other Specify: No information
Italy
MA
TRAD
Other TRAD
Other Specify:
Latvia
MA
TRAD
Other TRAD
Other Specify: No information
Liechtenstein
MA
TRAD
Other TRAD
Other Specify: No information
Lithuania
MA
TRAD
Other TRAD
Other Specify: No information
Luxemburg
MA
TRAD
Other TRAD
Other Specify: No information
Malta
MA
TRAD
Other TRAD
Other Specify: No registered products
on the market
The
Netherlands
MA
TRAD
Other TRAD
Other Specify:
Norway
MA
TRAD
Other TRAD
Other Specify: No registered products
on the market
Poland
MA
TRAD
Other TRAD
Other Specify:
Portugal
MA
TRAD
Other TRAD
Other Specify:
Romania
MA
TRAD
Other TRAD
Other Specify: No information
Slovak
MA
TRAD
Other TRAD
Other Specify:
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 5/45
Member State Regulatory Status
Comments
Republic
Slovenia
MA
TRAD
Other TRAD
Other Specify:
Spain
MA
TRAD
Other TRAD
Other Specify:
Sweden
MA
TRAD
Other TRAD
Other Specify: No registered products
on the market
United
Kingdom
MA
TRAD
Other TRAD
Other Specify:
MA: Marketing Authorisation
TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration
Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the
products in the MSs concerned.
Composition of preparations
Member State Regulatory Status
Comments
Austria
BUCOSEPT Lavendel–Ölbad
100 g solution contains 5 g essential oil from
Lavandula
angustifolia.
Posology
For a full bath 30 ml of the solution; duration of bath 15-
20 minutes.
Indication
Supportive in case of exhaustion.
On the market since
1994
Denmark
2 products with Lavandulae herba as one of the
components in herbal tea.
On the market since
1999
France
Aromastress oleocapsule aromatique
(Pranârom–
Natessence)
Essential oils of
Origanum majorana
,
Lavandula hybrida
,
Citrus reticulata
,
Aloysia triphylla
Indication
Stress, nervousness
Climarome voies respiratoires
(Cosbionat) Essential
oils of
Lavandula angustifolia
,
Melaleuca viridiflora
,
Pinus
sylvestris
,
Mentha arvensis
,
Thymus vulgaris
33.6% -
excipients qsp 100.
Indication
Prevention of respiratory tract infections.
Adults and children
>
3 years: to be applied on tissue for
inhalation or to be put on the throat or the thorax.
Perubore spray aromatique
(Mayoli spindler): essential
oils of
Thymus vulgaris, Rosmarinus officinalis, Lavandula
officinalis, Cinnamomum zeylanicum
.
Indication
Capsule as food
supplement.
>30 years on the
market
>30 years on the
market
>30 years on the
market
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 6/45
Member State Regulatory Status
Comments
Cough, common cold, nose congestion.
Adults and children >30 months: vaporise 2 to 3 puffs in
the atmosphere or on tissue when the first symptoms of
common cold occur. To be repeated several times daily. At
nighttime 2 to 3 puffs on the pillow.
Vivalessence
(Motima) Essential oils of
Lavandula,
Cinnamomum, Satureja, Eucalyptus
4.8%, hydroalcoolic
extract of
Avena
, ethanol – water qs. ad 100%.
Indication
Seasonal complaints.
Adults, children >7 year:
Seasonal complaints: during 15 days 30 to 50 drops daily
in a glass of water (in the morning).
Tetesept anti-stress Bad
(Merz Pharma) essential oils of
Lavandula, Melissae indicum, Pinus, Rosmarinus.
Indication
No indication mentioned.
To be put in a bath.
Tetesept Entspannungs Bad
(Merz Pharma) essential
oils of:
Citrus aurantium spp., Cinnamomum, Lavandula
Indication
No indication mentioned.
To be put in a bath.
>30 years on the
market
On the market since
1996
On the market since
1983
Germany
Lavandulae aetheroleum
In soft capsules containing 80 mg Lavandulae aetheroleum
Indication
For treatment of anxious restlessness or
For treatment of restlessness due to anxiety
(
…zur Behandlung von Unruhezuständen bei ängstlicher
Verstimmung ...
)
Posology
1x1 capsule per day
For oral use in adults over 18 years
Specific information
Possible influence on medicinal products, which act via
GABA-receptors (barbiturates, benzodiazepine). Clinical
data are not available.
Adverse events: eructation (7%); nausea (2%)
No use in children and adolescents below the age of 18
years.
Up to now, there was no need to undertake
pharmacovigilance actions.
Lavandulae aetheroleum
All as bath additive
Indication
Traditionally used to improve feeling in state of exhaustion
(…Traditionell angewendet zur Besserung des Befindens
Authorized product
since 2009
WEU
Authorized product at
least since 1976
TU
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 7/45
Member State Regulatory Status
Comments
bei Erschöpfungszuständen …)
Posology
For use in adults and adolescents over 12 years
1) 15-20 ml bath additive / full bath at 35-38° for 10-20
minutes
7 g Lavandulae aetheroleum / 100 g (= approximately
96 ml) bath additive
2) 15-20 ml bath additive / full bath at 35-38° for 10-20
minutes
7 g Lavandulae aetheroleum / 100 g (=95 ml) bath
additive
3) 30 ml bath additive / 150-200 l water at 35-37° for 15-
20 minutes
10 g Lavandulae aetheroleum / 100 g bath additive
Specific information
General contraindications to take a bath.
Up to now, there was no need to undertake
pharmacovigilance actions.
Combined products
There are 5 authorized products on the market
number of
combination substances
Authorized products
number of authorized
combination products
2-3
0
4-5
1
>5
4
1.3.
Search and assessment methodology
For this assessment report the following sources were used:
- Allied and alternative medicine
- Biosis
- Chemical abstracts (since 1967)
- Current contents search - bibliographic records
- Derwent drug file
- Derwent drug file backfile
- Excerpta Medica
- International pharmaceutical abstracts
- Medline
- Pascal
- PubMed
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 8/45
- Standard reference books
These sources were searched on the following terms (alone or in combination):
Lavandula, lavender, essential oil, stress, anxiety, relaxation, sleep, sleeping, disorder
2.
Historical data on medicinal use
2.1.
Information on period of medicinal use in the Community
In the 15
th
century when the technique of steam distillation was developed, Hildegarde von Bingen and
Paracelsus described the use of distilled water saturated with the essential oil of lavender as a
sedative. The oil was traditionally used by evaporating it into rooms to calm ‘excited’ children. Even
narcotic effects have been described when high concentrations were used (Guillemain et al. 1989).
Rembertus Dodonaeus (1608) mentioned already the use of lavender water as a calming agent, even
in case of epileptic seizures. Flowers and essential oil of
Lavandula officinalis
have been used for their
sedative activity throughout Europe (Weiss & Fintelmann 1999). Leclerc (1966) has mentioned the use
of lavender flowers in phytotherapeutic practice in France.
According to information on marketed products, lavender oil has been marketed for topical use since
1976. Since 2009, soft capsules with lavender oil have been marketed as an authorized product in
Germany. This practice has been preceded by a long-standing tradition of administering the essential
oil as drops on a piece of sugar (ESCOP 2009; British Herbal Pharmacopoeia 1983, referring to the
British Pharmaceutical Codex 1973).
2.2.
Information on traditional/current indications and specified
substances/preparations
Peroral use
Soft capsules with Lavandulae aetheroleum have been authorized in Germany since 2009.
- Therapeutic indications: WEU
For treatment of anxious restlessness or for treatment of restlessness due to anxiety.
(
…zur Behandlung von Unruhezuständen bei ängstlicher Verstimmung ...
)
- Posology
For adults ≥ 18 years: soft capsules containing 80 mg, 1 capsule per day.
Use as bath additive
Bath additives with Lavandulae aetheroleum have been authorized in Germany since at least 1976.
- Therapeutic indications: TU
Herbal medicinal product traditionally used to improve feeling in state of exhaustion.
- Posology
For adults and adolescents over 12 years: 15 to 30 ml bath additive containing 7 to 10% (W/W)
Lavandulae aetheroleum per full bath at 35-38°C during 10-20 minutes.
A bath additive with 5% Lavandulae aetheroleum has been on the market in Austria since 1994. The
posology is the same as for the preparations in Germany.
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 9/45
2.3.
Specified strength/posology/route of administration/duration of use
for relevant preparations and indications
According to the ESCOP monograph (2009)
Indications
Mood disturbances such as restlessness, agitation or insomnia
Posology
- Lavender flower
An infusion is made of 1-2 teaspoons (approximately 0.8 to 1.6 g) in 150 ml of water. The number of
doses is not specified.
Tincture (1:5 in 50% v/v ethanol), 60 drops per day
- Lavender oil
1-4 drops (approximately 20-80 mg) e.g. on a sugar cube
According to Blumenthal (2000) (referring to Commission E monographs)
Indications
Internal use: restlessness or insomnia and nervous stomach irritation, Roehmheld’s syndrome
(stomach discomfort), meteorism and nervous intestinal discomfort
For balneotherapy: treatment of functional circulatory disorders.
The German standard license for lavender tea lists it for restlessness, sleeplessness, lack of appetite,
nervous irritable stomach, meteorism and nervous disorders of the intestines.
Posology
Infusion: 1-2 teaspoons (approximately 0.8-1.6 g) in 150 ml water
Essential oil: 1-4 drops (approximately 20-80 mg) e.g. on a sugar cube
Bath additive: 20-100 g dried flowers for a 20 liter bath
According to the British Herbal Pharmacopoeia (1979 and the 1983 compilation)
Posology
Internally as a tea: dried flowers 1-2 g by infusion 3 times daily
Tincture (1:5) in 60% ethanol, 2-4 ml 3 times daily
Lavender oil B.P.C. (1973), 0.06–0.2 ml 3 times daily
According to Leclerc (1966)
Lavandulae flos is used in case of asthma, whooping cough, influenza and laryngitis.
An infusion is made of 5 parts per 100 (W/W) and 4 cups a day are prescribed.
According to Valnet (since 1964)
Indications
Internal use:
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 10/45
- Irritability, spasms, insomnia
- Fever blasts, infectious diseases
- Neurasthenia, melancholy
- Respiratory diseases: asthma, whooping cough, influenza, bronchitis due to whooping cough
- Oliguria
- Rhumatism
- Instability during childhood
- Atonic stomach or intestinal atony
- Migraine, vertigo, hysteria, sequellae of paralysia
- Typhoid enteritis (diarrhoea)
- Cystitis, blennorrhoea
- Dermal eruptions
- Intestinal parasites
- Metrorrhagia, leucorrhoea
- Hypertension
Posology
Infusion: 1 teaspoon in a cup of boiled water, infusion during 10 minutes: 3 cups per day between
meals.
Alcoholature: 40 drops 4 times daily in water (no detailed composition of alcoholature communicated).
Essential oil: 2-5 drops in honey or in an alcoholic solution. In case of anesthesia: 1 g aids at mentally
relaxing, without losing intellectual capacity.
Vaporisation: make a solution of 2% in water. To be vaporised in public rooms.
According to Madaus (1938)
Indications
Internal use:
Lavender mildly acts on the nervous system, especially in case of migraine. It is used against
neurasthenia, vertigo, nervous tachycardia, general nervous tension, hysteria, spasms, weakness and
sleeplessness.
