COMMUNITY HERBAL MONOGRAPH ON
MELISSA OFFICINALIS
L., FOLIUM
To be specified for the individual finished product.
Well-established use
Traditional use
With regard to the registration application of
Article 16d(1) of Directive 2001/83/EC as
amended
Melissa officinalis
L., folium (melissa leaf)
i) Herbal substance
Cut , dried
ii) Herbal preparations
-
powdered herbal substance
-
Tincture (1:5 ; extraction solvent ethanol
45% V/V or m/m)
-
Liquid extract (1:1 ; extraction solvent
ethanol 45% V/V/ or m/m)
iii) Dry extracts that correspond to extracts
mentioned under ii)
Well-established use
Traditional use
Herbal substance or herbal preparations in solid
or liquid dosage forms for oral use or as herbal
tea.
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
1
The material complies with the Ph. Eur. monograph (ref. 01/2005: 1447)
2
The declaration of the active substance(s) for an individual finished product should be in accordance with relevant herbal
quality guidance.
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4.1.
Therapeutic indications
Well-established use
Traditional use
a)
Traditional herbal medicinal product for relief
of mild symptoms of mental stress and to aid
sleep.
b)
Traditional herbal medicinal product for
symptomatic treatment of mild gastrointestinal
complaints including bloating and flatulence.
The product is a traditional herbal medicinal
product for use in specified indications
exclusively based upon long-standing use.
4.2.
Posology and method of administration
Well-established use
Traditional use
Posology
Adolescents over 12 years of age, adults, elderly
Cut or powdered herbal substance: 1.5 - 4.5 g of
herbal substance 1 - 3 times per day.
Herbal tea: To make an infusion, pour 150 ml of
boiling water over 1.5 - 4.5 g of herbal substance.
Steep for 5 - 15 minutes. To be taken 1 - 3 times
daily.
Tincture: 2 - 6 ml 1 - 3 times daily.
Liquid extract: 2 - 4 ml 1 - 3 times daily.
Dried water or ethanol (45%) extracts in doses
corresponding to the posologies for tea, tincture
and liquid extracts above.
The use in children under 12 years of age is not
recommended (see 4.4. Special warnings and
precautions for use).
Duration of use
If the symptoms persist during the use of the
medicinal product, a doctor or a qualified health
care practitioner should be consulted.
Method of administration
Oral use.
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4.3.
Contraindications
Well-established use
Traditional use
Hypersensitivity to the active substance.
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
The use in children under 12 years of age is not
recommended because data are not sufficient and
medical advice should be sought.
For tinctures and liquid extracts containing
ethanol, the appropriate labelling for ethanol,
taken from the ‘Guideline on excipients in the
label and package leaflet of medicinal products
for human use’, must be included.
4.5.
Interactions with other medicinal products and other forms of interaction
Well-established use
Traditional use
No data available.
4.6.
Pregnancy and lactation
Well-established use
Traditional use
Safety during pregnancy and lactation has not
been established.
In the absence of sufficient data, the use during
pregnancy and lactation is not recommended.
4.7.
Effects on ability to drive and use machines
Well-established use
Traditional use
May impair ability to drive and use machines.
Affected patients should not drive or operate
machinery.
4.8.
Undesirable effects
Well-established use
Traditional use
None known.
If adverse reactions occur, a doctor or a qualified
health care practitioner should be consulted.
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Well-established use
Traditional use
No case of overdose has been reported.
5.1.
Pharmacodynamic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.2.
Pharmacokinetic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.3.
Preclinical safety data
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended, unless
necessary for the safe use of the product.
Data from
in vitro
and animal studies indicate that
the water extract of
Melissa officinalis
may
inhibit the activity of thyroid stimulating hormone
(TSH). The clinical relevance of these findings is
not known.
Tests on reproductive toxicity, genotoxicity and
carcinogenicity have not been performed.
Well-established use
Traditional use
Not applicable.
31 October 2007
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Assessment Report
1.
INTRODUCTION
1.1
Description
•
Melissa officinalis
L., folium is the dried leaf of
Melissa officinalis
L. [European
Pharmacopoeia].
2.