Lavender has been used against affections of the stomach like gastritis, against meteorism and edema.
External use:
Lavender flowers are used as a bath additive.
Lavender oil is used for local massage in case of rheumatism, gout, neuralgia, ischias and scabies.
Rinsing fluid is made in case of
fluor albus
.
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 11/45
Posology
Essential oil: 8 drops (without further specification)
Tincture (strength not given): 10-15 drops
Infusion: 2-3 teaspoons (= 3-4.5 g) daily
3.
Non-Clinical Data
3.1.
Overview of available pharmacological data regarding the herbal
substance(s), herbal preparation(s) and relevant constituents thereof
In vitro
studies
Antimicrobial effects
Lavender oil had an antimicrobial activity against
Escherichia coli, Bacillus subtilis, Candida albicans
and
Staphylococcus aureus
, but not against
Pseudomonas aeruginosa
. The model used was the plate
diffusion test. No details about the concentrations used are mentioned. Linalool was active against
Streptococcus mutans
with a MIC of 1600 µg/ml which is a rather high concentration (Kubo et al.
1993).
Eight essential oils were examined using the agar dilution method, including
Carum carvi, Citrus
aurantium
var.
amara, Foeniculum vulgare dulce, Illicium verum, Lavandula angustifolia, Mentha
arvensis, Mentha x piperita,
and
Trachyspermum copticum
. Doubling dilutions of the essential oils were
tested against 12 species of intestinal bacteria, which represent the major genera found in the human
gastrointestinal tract (GIT).
Carum carvi, Lavandula angustifolia, Trachyspermum copticum,
and
Citrus
aurantium
var.
amara
essential oils displayed the greatest degree of selectivity, inhibiting the growth
of potential pathogens at concentrations that had no effect on the beneficial bacteria examined. The
most promising essential oils for the treatment of intestinal dysbiosis are
Carum carvi, Lavandula
angustifolia, Trachyspermum copticum,
and
Citrus aurantium
var.
amara
. The herbs from which these
oils are derived have long been used in the treatment of gastrointestinal symptoms and the
in vitro
results of this study suggest that their ingestion will have little detrimental impact on beneficial
members of the GIT microflora. More research is needed, however, to investigate tolerability and
safety concerns, and verify the selective action of these agents (Hawrelak et al. 2009).
Spasmolytic effects
The ileum of the guinea-pig and the rat uterus and phrenic nerve diaphragm were used as an
experimental model. These isolated organs contract when exposed to acetylcholine, histamine or
noradrenaline or electrically stimulated (field stimulation). Lavender oil inhibited the contractions of the
isolated ileum by about 50%. Pure linalool had similar effects. In contrast with lavender oil, a
concentration-effect relationship was studied with linalool: 5x10
-5
to 2x10
-4
g/ml on the diaphragm and
4x10
-6
to 8x10
-5
g/ml was used on the isolated ileum; both organs were electrically stimulated.
However no concentration-effect curves were displayed.
The inhibition of the electrically stimulated contractions by lavender of guinea-pig ileum appeared to be
postsynaptic and not atropine-like, as lavender inhibited the contractile responses due to acetylcholine
and to histamine to a similar degree. The relaxation effect by isoprenaline was potentiated by linalool,
which may indicate a phosphodiesterase inhibitory activity (Lis-Balchin & Hart 1997 and 1999).
Experiments were designed to investigate the relaxation mechanism of linalyl acetate as the major
ingredient of lavender essential oil in rabbit carotid artery specimens. Linalyl acetate produced
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 12/45
sustained and progressive relaxation during the contraction caused by phenylephrine. The relaxation
effect of linalyl acetate at a concentration near the EC
50
was partially but significantly attenuated by
nitroarginine as an inhibitor of nitric oxide synthase, 1H-(1,2,4) oxadiazolo (4,3-a) quinoxaline-1-one
as an inhibitor of guanylyl cyclase, or by the denudation of endothelial cells. In specimens without
endothelium, the phenylephrine-induced contraction and phosphorylation of myosin light chain (MLC)
were significantly attenuated after the pretreatment with linalyl acetate. The relaxation caused by
linalyl acetate in the endothelium-denuded specimens was clearly inhibited by calyculin A as an
inhibitor of MLC phosphatase, although not by ML-9 as an inhibitor of MLC kinase. Furthermore,
suppression of the phenylephrine-induced contraction and MLC phosphorylation with linalyl acetate was
canceled by the pretreatment with calyculin A. These results suggest that linalyl acetate relaxes the
vascular smooth muscle through partial activation of the nitric oxide/cyclic guanosine monophosphate
pathway, and partial MLC dephosphorylation via activating MLC phosphatase (Koto et al. 2006).
Other effects
Cultures of cerebellar granular cells from rat pups were exposed to neurotoxic concentrates of
glutamate (10
-7
M). The neuroprotective effect of a dry aqueous extract from lavender flower (DER
approximately 5:1) was tested at concentrations of 10 µg/ml, 100 µg/ml, 1 mg/ml and 10 mg/ml. At
100 µg/ml and 1 mg/ml, the extract significantly reduced glutamate-induced neurotoxicity from 37%
to 29% (p<0.05) and 21% (p<0.001) respectively (Büyükokuroglu et al. 2003).
A study on MCF-7 human breast-cancer cells (positive for oestrogen receptors) demonstrated that
lavender oil is weakly oestrogenic in concentrations of 0.01 and 0.03 vol/vol%., treated for 18 hours.
In MDA-kb2 cells (positive for androgen receptors) lavender oil was revealed to be weakly anti-
androgenic in concentrations between 0.0001 and 0.01 vol/vol% treated for 24 hours (Henley et al.
2007).
Lavender oil concentration-dependently inhibited histamine release from peritoneal mast cells
(p< 0.05):
- stimulated by compound 48/80 (a synthetic phosphodiesterase and ATP-ase inhibitor) at dilutions of
1:500, 1:100, 1:10, 1:1 and undiluted
- stimulated by anti-dinitrophenyl IgE at dilutions of 1:100, 1:10, 1:1 and undiluted.
It also had a significant inhibitory effect on anti-dinitrophenyl IgE-induced TNF
α
secretion from
peritoneal mast cells at 1:1000, 1:100, 1:10 and undiluted (p< 0.05) (Kim & Cho, 1999).
Assessor’s comments:
the relevance of antimicrobial, spasmolytic as well as other effects is difficult
to evaluate, as no detailed information about concentrations as such and concentration-effect
relationship is available.
In vivo
studies
Anticonvulsive effects
Purpose
Species
Intervention
Outcome
To study the
anticonvulsive
effects of
lavender.
Female and
male rats.
Electroshock- and metrazole-
induced convulsions.
Electroshock-induced
convulsions were inhibited after
single intraperitoneal doses of
lavender oil at 138 and 140
mg/kg body weight respectively;
Metrazole-induced convulsions
were also inhibited in 60-70% of
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 13/45
Purpose
Species
Intervention
Outcome
the animals by intraperitoneal
doses of 200-300 mg/kg
(Atassanova-Shopova
&Roussinov 1970).
To study the
anticonvulsive
effects of
lavender.
Male mice
stimulated
with
pentetrazol,
nicotine or
strychnine
(groups of 3
to 7 mice per
convulsive
agent).
The anticonvulsive effects of
lavender oil inhalation (0.3, 0.5
and 1 ml of lavender oil soaked in
cotton, in a glass cylinder) were
studied in mice. Convulsions were
induced by pentetrazol (50 and
100 mg/kg i,p,), nicotine (7.5
mg/kg i.p,), strychnine (2.5
mg/kg i.p,) or by electroshocks
(80V, 0,4 seconds). The
convulsive agents or
electroshocks were administered
after inhalation of lavender oil for
15 minutes.
Compared to controls, lavender
oil blocked convulsions induced
by the lower dose of pentetrazol
and by nicotine. No
anticonvulsive effects were
observed with strychnine. After
electroshocks lavender oil dose-
dependently reduced tonic
extensions and clonic
convulsions (Yamada et al.
1994).
Sedative effects
Purpose
Species
Intervention
Outcomes
To study the
sleep
prolongation.
Rats.
Lavender oil administered IP to
rats at 100 mg/kg, anesthetized
with hexobarbital sodium (100
mg/kg IP) and alcohol (35%, 3.5
g/kg IP).
The duration of anaesthesia
induced by hexobarbital sodium
was doubled and anaesthesia
induced by alcohol (35%, 3.5
g/kg IP) was prolonged almost
two-fold. The duration of the
anesthesia by chloral hydrate
(300 mg/kg IP) was more than
1.5-fold longer (Atassanova-
Shopova & Roussinov 1970).
To study
locomotor
activity.
Male albino
mice.
Lavender oil IP administered
during the rotarod motor test.
Lavender oil administered IP at
200-300 mg/kg reduced
spontaneous locomotor activity,
as well as locomotor activity
increased by caffeine-sodium
benzoate or amphetamine; in
the rotarod test motor
coordination was reduced with
an ED
50
of 248 mg/kg
(Atassanova-Shopova &
Roussinov 1970).
To study
locomotor
6-month old
female mice.
Exposure to an atmosphere
containing the vapour of lavender
Locomotor activity decreased
remarkably and time-
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 14/45
Purpose
Species
Intervention
Outcomes
activity.
oil or its constituents linalool and
linalyl acetate.
dependently in two studies, after
60 minutes of inhalation,
motility was reduced by 43%
and 78% with lavender oil, 15%
and 73% with linalool, and 35%
and 69% with linalyl acetate as
compared to controls
(Buchbauer et al. 1991;
Buchbauer et al. 1993a). An
increase in activity of 160%
after an injection of caffeine
(0.1%, 0.5 ml IP) was reduced
to 105%, 126% and 132%
respectively by inhalation of the
vapour of lavender oil, linalool or
linalyl acetate (Buchbauer et al.
1991).
To study
stress-induced
hyperthermia.
Male Wistar
rats. A
transmitter
was implanted
in order to
make records
of heart rate
and body
temperature.
Cages with a bedding that had
been sprayed with 200 µl of a
0.03% solution of lavender oil,
green leaf odour (mixture of
hexenol and hexenal),
α
-pinene
or the solvent only (triethyl
citrate) as control (n=12 per
group, except for the control:
n=6).
Following transfer to this novel
environment the body
temperature of the rats
increased by almost 1°C,
indicating stress-induced
hyperthermia. This was
attenuated by green leaf odour
and
α
-pinene, but not by
lavender oil or solvent (Akutsu
et al. 2002).
To study
explorative
behaviour and
sleeping time.
Mice.
The four plates test with oral
administration of lavender oil at
0.4 ml/kg body weight (as a 1:60
dilution in olive oil) daily for 5
days.
Pentobarbital-induced sleeping
time of 30 minutes.
The hole board test and the
labyrinth test.
Lavender oil increased in the
number of explorations by 68%,
indicating an anxiolytic effect.
With the same single dose
sleeping time was prolonged to
35-59 minutes (Delaveau et al.
1989).
In other studies, the same dose
of lavender oil did not decrease
motility in the hole board test
nor increase the number of
explorations in the four plates
test or number of entries into
open arms in the labyrinth test
to statistically significant levels
(in terms of anxiolytic effects),
although modest increases were
observed. Pentobarbital-induced
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 15/45
Purpose
Species
Intervention
Outcomes
sleep latency was significantly
shortened (p< 0.03) and
pentobarbital-induced sleeping
time was increased (p<0.05)
compared to a control group,
indicating a sedative effect
(Guillemain et al. 1989).
To study
locomotor
activity.
Mice.
Linalool administered to mice
subcutaneously at 25, 50, 75 and
100 mg/kg.
Spontaneous locomotor activity
increased by 95% (p<0.05 for
75 mg/kg) and 300% (p<0.0005
for 100 mg/kg) respectively,
whereas 25 mg/kg produced a
nonsignificant increase of 15%,
and 50 mg/kg a nonsignificant
decrease of 34% (Peana et al.
2003).
To investigate
the effects of
lavender
essential oil
inhalation on
gerbil
behaviour.
Male and
female
gerbils.
Gerbil behaviour in the elevated
plus maze test was observed and
results compared with the effects
of diazepam (1 mg/kg) i.p. after
30 min and 2-week
administration. Odour exposure
was via an electronic vapouriser
and aroma stone, placed into the
animal holding room and the
experimental suite, but out of
reach of the animals, during
behavioural testing. Lavender oil
was refreshed 3 times daily with
4 drops of the essential oil, to
achieve the concentration
commonly recommended by
aromatherapists.
Traditional measures of open
entries showed an increasing
trend over the 2 weeks
exposure, whereas ethological
measures indicative of anxiety
(stretch-attend frequency and
percentage protected head-dips)
were significantly lower.
Exploratory behaviour and total
head-dip frequency started to
increase 24 h after lavender and
lasted for the 2 weeks exposure.
These results are comparable
with diazepam administration.
Females showed a significant
decrease in protected head-dips
compared to both males and to
female controls.
In conclusion, exposure to
lavender oil may have an
anxiolytic profile in gerbils
similar to that of the anxiolytic
diazepam (Bradley et al. 2007).
To study the
anticonflict
effects of
lavender oil
and identify
its active
ICR mice
Two conflict tests in ICR mice
were used and then the active
constituents were identified.
Lavender oil produced significant
anticonflict effects at 800 and
1600 mg/kg in the Geller conflict
Cineol, terpinen-4-ol, alpha-
pinene and beta-myrcene did
not produce any significant
anticonflict effects in the Geller
test. Linalyl acetate did not
produce any significant
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 16/45
Purpose
Species
Intervention
Outcomes
constituents.
test and at 800 mg/kg in the
Vogel conflict test, suggesting
that the oil has an anti-anxiety
effect. Analysis using GC/MS
revealed that lavender oil
contains 26 constituents, among
which alpha-pinene (ratio,
0.22%), camphene (0.06%),
beta-myrcene (5.33%), p-
cymene (0.3%), limonene
(1.06%), cineol (0.51%), linalool
(26.12%), borneol (1.21%),
terpinen-4-ol (4.64%), linalyl
acetate (26.32%), geranyl
acetate (2.14%) and
caryophyllene (7.55%) were
identified. We examined the
effects of linalool, linalyl acetate,
borneol, camphene, cineol,
terpinen-4-ol, alpha-pinene and
beta-myrcene using the Geller
and Vogel conflict tests in ICR
mice.
anticonflict effects in either test.
Both borneol and camphene at
800 mg/kg produced significant
anticonflict effects in the Geller,
but not in the Vogel conflict test.
Linalool, a major constituent of
lavender oil, produced significant
anticonflict effects at 600 and
400 mg/kg in the Geller and
Vogel tests, respectively,
findings that were similar to
those of lavender oil. Thus,
authors concluded that linalool is
the major pharmacologically
active constituent involved in
the anti-anxiety effect of
lavender oil (Umezu et al.
2006).
To establish a
valid animal
model of the
effects of
olfactory
stimuli on
anxiety, a
series of
experiments
was
conducted
using rats in
an open- field
test.
Rats.
Throughout, effects of lavender
oil were compared with the
effects of chlordiazepoxide (CDP),
as a reference anxiolytic with
well-known effects on open-field
behaviour. Rats were exposed to
lavender oil (0.1-1.0 ml) for 30
min (Experiment 1) or 1 h
(Experiment 2) prior to open-
field test and in the open field or
injected with CDP (10 mg/kg
i.p.). In Experiments 3 and 4,
various combinations of pre-
exposure times and amounts of
lavender oil were used.
CDP had predicted effects on
behaviour, and the higher doses
of lavender oil had some effects
on behaviour similar to those of
CDP. With sufficient exposure
time and quantity of lavender
the same effects were obtained
as in Experiment 2. Experiment
4 demonstrated that these
behavioural effects of lavender
could be obtained following pre-
exposure, even if no oil was
present in the open-field test. In
Experiments 2-4, lavender oil
increased immobility. Together,
these experiments suggest that
lavender oil does have anxiolytic
effects in the open field, but that
a sedative effect can also occur
at the highest doses (Shaw et al.
2007).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 17/45
Anti-inflammatory and analgesic effects
Purpose
Species
Intervention
Outcome
To study local
anti-
inflammatory
activity.
Mice and rats.
Ear swelling induced by the
standard compound 48/80 (200
µg/ear intradermally). Pre-
treatment with lavender oil
(mice).
Passive cutaneous anaphylaxis
induced by anti-dinitrophenyl IgE
(rats) and topical or intradermal
lavender oil.
Swelling (ear - mice) was
concentration-dependently
inhibited by topical or
intradermal pre-treatment with
lavender oil at concentrations of
1:100, 1:10, 1:1 and undiluted
(p<0.05).
Cutaneous anaphylaxis was also
concentration-dependently
inhibited following application of
lavender oil topically (1:100
non-significant; 1:10; 1:1 and
undiluted, p<0.05) or
intradermally (1:100,1:10 and
1:1 non-significant; undiluted,
p<0.05) (Kim & Cho 1999).
To study local
anti-
inflammatory
activity.
Mice
Linalool locally applied 30 minutes
before the 12-O-
tetradecanoylphorbol-13-acetate
(TPA)-induced mouse ear oedema
test.
2 mg of linalool inhibited
oedema by 30% (p<0.01)
(Yasukawa et al. 1989).
To study
systemic anti-
inflammatory
activity.
Male Wistar
rats.
Linalool administered by gavage
at 100 and 200 mg/kg three
hours before injection of
carrageenan (2.5 mg/kg body
weight) in the carrageenan-
induced paw-oedema test.
Oedema was inhibited by 23 and
24% respectively (Pulla Reddy &
Lokesh, 1994).
To study
systemic anti-
inflammatory
activity.
Rats.
The carrageenan-induced rat paw
oedema test. Linalool and linalyl
acetate perorally administered.
After 3 hours:
(-)-linalool at 25, 50 and 75
mg/kg body weight inhibited
oedema by 28, 29 and 33%
respectively (p<0.0l, p<0.01
and p<0.005);
(±)-linalool at 50 and 75
mg/kg (but not at 25
mg/kg) inhibited oedema by
51 and 38% (p<0.05 and
p<0.05);
linalyl acetate at 64 and 96
mg/kg (but not at 32
mg/kg) inhibited oedema by
40 and 36% (p<0.01 and
p<0.05).
H-linalool is the naturally-
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 18/45
Purpose
Species
Intervention
Outcome
occurring isomer, but the
racemate (±)-linalool may be
present in distilled or extracted
essential oil (Peana et al. 2002).
To study the
anti
nociceptive
effect.
Mice.
The acetic acid induced writhing
test or the hot plate test.
In the writhing test, linalool
inhibited the response dose-
dependently by 38% at 25
mg/kg subcutaneously (p=0.03)
and by 52% at 50 mg/kg
(p=0.01) and 47% at 75 mg/kg
(p=0.03). The effect of linalool
at 50 mg/kg was completely
reversed by IP-administered
naloxone (5 mg/kg) or atropine
(5 mg/kg).
In the hot plate test, linalool at
100 mg/kg significantly
increased reaction time, by 45%
after 2 hours (p=0.004) and by
89% after 3 hours (p=0.0001),
while lower doses had no effect
(Peana et al. 2003).
Linalool was subcutaneously
injected.
To study the
anti
nociceptive
effect.
Male Wistar
rats.
In the paw withdrawal test,
unilateral subplantar injection of
carrageenan and L-glutamate
induced a hyperalgesic effect
(decrease of thermal threshold)
on the injection side, while
prostaglandin E, induced
hyperalgesia on both the injection
and the contralateral side.
In the first test, linalool (50, 100
or 150 mg/kg) significantly
reduced withdrawal latencies
induced by carrageenan (p<0.05
to p<0.001), with no effect on
the contralateral paw.
Linalool at the highest dose (200
mg/kg intraplantar) prevented
the reduction in paw withdrawal
latency induced by L-glutamate
(p<0.0005), demonstrating anti
hyperalgesic and anti
nociceptive effects; an anti
nociceptive effect was also
apparent in the contralateral
paw (p=0.02) compared to the
untreated control.
In the test with prostaglandin E,
linalool at 200 mg/kg
antagonized paw withdrawal
latency on the side contralateral
to the prostaglandin E2 injection
(p=0.032), but inhibition of
withdrawal latencies on the side
Linalool was administered by
abdominal subcutaneous injection
30 minutes before intraplantar
injection of the hyperalgesic
substances.
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 19/45
Purpose
Species
Intervention
Outcome
of the injection were non-
significant (Peana et al. 2004a).
To study the
anti
nociceptive
effect.
Male mice and
Wistar rats.
The hot plate test with linalool
administered subcutaneously.
Linalool significantly increased
reaction time in the hot plate
test with mice (p=0.005 at 100
mg/kg and p=0.003 at 150
mg/kg).
Linalool at 50 and 100 mg/kg
s.c. caused a significant
reduction in responses (- 42%,
p =0.013 and -37%, p=0.04
respectively) in the early acute
phase of the formalin test, but
not in the late tonic phase
(rats). The highest dose (150
mg/kg) caused a significant anti
nociceptive effect in both phases
(early phase: 35%, p=0.048;
late phase: 32%, p=0.0038).
The antinociceptive effects of
linalool were reduced by pre-
treatment with atropine,
naloxone, sulpiride and
glibenclamide, but not by
pirenzepine or SCH-23390 (a
dopamine D1 receptor
antagonist) (Peana et al.
2004b).
The formalin test.
To study local
anaesthetic
effects.
Male New
Zealand
rabbits.
The rabbit conjunctival reflex test
with lavender oil, linalool and
linalyl acetate applied to the
conjunctival sac.
Local anaesthetic effects of
lavender oil, linalool and linalyl
acetate were demonstrated: 30-
2500 µg/ml dose-dependently
increased the number of stimuli
necessary to provoke the reflex
(p<0.01) (Ghelardini et al.
1999).
Enzyme-inducing effects
Purpose
Species
Intervention
Outcome
To study the
influence on
the enzyme
content.
Male Wistar
albino rats.
Enzyme activity after oral
administration of linalool.
Linalool administered at 1.5 g/kg
body weight for 5 days caused
induction of peroxisomal
bifunctional enzyme (2445 ng
control protein/µg protein loaded
vs. 1069 ng for controls;
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 20/45
Purpose
Species
Intervention
Outcome
p<0.001) but not of cytochrome
P450 IVA1 (1.76%
of total P450
vs. 2.43% for controls; non-
significant) (Roffey et al. 1990).
To study the
influence on
liver enzyme
content.
Wistar rats (4
week old).
Linalool (500 mg/kg) as a
solution in propylene glycol was
administered by gavage for 64
days.
Liver weight and relative liver
weight were unaffected by
linalool (500 mg/kg) up to day
30, but by day 64 there were
slight but significant increases in
these parameters compared to
controls (p<0.05). Microsomal
protein concentration was
unaffected up to day 14, but had
increased by 20%, by day 30
(p<0.02) and remained elevated
up to day 64. Cytochrome P450
and cytochrome b
concentrations showed a
biphasic response, both being
depressed on day 7 (p<0.022 in
each case) but subsequently
increased by 50% on day 30
(p<0.01). Cytochrome P450
remained at this level, whereas
cytochrome b, increased further
to 70% on day 64 (p<0.002)
(Parke et al. 1974).
Other effects
Purpose
Species
Intervention
Outcome
To study the
diuretic effect
of lavender
flower.
Female Wistar
rats.
An infusion of lavender flower (40
g/litre) was intragastrically
administered.
The infusion exerted significant
diuretic effects (p<0.01) in rats
70 and 99 minutes after
intragastric administration of
0.03 g/kg body weight. At
maximum diuretic response,
urinary osmolarity (111
mosmol/kg) was significantly
less (p<0.01) than that of the
untreated control (195
mosmol/kg) and of the positive
control, diosmin (162
mosmol/kg). Sodium excretion
was moderate (Elhajili et al.
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 21/45
Purpose
Species
Intervention
Outcome
2001).
3.2.
Overview of available pharmacokinetic data regarding the herbal
substance(s), herbal preparation(s) and relevant constituents thereof
Species
Intervention
Outcome
Mice.
Exposure of mice to a lavender oil
atmosphere.
A time-dependent increase in linalool plasma
levels (approximately 0.9 ng/ml after 30
minutes, 2.7 ng/ml after 60 minutes and 2.9
ng/ml after 90 minutes) (Buchbauer et al.
1993).
Mice.
A 1 hour exposure to a medium
containing the vapour of lavender oil
(37.3% linalool and 41.6% linalyl
acetate), linalool or linalyl acetate at
5 mg/liter.
Serum levels were 3 ng/ml for linalool and 11
ng/ml for linalyl acetate. After 1 hour of
exposure to linalool, the serum level was 8
g/ml, and after 1 hour of exposure to linalyl
acetate the level was 1 ng/ml and the serum
linalool level 4 ng/ml (Buchbauer et al. 1993;
Jirovetz et al. 1990; Bickers et al. 2003).
Rats.
Oral administration of labelled linalool
to rats at 500 mg/kg body weight.
After oral administration of labelled linalool
55% was excreted in the urine as the
glucuronic acid conjugate, while 23% was
excreted in expired air and 15% in the faeces
within 72 hours; only 3% was detected in the
tissues (Bickers et al. 2003).
3.3.
Overview of available toxicological data regarding the herbal
substance(s)/herbal preparation(s) and constituents thereof
Acute toxicity
The acute oral LD
50
of lavender oil in rats was found to be > 5 g/kg body weight.
Other authors reported the oral LD
50
in male rats as 6.2 ml/kg and in female rats as 5.0 ml/kg; the oral
LD
50
in male rats as 5 ml/kg and in female rats as 3 ml/kg.
Furthermore an oral LD
100
in male rats as > 7 ml/kg and in female rats as > 6 ml/kg was reported. In
an earlier study the acute oral LD
50
of lavender oil was determined as 9 g/kg (Buchbauer et al. 1991;
Delaveau et al. 1989; von Skramlik 1959).
Acute oral LD
50
values in rodents have been reported as 2.2-3.9 g/kg body weight for linalool and 5.0-
48.8 g/kg for linalyl esters. The dermal LD
50
of linalool in rabbits exceeded 5 g/kg. No adverse effects
were reported from administration of linalool to female mice via a stomach tube at 94, 188 or 375
mg/kg/day for 5 days (Bickers et al. 2003).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 22/45
Subacute toxicity
In a 90-day chronic dermal toxicity study in rats (20 per group), linalool was applied daily at 250, 1000
and 4000 mg/kg body weight. At 250 mg/kg no changes were observed except decreased activity and
transient erythema; at 1000 mg/kg weight gain and activity were reduced; at the highest dose level,
11 animals died (Bickers et al. 2003).
In a 90-day study, a 1:1 mixture of linalool and citronellol was added to the diet of rats to provide an
intake of about 50 mg/kg/day of each substance. A slight retardation of body weight gain was
observed in the males, but no effects were evident from histopathology, haematology, clinical
chemistry or urine analysis at weeks 6 and 12 (Bickers et al. 2003).
Investigations on rats showed that the acute toxicity of essential oil of lavender (OL), given p.o. in
olive oil, was relatively low, while when given to mice pharmacological tests demonstrated that it had
anxiolytic effects and prolonged sleep induced by i.p. pentobarbital Na (PB, Sanofi), though the latter
effect was reduced after repeated p.o. administration. Impaired balance, piloerection and
hypersalivation sometimes occurred. The authors concluded that, if its chronic toxicity is also low, OL
might be used instead of more active anxiolytics or tranquilizers for minor conditions (Delaveau et al.
1989).
Undiluted lavender oil was not irritant when applied to the backs of hairless mice or pigs, but was
slightly irritant on intact or abraded rabbit skin under occlusion for 24 hours (Opdyke 1976).
Undiluted linalool caused slight to severe irritation to guinea pigs and rabbits when applied to open or
occluded skin; no irritation was observed at 10% dilution. Undiluted linalyl acetate caused slight to
severe irritation in guinea pigs and rabbits; at 5% dilution it was slightly irritating to rabbits (Bickers
2003).
Mutagenicity
Linalool and linalyl acetate showed no mutagenic potential in the Ames mutagenicity test, with or
without metabolic activation (Eder et al. 1980; Eder et al. 1982a; Eder et al. 1982b; Ishidate et al.
1984).
In the mouse lymphoma assay, no effects were seen with linalool in the absence of metabolic
activation at concentrations up to 300 µg/ml; weak positive effects were observed in the presence of
metabolic activation at doses of 200 µg/ml and above (Bickers et al. 2003).
Linalool did not induce chromosomal aberrations when incubated with Chinese hamster fibroblast cells
at concentrations up to 0.25 mg/ml (Ishidate et al. 1984) nor with Chinese hamster ovary cells at
concentrations up to approximately 300 µg/ml (Bickers et al. 2003).
No induction of unscheduled DNA synthesis in rat hepatocytes was evident at concentrations of linalool
up to 50 µg/ml or linalyl acetate up to 300 µg/ml (Bickers et al. 2003).
3.4.
Overall conclusions on non-clinical data
Most of the experiments were done with Lavandulae aetheroleum, the herbal preparation that is used
in clinical conditions. Lavender flowers were used for investigating a diuretic action.
Experimental pharmacological data point to an activity in the central nervous system: anticonvulsive
effects, sleep prolongation, locomotor activity, explorative or anticonflict behaviour and anxiety. Well
known inflammatory and nociceptive experimental models were used.
As far as these interventions are concerned, high doses of lavender oil were used to obtain
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 23/45
pharmacological effects. These doses mostly cannot be extrapolated to human conditions. On the other
hand, dose-response relationship could be demonstrated in some investigations.
The outcomes are mostly positive. This may be due to a publication bias. The effect on enzyme
induction by linalool is difficult to translate to metabolic consequences.
The experimental pharmacokinetic data are limited. Most probably, oil constituents are excreted by the
urine as glucuronic conjugates.
Toxicity of lavender oil is not a major concern. Some components like linalool and linalyl acetate are
not mutagenic. As the preparations as such have not been tested up to now for genotoxicity, a
Community list entry cannot be established for
Lavandula
.
4.
Clinical Data
4.1.
Clinical Pharmacology
4.1.1.
Overview of pharmacodynamic data regarding the herbal
substance(s)/preparation(s) including data on relevant constituents
Effects on the central nervous system and neuronal activity
Clinical
question
Patients
Intervention
Outcome
To what
extent can
lavender oil
influence
indicators for
mood status?
Healthy adults
(n=20).
Subjects were exposed to
lavender oil (10% in grape seed
oil, 3 drops on a cotton swab held
8 cm from the participant's nose
for 3 minutes).
As compared to baseline, beta
power in the EEG increased,
suggesting increased
drowsiness. Significantly lower
scores were obtained for
depressed mood (assessed by
the Profile of Mood States: -56%
p<0.01) and anxiety (assessed
bv the State Trait Anxiety
Inventorv: -9%, p<0.05). The
volunteers reported feeling more
relaxed (tense/relaxed and
drowsy/alert visual analogue
mood scales: + 25.9%,
p<0.001) and performed
mathematical computations
faster and more accurately (von
Skramlik 1959).
Further data analysis revealed
significant EEG shift (p<0.05)
with greater left frontal EEG
activation (associated with
extrovert behaviour and less
depressed mood) (Sanders et al.
2002).
What is the
24 healthy
The acute sedative effects of p.o. Diazepam, Valerian and
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 24/45
Clinical
question
Patients
Intervention
Outcome
possible
influence of
a.o. lavender
oil on the
EEG-pattern?
females.
extracts of
Valeriana officinalis,
Lavandula angustifolia, Passiflora
incarnata, Kava-kava, Melissa
officinalis, Eschscholzia
californica, Hypericum perforatum
and
Ginkgo biloba
(all Lichtwer)
were compared to those of
diazepam using quantitative EEG
recordings. Studies followed a
double-blind, randomized,
crossover design.
Lavandula
were sedative on a
self-rating of tiredness.
Diazepam increased power in
the beta frequency band of the
EEG and decreased power in the
alpha and sub-alpha bands.
Valerian increased power in the
delta, theta and alpha1 bands.
Lavandula
had a minimal effect
on power. Quantitative EEGs are
a sensitive means of describing
drug-induced CNS activity
changes, but do not constitute a
good screening method for
potential sedatives (Schulz et al.
1998).
How does
lavender oil
influence EEG-
patterns?
Healthy
female
volunteers
(n=13).
EEG recordings made during and
after inhalation of lavender oil for
90 seconds (diffuser fixed on the
chest; no details on concentration
given).
Alpha I frequencies (8-10 Hz) in
parietal and posterior temporal
regions significantly decreased
soon after the onset of
inhalation (p<0.01). This was
associated with a comfortable
feeling in the subjects (Masago
et al. 2000).
How does
lavender oil
influence EEG
and behaviour
of newborn
babies?
Newborn
babies
(n=20).
The effects were evaluated of
inhalation of lavender oil (10%
V/V in grape seed oil, 3 drops on
a cotton swab held 15 cm from
the nose for 2 minutes) on the
behaviour of 20 newborn babies.
Infants of depressed mothers
showed increased relative left
frontal EEG asymmetry from
baseline during the odour
exposure phase (p<0.01). In
contrast, infants of non-
depressed mothers showed no
change in frontal EEG-
asymmetry from baseline during
the odour exposure phase.
Among the behaviours recorded
(negative affect, head turns, lip
licking, and nose wrinkling), the
only differences were that
infants of depressed mothers
showed increased head turning
during exposure to the odour
(p<0.05) (Fernandez et al.
2004).
To what
extent does
Healthy
women
In a randomized single-blind
study, the effect of a lavender oil
"Positive" effects of bathing -
irrespective of whether or not
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 25/45
Clinical
question
Patients
Intervention
Outcome
lavender oil
influence
mood and
positive
behaviour
towards future
events?
(n=40).
bath (3 ml/bath) on psychological
well-being was evaluated. The
participants, randomly assigned
to use either grape seed oil or
20% lavender oil in grape seed oil
in their bath for 14 days,
assessed their well-being with the
Mood Adjective Checklist of the
University of Wales Institute of
Science and Technology.
lavender oil was added to the
bath - were evident with respect
to energetic arousal, tense
arousal and hedonic tone, while
anger-frustration was selectively
reduced by lavender oil.
In the further study using the
Macleod and Byrne Future
Events procedure, no effect was
observed on the rate of positive
responses to possible future
events but negative responses
were reduced after lavender oil
baths (Morris 2002).
In a further study a similar design
and assessment by the Macleod
and Byrne Future Events
procedure was done.
To what
extent does
lavender oil
influence
cognitive
functions?
Healthy
volunteers
(n=144).
Participants were assigned to one
of three independent groups and
subsequently performed the
Cognitive Drug Research
computerized cognitive
assessment battery in a cubicle
containing the odour of lavender
oil or rosemary oil (from 4 drops
on a diffuser pad, placed under a
bench in the testing cubicles) or
no odour (as a control). Visual
analogue mood questionnaires
were completed prior to exposure
to the odour and after completion
of the test battery.
Compared to controls, lavender
odour caused significant
impairment in performance of
working memory (p<0.05) and
impaired reaction times for both
memory and attention based
tasks (working memory
subfactor, speed of memory
factor, speed of attention factor,
alertness and contentedness)
(Moss et al. 2003).
What
influence has
lavender oil
on arousal
and mental
stress?
Healthy
volunteers
(n=42).
The effect of lavender oil (from a
diffuser on the floor of the
experimental room for 20
minutes) was assessed by a
Japanese version of Cox and
Mackay's stress/arousal adjective
checklist in three groups of
healthy volunteers. Stress was
induced by waiting in a
soundproofed small room for 20
minutes. One group of 14 was
placed in the room without
exposure to the oil, a group of 15
was exposed to lavender oil, and
a group of 13 did not have to wait
Analysis suggested that lavender
odour was associated with
reduced mental stress and
increased arousal rate (p<0.01)
(Motomura et al. 2001).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 26/45
Clinical
question
Patients
Intervention
Outcome
in the soundproofed room.
To what
extent does
lavender oil
influence pain
sensation?
Healthy
volunteers
(13 men and
13 women).
The effects of inhalation of
lavender oil (5 drops on cotton
gauze placed 30 cm below the
nose for 10 minutes), rosemary
oil or water (as a control) on
sensory and affective responses
to experimentally-induced pain
were studied in 13 men and 13
women in a randomized cross-
over design. Pre- and post-
treatment scores were
documented for quantitative
sensory ratings of contact heat
pain (thermode placed on the
forearm), pressure pain (pressure
algometer applied to the
trapezius and masseter) and
ischaemic pain (submaximal
effort tourniquet procedure:
elevating the arm above heart
level for 30 seconds, occlusion of
circulation with a standard blood
pressure cuff, hand-grip exercises
with lowered arm). Subjective
ratings of treatment-related
changes in pain intensity and pain
unpleasantness were obtained for
each condition using a visual
analogue scale.
Quantitative pain sensitivity
ratings were unchanged in both
groups. Retrospectively,
however, subjective ratings of
both perceived pain intensity
and perceived pain
unpleasantness were
significantly less after treatment
with lavender (p<0.01) (Gedney
et al. 2004).
What is the
influence of
lavender on
sustained
attention?
Healthy
volunteers
(n=7; aged
20-24 years).
Exposure to volatile oil vapours,
an odour delivery system passed
air at a standard rate through
sample bottles and presented, in
randomized order, dispersions of
lavender oil (0.29 mg per liter of
air), eucalyptus oil (4.8 mg per
liter of air) and a no-odour control
to a point exactly 10 cm below
the nose.
During 30-minute vigilance
tasks, involving selection
responses in relation to numbers
changing every second on a
computer screen, the gradual
increase in reaction time was
found to be significantly lower
with lavender oil odour than with
the control (p<0.001).
The results suggested that the
odour of lavender oil helped to
maintain sustained attention
during the long-term task
(Shimizu et al. 2008).
What is the
Healthy
Aromatherapy given to subjects
The State Anxiety scores
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 27/45
Clinical
question
Patients
Intervention
Outcome
influence of
lavender on
EEG activity,
alertness and
mood?
volunteers
(n=40; mean
age 31y).
seated in a special massage chair.
Lavender or rosemary oil (3
drops) diluted with a 10%
concentration in grape seed oil
were placed on a dental swab and
presented in a 100 ml plastic vial
which the subjects held about 3
inches from their nose for a
period of 3 minutes.
decreased in both groups
(p<0.05);
Only the lavender group had
a significantly better mood
on the POMS (= Profile Of
Mood States) (p< 0.01);
Both groups felt more
relaxed (p< 0.001);
The accuracy scores
improved significantly
(p< 0.05).
Frontal alpha power
increased after lavender,
suggesting increased
drowsiness (Diego et al.
1998).
What is the
influence of
lavender oil
on
neuropsychic
activity?
Healthy
medical
students
(n=48; 22-23
y), subdivided
in groups of
16 subjects,
receiving
lavender, rose
or geranium
oil.
Inhalation of lavender oil (50 ml
of a 1% solution nebulized in a
room of 176 m³). Assessment of
neuropsychic activity by the
Pauli-test (assessing
concentration, working efficiency,
reaction and attention).
The lavender oil stimulated
neuropsychic activity, but results
are difficult to interpret by
differentiation of parameters
(Tašev T et al. 1969).
To what
extent does
lavender oil
influence
reaction time?
Healthy
volunteers
(n=10).
Computer-based reaction-time
tests (parts of the Munich
Attention Test) were performed
while inhaling air or lavender oil
vapour in 6 daily sessions.
Increases in reaction time were
observed on days 4 and 6 when
the subjects performed the tests
while inhaling lavender oil
vapour (Buchbauer et al.
1993b).
Cardiovascular system
Clinical
question
Patients
Intervention
Outcome
It was
examined
whether the
power spectral
analysis of
heart rate
variability
Healthy young
women
(n=10; 23+/-
3 years)
Continuous electrocardiographic
(ECG) monitoring before and after
(10, 20, 30 minutes) a stimulus
with lavender oil. Lavender oil
was topically administered by a
commercially available plaster for
aroma therapy (‘Lavender girl’,
Increases in the
parasympathetic tone were
observed after the lavender oil
seen as increases in the HF
component and decreases in the
LF/HF. Additional measurement
with positron emission
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 28/45
Clinical
question
Patients
Intervention
Outcome
(HRV) could
detect
changes in
autonomic
tone following
a treatment
with
Lavandula
essential oil.
Teikoku Pharmaceuticals, Tokyo,
Japan). No information was given
on the dose. HRV was expressed
by three indices: low (0.04-0.15
Hz) and high (0.15-0.40 Hz)
frequency components (nLF and
nHF respectively) as well as LF/HF
ratio.
tomography (PET) demonstrated
the regional metabolic activation
in the orbitofrontal, posterior
cingulate gyrus, brainstem,
thalamus and cerebellum, as
well as the reductions in the
pre/post-central gyrus and
frontal eye field. These results
suggested that lavender
aromatic treatment induced not
only relaxation but also
increased arousal level in these
subjects (Duan et al. 2007).
To what
extent does
lavender oil
influence
blood flow and
nerve activity
when taken as
a footbath?
Healthy young
women
(n=10; 19-
21y).
In a randomized cross-over study
subjects took a hot footbath for
10 minutes with and without
lavender oil (2 ml to 4 liters of
water; 0.05%). Effects on the
autonomic nervous system were
recorded on an electrocardiogram
and by finger tip blood flow and
respiratory rate. Autonomic
function was evaluated using
spectral analysis of heart rate
variability.
A significant increase in finger
tip blood flow (34.8 to 40.1
ml/min/100g; no change without
lavender oil) was recorded.
Parasympathetic nerve activity
increased significantly (p<0.05)
during both types of footbath.
With lavender oil, delayed
changes in the balance of
autonomic activity were
observed, suggesting relaxation.
No changes were observed in
heart or respiratory rates (Saeki
2000).
To what
extent does
lavender oil
influence
cardiovascular
parameters
after exercise?
Healthy
volunteers
(n=20).
After performing moderate
physical exercise for 2 minutes,
subjects rested for 10 minutes.
During this time they were
randomly exposed to an
atmosphere with or without
lavender oil (10 drops in water,
nebulized).
Compared to the controls, the
volunteers exposed to lavender
oil had lower diastolic (- 6.1
mmHg) and systolic blood
pressure (- 15.1 mmHg), and
lower arterial pressure (- 8.5
mmHg) and heart rate (- 15
beats/minute), although the
differences were not statistically
significant (Romine et al. 1999).
Antioxidative activity
Clinical
question
Patients
Intervention
Outcome
How does the
smelling of
lavender and
22 healthy
volunteers.
They sniffed aroma for 5 min, and
each subject's saliva was
collected immediately. FRSA was
Various physiologically active
substances in saliva such as
cortisol, secretory IgA, and
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 29/45
Clinical
question
Patients
Intervention
Outcome
rosemary
essential oil
influence the
total salivary
FRSA (Free
Radical
Scavenging
Activity)?
measured using 1.1- diphenyl-2-
picrylhydrazyl.
alpha-amylase activity were
found to be correlated with
aroma-induced FRSA. The FRSA
values were increased by
stimulation with low
concentrations (1000 times
dilution) of lavender or by high-
concentrations (10 times
dilution) of rosemary. In
contrast, both lavender and
rosemary stimulations decreased
cortisol levels. A significant
inverse correlation was observed
between the FRSA values and
the cortisol levels with each
concentration of rosemary
stimulation. No significant
changes were noted in sIgA or
alpha-amylase. These findings
clarify that lavender and
rosemary enhance FRSA and
decrease the stress hormone,
cortisol, which protects the body
from oxidative stress. The body
possesses various antioxidative
systems (FRSA) for preventing
oxidative stress, and saliva
contains such activity (Atsumi &
Tonosaki 2007).
4.1.2.
Overview of pharmacokinetic data regarding the herbal
substance(s)/preparation(s) including data on relevant constituents
Patient
Intervention
Outcome
Male
volunteer.
A massage oil containing 2% of
lavender oil (approximately 25%
linalool and 30% linalyl acetate) was
gently massaged on to the abdomen
for 10 minutes.
Trace amounts of both linalool and linalyl
acetate were detected in the blood within 5
minutes of finishing the massage, and peak
plasma concentrations of 121 ng/ml for
linalool and 100 ng/ml for linalyl acetate were
reached after 19 minutes. Most of the linalool
and linalyl acetate disappeared from the blood
within 90 minutes, both having a biological
half-life of approximately 14 minutes (Jäger et
al. 1992).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 30/45
4.2.
Clinical Efficacy
4.2.1.
Dose response studies
Not applicable.
4.2.2.
Clinical studies (case studies and clinical trials)
Anxiety
Purpose
Patients
Intervention
Outcome
To evaluate
possible
anxiolytic
effects of
lavender oil.
Healthy
volunteers
(n=97; 57
females, 39
males; aged
between 18
and 74
years).
Participants
refrained from
alcohol, tea
and coffee 24
hours prior to
the study.
Orally administered lavender
capsules (placebo, 100, 200 µl)
were tested in a randomised
between-subjects double-blind
study. Film clips were used to
elicit anxiety. Measures included
anxiety, State Trait Anxiety
Inventory (STAI), mood, positive
and negative affect scale
(PANAS), heart rate (HR),
galvanic skin response (GSR),
and heart rate variation (HRV).
Following baseline
measurements, capsules were
administered. Participants viewed
a neutral film clip, then an
anxiety-provoking and light-
hearted recovery film clip.
For the 200 µl lavender dose
during the neutral film clip there
was a trend towards reduced
state anxiety, GSR and HR and
increased HRV. In the anxiety-
eliciting film, lavender was
mildly beneficial in females but
only on HRV measures. In males
sympathetic arousal increased
during the anxiety film (GSR).
HRV significantly increased at
200 µl during all three film clips
in females, suggesting
decreased anxiety. These
findings suggest that lavender
has anxiolytic effects in humans
under conditions of low anxiety,
but these effects may not
extend to conditions of high
anxiety (Bradley et al. 2009).
To investigate
the effect of
lavender oil in
general
anxiety
disorder
(GAD).
Patients
(n=77; 18 to
65 years) with
primary
diagnosis of
GAD
according to
the DSM-IV
criteria and
outpatient
treatment by
a general
practitioner
were selected.
In order to be
eligible for
study
inclusion, all
A double-blind, randomized,
double dummy, controlled clinical
study was performed to evaluate
the efficacy of silexan (80 mg
lavender oil), a new oral lavender
oil capsule preparation, versus a
benzodiazepine. In this study, the
efficacy of a 6-week intake of
silexan compared to lorazepam
(0.5 mg) was investigated in
adults with GAD. The primary
target variable was the change in
the Hamilton Anxiety Rating Scale
(HAM-A-total score) as an
objective measurement of the
severity of anxiety between
baseline and week 6.
The results suggest that silexan
effectively ameliorates
generalized anxiety comparable
to a common benzodiazepine
(lorazepam). The mean of the
HAM-A-total score (primary
parameter) decreased clearly
and to a similar extent in both
groups (by 11.3
+
6.7 points
(45%) in the silexan group and
by 11.6
+
6.6 points (46%) in
the lorazepam group, from 25
+
4 points at baseline in both
groups). During the active
treatment period, the two HAM-
A subscores "somatic anxiety"
(HAM-A subscore I) and "psychic
anxiety" (HAM-A subscore II)
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 31/45
Purpose
Patients
Intervention
Outcome
patients were
required to
have a
Hamilton
Anxiety
(HAM-A) total
score of
>
18
and item 1
‘anxious
mood’
>
2
and item 2
‘tension’
>
2.
also decreased clearly and to a
similar extent in both groups.
The changes in other subscores
measured during the study, such
as the SAS (Self-rating Anxiety
Scale), PSWQ-PW (Penn State
Worry Questionnaire), SF 36
Health survey Questionnaire and
Clinical Global Impressions of
severity of disorder (CGI item 1,
CGI item 2, CGI item 3), and the
results of the sleep diary
demonstrated comparable
positive effects of the two
compounds. The results
demonstrate that silexan is as
effective as lorazepam in adults
with GAD. The safety of silexan
was also demonstrated. Since
lavender oil showed no sedative
effects in the study and has no
potential for drug abuse, silexan
appears to be an effective and
well tolerated alternative to
benzodiazepines for amelioration
of generalised anxiety, according
to the authors (Woelk and
Schläfke 2010).
Before being
included,
patients
underwent a
one-week
screening
phase to
ensure wash-
out of any
other drugs.
Patients with
a decrease of
25% or more
of the HAM-A
total score
during this
phase were to
be excluded.
To review the
effect of
lavender scent
on
anticipatory
anxiety in
dental
consultations.
Dental
patients in
ambulatory
practice
(n=340).
In a cluster randomized-
controlled trial, patients' anxiety
was assessed while waiting for a
scheduled dental appointment,
either under the odour of
lavender or with no odour.
Current anxiety, assessed by the
brief State Trait Anxiety Indicator
(STAI-6), and generalized dental
anxiety, assessed by the Modified
Dental Anxiety Scale (MDAS)
were examined.
Analyses of variance (anovas)
showed that although both
groups showed similar,
moderate levels of generalized
dental anxiety (MDAS F=2.17,
p>0.05) the lavender group
reported significantly lower
current anxiety (STAI: F=74.69,
p<0.001) than the control
group. Although anxiety about
future dental visits seems to be
unaffected, lavender scent
reduces state anxiety in dental
patients (Kritsidima et al. 2010)
To investigate
the effects of
Korean elderly
women
A quasi-experimental, control
group, pretest-posttest design
The intervention produced
significant differences in the
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 32/45
Purpose
Patients
Intervention
Outcome
aromatherapy
massage on
the anxiety
and self-
esteem.
(n=36)
was used: 16 patients in the
experimental group and 20 in the
control group. Aromatherapy
massage using lavender,
chamomile, rosemary and lemon
was given to the experimental
group only. Each massage session
lasted 20 min, and was
performed 3 times per week for
two 3-week periods with an
intervening 1-week break.
anxiety and self-esteem and no
significant differences in blood
pressure or pulse rate between
the two groups. These results
suggest that aromatherapy
massage exerts positive effects
on anxiety and self-esteem.
More objective, clinical measures
should be applied in a future
study with a randomized
placebo-controlled design (Rho
et al. 2006).
The purpose
of this study
was to
evaluate the
use of
aromatherapy
to reduce
anxiety prior
to a scheduled
colonoscopy
or esophago
gastroduode
noscopy.
A controlled,
prospective
study was
done on a
convenience
sample of 118
patients
(mean age
52y, range
24-57y, 50%
male). There
was no
difference
between the
experimental
and control
group in
enjoyment of
scent
(p=0.94).
The state component of the State
Trait anxiety Inventory (STAI)
was used to evaluate patients'
anxiety levels pre- and post-
aromatherapy. The control group
was given inert oil (placebo) for
inhalation, and the experimental
group was given lavender oil for
inhalation.
The STAI state anxiety raw
score revealed that patients
were at the 99th (women) and
96th (men) percentiles for
anxiety. The intervention group
and the control group had
similar levels of state anxiety
prior to the beginning of the
study (p=0.64). There was no
difference in state anxiety levels
between pre-and post-placebo
inhalation in the control group
(p=0.63). There was no
statistical difference in state
anxiety levels between pre- and
post-lavender inhalation in the
experimental group (p=0.47).
Although this study did not show
aromatherapy to be effective
based on statistical analysis,
patients did generally report the
lavender scent to be pleasant.
Lavender is an inexpensive and
popular technique for relaxation
that can be offered to patients
as an opportunity to promote
preprocedural stress reduction in
a hospital setting (Muzzarelli et
al. 2006).
Depression
Clinical
question
Patients
Intervention
Outcome
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 33/45
Clinical
question
Patients
Intervention
Outcome
To what
extent does a
lavender
flower tincture
influence the
status of
depressed
patients as
compared to
imipramine?
Patients who
met the DSM
criteria for
major
depression
(based on the
structured
clinical
interview for
DSM IV) and
had a baseline
score of at
least 18 on
the Hamilton
Rating Scale
for
Depression
(HAM-D)
(n=45).
Patients were assigned to the
following daily oral treatments for
4 weeks:
Highly significant improvements
in HAM-D scores (p<0.0001)
were observed in groups A
(approximately 19 to 12) and B
(approximately 19 to 9),
although lavender tincture at
this dosage was less effective
than imipramine (p=0.0001). In
group C the combination of
lavender tincture and
imipramine was more effective
than imipramine alone
(approximately 19 to 5 versus
19 to 9; p<0.0001)
(Akhondzadeh et al. 2003).
Group A: lavender flower
tincture (60 drops/day) + a
placebo tablet;
Group B: an imipramine
tablet (100 mg/day) +
placebo drops;
Group C: lavender flower
tincture (60 drops/day) + 1
imipramine tablet (100
mg/day).
Analgesia
Purpose
Patients
Intervention
Outcome
To investigate
the analgesic
efficacy of
postoperative
lavender oil
aromatherapy
Patients
undergoing
breast biopsy
surgery
(n=50).
25 patients received
supplemental oxygen through a
face mask with two drops of 2%
lavender oil postoperatively. The
remainder of the patients
received supplemental oxygen
through a face mask with no
lavender oil. Outcome variables
included pain scores (a numeric
rating scale from 0 to 10) at 5,
30, and 60 minutes
postoperatively, narcotic
requirements in the
postanesthesia care unit (PACU),
patient satisfaction with pain
control, as well as time to
discharge from the PACU.
There were no significant
differences in narcotic
requirements and recovery room
discharge times between the two
groups. Postoperative lavender
oil aromatherapy did not
significantly affect pain scores.
However, patients in the
lavender group reported a
higher satisfaction rate with pain
control than patients in the
control group (p=0.0001)
(Kim
et al. 2006).
To assess the
efficacy of
acupressure
using lavender
oil.
Adults (32
patients
enrolled of
which 28
completed the
An add-on treatment for pain
relief and enhancing physical
functional activities. Experimental
study design: the Telehealth clinic
and the community centre, Hong
A panel 8 experts in the
musculoskeletal field verified the
content validity of the outcome
measures (inter-raters
reliability=0.98). The baseline
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 34/45
Purpose
Patients
Intervention
Outcome
study; mean
age 51.2y
+
7.6) with sub-
acute non-
specific neck
pain.
Kong. A course of 8-session
manual acupressure with
lavender oil over a 3 week period.
Changes from baseline to the end
of treatment were assessed on
neck pain intensity (by Visual
Analogue Scale (VAS)); stiffness
level; stress level; neck lateral
flexion, forward flexion and
extension in cm, and interference
with daily activities.
VAS score of neck pain intensity
(primary outcome) for the
intervention and control groups
were 5.12 and 4.91 out of 10,
respectively (p=0.72). One
month after the end of
treatment, compared to the
control group, the manual
acupressure group had 23%
reduced pain intensity (p=0.02),
23% reduced neck stiffness
(p=0.001), 39% reduced stress
level (p=0.0001), improved neck
flexion (p=0.02), neck lateral
flexion (p=0.02), and neck
extension (p=0.01). However,
improvements in functional
disability level were found in
both the manual acupressure
group (p=0.001) and control
group (p=0.02). Our results
show that eight sessions of
acupressure with aromatic
lavender oil were an effective
method for short-term neck pain
relief (Yip & Tse 2006).
Clinical
question
Patients
Intervention
Outcome
To what
extent does
lavender oil
improve low
back pain?
Adult patients
with sub-
acute or
chronic non-
specific low
back pain
(number that
completed the
study:
intervention
group=27;
control
group=24).
In a randomized controlled study,
the effect on pain relief and
enhancement of physical
functional activities of acupoint
stimulation with electrodes
combined with acupressure using
lavender oil (in addition to
conventional treatment) was
assessed. Over a 3-week period
the patients had 8 sessions of
relaxation acupoint stimulation,
each of 35-40 minutes, followed
by acupressure massage with 3%
lavender oil in grape seed oil
using light to medium finger
pressure on 8 fixed acupoints for
2 minutes each. Patients in the
Baseline VAS scores for the
intervention and control groups
were 6.38 and 5.70 respectively
(p=0.24). One week after the
end of treatment the
intervention group reported 39%
greater reduction in pain
intensity than the control group
(p=0.0001) and had improved
walking time (p=0.05) and
greater lateral spine flexibility
(p=0.01) (Yip & Tse 2004).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 35/45
Clinical
question
Patients
Intervention
Outcome
control group received
conventional treatment only.
Outcome measures were changes
in pain intensity scores (10 cm
VAS) and duration from baseline
to end of treatment, lateral
fingertip-to-ground distance,
walking time (to cover 15 meter)
and interference with daily
activities.
To what
extent can
lavender oil
alleviate
postoperative
pain?
Morbidly
obese
patients who
had
undergone
surgery for
laparoscopic
adjustable
gastric
banding
(n=54).
In a randomized, placebo
controlled study patients were
treated, upon arrival at the post-
anaesthesia care unit, by
application of either lavender oil
or non-scented baby oil to the
oxygen face mask. The two
groups were comparable with
regard to patient characteristics,
intra-operative drug use and
surgical time. Postoperative pain
was treated with morphine and
the level of pain was assessed at
5, 30 and 60 minutes from
numerical rating scores (0-1 0).
Patients in the lavender group
required significantly less
morphine postoperatively than
those in the placebo group: 2.38
mg vs 4.26 mg (p=0.04).
Furthermore, significantly more
patients in the placebo group
(22/27, 82%) than in the
lavender group (12/26, 46%)
required analgesics for
postoperative pain (p=0.007)
(Kim et al. 2007).
To what
extent does
lavender oil
influence pain
perception?
Patients with
vascular
wounds
requiring
frequent
painful
dressing
changes
(n=8).
In a pilot, the effects were
assessed of diffusion of 15-20
drops of lavender oil by means of
an aroma stream diffuser during
the dressing change (in addition
to conventional analgesics). Pain
perception was assessed by two
measures from the McGill Pain
Questionnaire, the Visual
Analogue Scale (VAS) and the
Present Pain Inventory; a Sleep
Questionnaire and the Spielberger
State Trait Anxiety Inventory
were also used. During five
dressing changes the patients
received, in random order, two
odor therapies (lavender or
lemon), music therapy of two
types, or no treatment.
Lavender oil diffusion did not
reduce pain intensity during
dressing changes, but at post-
dressing change assessments of
lavender therapy a significant
reduction in pain intensity was
evident from VAS scores
(p<0.05) (Kane et al. 2004).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 36/45
Sleeping disorders
Purpose
Patients
Intervention
Outcome
To test the
hypotheses
that Essential
Oil of
Lavender has
a sedative
effect and that
the resultant
sleep
promotes
therapeutic
activity.
Acutely ill
elderly people
and long-term
patients.
A pilot study was arranged,
followed by a more detailed trial
with long-term patients.
The results show a positive
trend towards improvement with
lavender (Hudson 1996).
To study the
hypnotic
effects of
lavender oil.
12 mid-life
women with
sleep
disturbances
(56y range
50-59y):
mean sleep
time 6.5
hours.
A cross-over placebo-controlled
study. Patients received a dose of
0.86 g (3 drops) lavender oil,
jasmine oil or base oil (placebo)
on their pillow on 3 separate
occasions (for 2 nights in a
balanced, placebo-controlled
cross-over design).
Lavandula angustifolia
oil was
mild hypnotic and jasmine oil a
stimulant. In contrast to jasmine
oil, lavender oil significantly
increased actual sleep time by a
mean of 69 minutes (p<0.05).
Perceived changes in self-rated
sedation and residual side-
effects did not reveal any
significant subjective
impairment. In comparison to
jasmine oil, ease of getting to
sleep and quality of sleep was
positively improved with the
lavender oil. Mean trends
indicated that in comparison to
jasmine, awakening was also
positively improved with
lavender oil, whilst jasmine
decreased sleep in contrast to
the placebo. Lavender oil may
be of value as a mild hypnotic
whilst jasmine, having an
opposite effect, may be helpful
in counteracting daytime
sleepiness (Austin & Alford
1997).
To explore the
effects of the
lavender
fragrance on
sleep and
depression in
42 women
college
students who
complained of
insomnia.
Patients were studied during a
four-week protocol (control
treatment week, 60% lavender
fragrance treatment week,
washout week, 100% lavender
fragrance treatment week). All
Among sleep variables, length of
time taken to fall asleep,
severity of insomnia, and self
satisfaction with sleep were
improved for the 60% (p<0.001,
p<0.001, p<0.001) and 100%
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 37/45
Purpose
Patients
Intervention
Outcome
women
college
students.
subjects were in the department
of nursing in a college and the
study was a single blind repeated
measurements experiment. For
the duration of the study, weekly
evaluations of sleep, patterns of
sleep disturbance, severity of
insomnia scale, self satisfaction
with sleep, and severity of
depression were performed.
(p<0.001, p<0.001, p<0.001)
week while the severity of
depression was improved only
for the 100% (p=0.002) week.
According to the study results, it
can be concluded that the
lavender fragrance had a
beneficial effect on insomnia and
depression in women college
students. Repeated studies are
needed to confirm effective
proportions of lavender oil and
carrier oil for insomnia and
depression (Lee & Lee 2006).
Malignant diseases
Clinical
question
Patients
Intervention
Outcome
To what
extent
lavender oil
could be
useful as an
adjuvant in
cancer
therapy?
The study
population
consisted of
17 still
conscious and
oriented in-
home hospice
patients. The
abstract of
the article
categorizes
them as
‘cancer’
patients
without
further
specification.
There are also
no details
given about
age and
gender.
Patients were evaluated for the
effects of exposure to a lavender
oil atmosphere on levels of pain,
anxiety, depression and perceived
sense of well-being. On three
different days, prior to and after a
60-minute session involving no
intervention (as a control),
exposure to an atmosphere
humidified with water (as a
control) or to an atmosphere
humidified with 3% lavender oil
vapour, each patient was
evaluated using 11-point verbal
analogue scales and vital signs
were also measured.
Compared to the no-intervention
control small non significant
decreases in blood pressure and
heart rate, and decreases in pain
and anxiety, as well as an
improvement in sense of well-
being, were observed after both
water humidification and
lavender oil treatment (Louis &
Kowalski 2002).
Cardiovascular effects
Clinical
question
Patients
Intervention
Outcome
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 38/45
Clinical
question
Patients
Intervention
Outcome
To identify the
effects of
aromatherapy
on blood
pressure and
stress
responses of
clients with
essential
hypertension.
Patients
(n=52) with
essential
hypertension
at random
assigned to
an essential
oil group, a
placebo group
and a control
group.
The application of aromatherapy
was the inhalation method of
blending oils with lavender,
ylang-ylang, and bergamot once
daily for 4 weeks. To evaluate the
effects of aromatherapy, blood
pressure and pulse were
measured two times a week and
serum cortisol levels,
catecholamine levels, subjective
stress and state anxiety were
measured before and after
treatment in the three groups.
The blood pressure, pulse,
subjective stress state anxiety
and serum cortisol levels among
the three groups were
significantly statistically
different. The differences of
catecholamine among the three
groups were not significant
statistically.
The results suggest that the
inhalation method using
essential oils can be considered
an effective nursing intervention
that reduces psychological stress
responses and serum cortisol
levels, as well as the blood
pressure of clients with essential
hypertension (Hwang 2006).
4.2.3.
Clinical studies in special populations (e.g. elderly and children)
Purpose
Patients
Intervention
Outcome
To study the
influence of
lavender oil
on stress in
newborns.
Five-day-old
human
infants'
responses to
heelstick
stress
(n=83).
Infants were assessed with
behavioural and physiological
indices. The subjects were divided
randomly into three groups: the
LAV group, who were presented
with artificial odour of lavender
during the heelstick; the MILK
group, who were presented with
artificial odour of milk during the
heelstick; and the CONT group,
who were presented with no
special odours.
The CONT group showed more
adrenocortisol release in saliva
than the other groups (p<0.05),
but there were no differences
between the two odours
(lavender and milk) (Kawakami
et al. 1997).
To study the
influence of
lavender oil
on autistic
behaviour in
children.
Twelve
children with
autism and
learning
difficulties (2
girls and 10
boys aged
between 12
years 2
months to 15
years 7
A within subjects repeated
measures design: 3 nights when
the children were given
aromatherapy massage with
lavender oil were compared with
14 nights when it was not given.
The children were checked every
30 min throughout the night to
determine the time taken for the
children to settle to sleep, the
number of awakenings and the
Repeated measures analysis
revealed no differences in any of
the sleep measures between the
nights when the children were
given aromatherapy massage
and nights when the children
were not given aromatherapy
massage. The results suggest
that the use of aromatherapy
massage with lavender oil has
no beneficial effect on the sleep
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 39/45
Purpose
Patients
Intervention
Outcome
months) in a
residential
school.
sleep duration. One boy's data
was not analyzed owing to
lengthy absence.
patterns of children with autism
attending a residential school. It
is possible that there are greater
effects in the home environment
or with longer-term
interventions (Williams 2006).
To examine
the
effectiveness
of an
aromatherapy
intervention
on the
reduction of
children's
distress in a
perianesthesia
setting.
The sample
included
children with
and without
developmenta
l disabilities
who
underwent
(mostly
orthopaedic)
surgery
(n=94: age:
7-17). Other
surgery
included
phenol or
Botox
injections,
skin surgery,
neurosurgery
or cranofacial
surgery.
Randomized, controlled, blinded
design. Subjects in the
intervention group received an
aromatherapy intervention of
lavender and ginger essential oils
as a comfort measure. A drop of
essential oil was placed on a
cotton ball and then taped to the
subject’s hospital gown
approximately 12 inches from the
face. A drop of essential oil was
also placed over a pulse point and
then covered with a small non-
occlusive adhesive dressing. The
dressing marked the application
site and also prevented
inadvertent removal of the oil by
surgery or anaesthesia
department staff. The essential
oils were reapplied
postoperatively if the subject was
in the operating room for longer
than 3 hours. The control group
received a placebo intervention of
jojoba oil. Distress was measured
at two times: before induction
and in the post anaesthesia care
unit (stay of 15 to 75 minutes)
using the Faces, Legs, Arms, Cry
and Consolability (FLACC) scale.
All subjects received standard
care, which included
pharmacologic treatment for
postoperative pain, anxiety,
nausea and vomiting.
The mean distress level was
lower for the children in the
essential oil group, but the effect
was not statistically significant
(p=.055). Parents' responses to
survey questions about
satisfaction with aromatherapy
did not differ between groups,
although open-ended comments
indicated a more positive opinion
of the benefits of the
intervention in the
aromatherapy group (Nord &
Belew 2009).
To investigate
the effects of
lavender oil
for insomnia,
on the
4 psycho-
geriatric
patients, 3 of
whom were
receiving
The hours of sleep of the patients
were measured for 2 weeks, then
measured for another 2 weeks
period after medication
withdrawal, and then measured
The amount of time spent asleep
was significantly reduced after
withdrawal of medication, but
that amount of time asleep
returned to the same level with
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 40/45
Purpose
Patients
Intervention
Outcome
duration of
sleep of
psycho-
geriatric
patients.
hypnotics or
tranquilizers.
for a final 2 weeks, during which
lavender oil was diffused into the
ward.
lavender oil as that under
medication. (Number
References: 4) (Hardy et al.
1995).
To determine
whether
smelling
lavender oil
decreases the
frequency of
agitated
behaviour in
patients with
dementia.
7 agitated
nursing home
residents with
advanced
dementia.
The study design was within-
subjects ABCBA (A = lavender oil,
B = thyme oil, C = unscented
grape seed oil): 4 weeks of
baseline measurement, 2 weeks
for each of the five treatment
conditions (10-week total
intervention time), and 2 weeks
of postintervention measurement.
Oil was placed every 3 hours on
an absorbent fabric sachet pinned
near the collarbone of each
participant's shirt. The study was
performed in a long-term care
facility specifically for persons
with dementia.
Split-middle analyses conducted
separately for each patient
revealed no treatment effects
specific to lavender, no
treatment effects nonspecific to
pleasant smelling substances,
and no treatment effects
dependent on order of treatment
administration. There were no
differences between participants
with more and less intact
olfactory abilities.
There is significant evidence in
the neurologic and
neuropsychologic literature that
persons with dementia have
impaired olfactory abilities.
Concordant with this literature,
this study found no support for
the use of a purely olfactory
form of aromatherapy to
decrease agitation in severely
demented patients. Cutaneous
application of the essential oil
may be necessary to achieve the
effects reported in previous
controlled studies (Snow 2004).
Agitation was assessed every 2
days using a modified Cohen-
Mansfield Agitation Inventory.
Olfactory functioning was
assessed with structured olfactory
identification and discrimination
tasks and with qualitative
behavioural observation during
those tasks.
Clinical
question
Patients
Intervention
Outcome
To what
extent
lavender oil
affects
agitation in
psycho-
geriatric
patients?
Patients
(mean age 79
+
6.3y)
meeting ICD-
10 diagnostic
criteria for
severe
dementia and
suffering from
agitated
Patients were included in a
placebo-controlled study. During
a total of 10 daily treatment
sessions a stream of 2% lavender
oil vapour, alternated every other
day with placebo (water) was
diffused into the community area
of a long-stay psychogeriatric
ward for a 2-hour period. For
each subject 10 PAS scores were
Compared to placebo, 9 patients
(60%) showed improvement
during exposure to lavender oil,
5 (33%) showed no change and
agitated behaviour worsened in
1 patient (7%). Group median
PAS scores showed that
lavender oil therapy produced a
modest improvement in agitated
behaviour compared to placebo
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 41/45
Clinical
question
Patients
Intervention
Outcome
behaviour
(minimum
score of 3
points on the
Pittsburgh
Agitation
Scale, PAS)
(n=15).
obtained: 5 during treatment and
5 during placebo periods.
(p=0.016) (Holmes et al. 2002).
To what
extent does
lavender oil
influence
postnatal
discomfort in
childbearing
mothers?
Mothers (total
n=635) after
normal child
birth.
Mothers (total n=635) used 6
drops of pure lavender oil
(n=217) or a synthetic lavender
oil (n=213) or an inert substance
(205) as an additive to their daily
bath for 10 days in a randomized
single-blind study. Analysis of
daily VAS scores for perineal
discomfort was recorded. A power
calculation was made on the level
of significance.
VAS scores revealed no
significant differences between
groups. However, there was a
trend between the 3rd and 5th
days, those women using
lavender oil reporting lower
mean scores for perineal
discomfort (Dale & Cornwell
1994).
To what
extent
lavender oil
improves the
mood and
anxiety in
hospital
stress?
Patients
admitted to
an intensive
care unit
(n=122). The
youngest
patient was 2
years old and
the oldest 92.
Patients were randomly allocated
to receive either massage,
massage with lavender oil (1%)
or a period of rest.
Patients who received lavender
oil massage reported
significantly greater
improvement in their mood and
perceived levels of anxiety
(p=0.05). The patients used a 4-
point scale to score their level of
anxiety, their mood and their
ability to cope with the present
situation. A pilot study was
conducted to test the reliability
and the validity of the final
assessment tool (Dunn et al.
1995).
To what
extent can
lavender
aroma
therapy be
beneficial in
the treatment
of behavioural
and
psychological
symptoms of
dementia
28 patients
with moderate
to severe
dementia
(nine men
and 19
women; mean
1 standard
deviation
[SD], 78 +/-
10 years;
MMSE 9 +/-
Patients with BPSD were divided
into two groups. One was treated
with lavender aromatherapy and
another group was not.
Overall conclusions on clinical
pharmacology and efficacy:
these conclusions should include
an assessment of the plausibility
of efficacy of the medicinal
product on the basis of long-
standing use and experience
(Fujii et al. 2008).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 42/45
Clinical
question
Patients
Intervention
Outcome
(BPSD)?
8).
4.3.
Overall conclusions on clinical pharmacology and efficacy
The anxiolytic activity of lavender oil has been studied in different conditions. Patients can be
considered as representative for ambulatory practice. The number of patients per study is low,
although in some trials a critical mass is obtained. Lavender oil is administered in dosage forms or
nebulised as aromatherapy. The former is more reliable as compared to the latter. Independently from
the form administered, lavender oil seems to positively influence anxiety and stress-related
restlessness. In one of the most recent studies (Woelk & Schläfke, 2010) patients with general anxiety
disorder are included. The study is organised according to good clinical practice. Patients are well
characterised, capsules with lavender oil are directly compared with lorazepam, and primary and
secondary outcomes are clearly distinguished. Before entering there was a one-week screening phase.
Results were calculated using the full analysis set (Intention to treat or ITT) as well as per protocol
(PP). However the number of patients is low and no power calculation is made. Furthermore no
placebo arm was included. Therefore it is not possible to grant a well-established use for lavender.
Lavender oil has been studied in special populations like newborn children, children with autistic
behaviour, psychogeriatric patients and hospitalised patients with positive outcomes. However the
study populations are small and might be too diverse.
5.
Clinical Safety/Pharmacovigilance
5.1.
Overview of toxicological/safety data from clinical trials in humans
In clinical studies involving patients treated orally with a lavender flower tincture (Buchbauer et al.
1993b), and patients or healthy volunteers treated with lavender oil either topically (Dale & Cornwell
1994; Yip & Tse 2004; Dunn et al. 1995) or by inhalation of the odour (Diego et al. 1998; Louis &
Kowalski 2002; Kane et al. 2004), only a few mild adverse events have been reported.
At a concentration of 16% in petrolatum, lavender oil did not produce any irritation after 48 hours in
the closed-patch test and produced no sensitization reactions in the maximization test (Opdyke 1976).
From evaluation of linalool and linalyl acetate for skin irritation in male volunteers no irritation was
observed with 20% linalool or up to 32% linalyl acetate, while mild irritation was observed with 32%
linalool. No sensitization reactions were observed in the human maximization test with linalool at
concentrations of 8% or 20%
in 50 volunteers, nor with 10% linalyl acetate in 131 volunteers. With
linalyl acetate at 12% and 20% no reactions were observed in 25 subjects (Bickers et al. 2003).
In very rare cases allergic reactions have been reported due to contact with lavender oil. Coulson &
Khan (1999) describe two case reports of mild facial ‘pillow’ dermatitis due to lavender oil allergy.
Lavender oil does not seem to be a major sensitizing substance (Hausen & Vieluf 1997).
A case of allergic reactions have been reported in young students (20 years). When an aromatherapy
student started massaging the feet of a client with a mixture of
Lavandula
, Origanum and Juniperus
oil, her hands started to tingle and became swollen with redness to her arms and throat area.
Shortness of breath occurred within 3 minutes of exposure. The symptoms were reversible upon
cleaning the skin of lavender oil (Maddocks-Jennings 2004).
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 43/45
Another case of contact dermatitis was reported after rubbing the face with hands that were not
cleaned from a massage gel, containing 5% benzylamine and lavender fragrance. Erythema, followed
by acute vesicular dermatitis developed (Rademaker 1994).
Three cases of gynecomastia in prepubertal boys were seen after topical application of products that
contained lavender and tea tree oils. The boys were between 4 and 10 years old. Exposure was as a
‘healing balm’ with lavender on the skin, styling gel containing lavender on hair and scalp and the use
of lavender-scented soap. Gynecomastia resolved after discontinuing of the therapy. No re-application
is mentioned. Nevertheless, causality was accepted between the topical use of the plant species
mentioned and the gynecomastia (Henley et al. 2007).
5.2.
Patient exposure
Lavender flowers and essential oil have been used for centuries. Exact exposure data related to the use
of registered preparations have not been retrieved.
5.3.
Adverse events and serious adverse events and deaths
There have been reports of contact dermatitis associated with lavender oil in shampoo, and facial
dermatitis after application of the oil to pillows for its sedative properties (Sweetman 2009).
5.4.
Laboratory findings
No data available.
5.5.
Safety in special populations and situations
No data available.
5.6.
Overall conclusions on clinical safety
There is no major concern about human toxicity due to lavender essential oil or lavender flowers.
Contact dermatitis may be possible in rare cases.
6.
Overall conclusions
Lavender essential oil as well as the dried lavender flowers can be considered as safe. There is no
major concern about the quality of the herbal substance and the herbal preparation thereof.
Experimental as well as clinical evidence converge to central nervous effects, more particularly related
to anxiety. There are many small- and larger-scale studies available with a patient population
representative for ambulatory practice, including children and elderly. Some criticism can be given to
the doses and the method of administration. Especially inhalation is difficult to quantify, although the
substances will be more directly delivered to the circulation. There are no major concerns on the safety
of lavender flowers or essential oil.
Lavender oil and flowers have been used for more than 30 years in the EU. A well established use
cannot be proposed for lavender flowers and oil in the treatment of general anxiety disorders (cf. ICD-
10 F 41.1). Although the quality of the studies increases with the time, the number of patients treated
with essential oil of lavender in RCTs is too low. No structured clinical research has been done on the
cutaneous use of
Lavandula
preparations. The use as bath additive of the oil has to be considered as
traditional.
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 44/45
The regulatory position of lavender flowers was discussed. There is a long-standing use of the flowers,
in a very wide range of therapeutic indications. Moreover, no authorized preparations with flowers were
reported in the EU countries. However, the effects for the relief of mild symptoms of mental stress and
exhaustion and to aid sleep are plausible on the basis of long-standing use and tradition, thus a
monograph could be established.
As the genotoxicity of lavender flowers and total essential oil was not appropriately tested, a
Community list entry cannot be established.
Annex
List of references
Assessment report on
Lavandula angustifolia
Mill., aetheroleum and
Lavandula
angustifolia
Mill., flos
EMA/HMPC/143183/2010
Page 45/45
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/lavandulae_flos_herbal.html
Copyright © 1995-2021 ITA all rights reserved.