TRADITIONAL MEDICINAL USE
2.1
Information on period of medicinal use in the Community regarding the specified
Melissa officinalis
L., leaf has been used in Europe internally as a mild sedative and to relieve minor
gastrointestinal complaints for a very long time e.g. [Madaus, 1938; Hoppe, 1958; Steinegger and Hänsel,
1972; British Herbal Pharmacopoeia, 1983; Hänsel et al., 1993; ESCOP, 2003]. It is often used in
combination products.
2.2
Type of tradition where relevant
European phytotherapy.
2.3
Bibliographic/expert evidence on the medicinal use
A. Indication: For relief of mild symptoms of mental stress and to aid sleep
Medicinal use of
Melissa officinalis
L., leaf has been recorded in the following handbooks:
The Complete German Commission E Monographs
[Blumenthal, 1998].
Oral dose
: 1.5 – 4.5g of herb per
cup of tea, as needed, several times daily.
Duration of use
: No information.
Lehrbuch der Biologischen Heilmittel
[ Madaus, 1938].
Daily oral dose:
3.2 – 4.8 g as herbal tea for
infusion.
Duration of use
: No information.
Drogenkunde
[Hoppe, 1958].
Daily oral dose:
No information.
Duration of use
: No information.
ESCOP Monograph
[2003].
Daily oral dose:
2 – 3 g of the drug as an infusion, two to three times daily.
Tincture (1:5 in 45% ethanol), 2-6 ml three times daily. Other equivalent preparations.
Duration of use
: No
restriction.
Herbal medicine.
Expanded Commission E Monographs
[Blumenthal, 2000].
Oral dose
: 1.5 – 4.5g cut herb
several times daily. Infusion: 1.5-4.5 g in 150 ml. Fluidextract 1.1 (g/ml):1.5-4.5ml. Native dry extract 5.0-
6.0:1 (w/w): 0.3-0.9 g.
Duration of use
: No information.
Herbal Drugs
and Phytopharmaceuticals
[Wichtl, 2004].
Oral dose
: Crude drug 1.5 – 4.5 g several times
daily. Corresponding amount of preparations.
Duration of use
: No information.
Lehrbuch der Phytotherapie
[Weiss, 1991].
Daily oral dose:
No information.
Duration of use:
No
information.
Pharmakognosie
[Steinegger and Hänsel, 1992].
Oral dose
: 1.5g crude drug for preparation of tea.
Duration of use
: No information.
Herbal medicine
[Weiss and Fintelmann, 2000].
Daily oral dose
: 4 teaspoons (≈ 4 g) of the crude drug for
preparation of tea.
Duration of use
: No information.
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indications
British Herbal Compendium (Bradley, 2006). Dosage: Three time daily: 2-4g dried leaf as an infusion;
liquid extract (1:1 in 45% alcohol) 2-4 ml; or equivalent preparation.
WHO Monographs
[2002].
Daily oral dose:
Infusion: 1.5 – 4.5g crude drug per cup several times daily as
needed; 45% alcohol extract (1:1): 2-4ml three times daily; tincture (1:5 in 45% alcohol): 2-6 ml three times
daily.
Duration of use
: No information.
Herbal medicines a guide for healthcare professionals
[Barnes
et al
., 2002].
Daily oral dose:
1.5 – 4.5 g
dried herb as infusion in 150 ml water several times daily.
Duration of use
: No information.
Encyclopedia of common natural ingredients
[Leung and Foster, 1996].
Oral dose:
1.5 – 4.5 g. dried leaves
for tea infusion.
Duration of use
: No information.
Hagers Handbuch
[Hänsel
et al.
, 1993].
Daily oral dose:
1.5 – 4.5g as tea several times a day.
Duration of
use:
No information.
British Herbal Pharmacopoeia [1983].
Oral dose:
thrice daily: 2-4g dried leaves or by infusion. Liquid
extract (1:1 in 45% alcohol) 2-4 ml. Tincture (1:5 in 45% alcohol) 2-6ml.
Medicinal and traditional use for treatment of insomnia and nervous restlessness is also described in a
review [Koch-Heitzmann and Schultze, 1988].
Dosage
: 1.5 – 2 g crude drug for preparation of tea.
B. Indication: For relief of minor gastrointestinal complaints
Medicinal use of
Melissa officinalis
L., leaf for relief of gastrointestinal complaints is recorded in the
handbooks cited above:
The Complete German Commission E Monographs
(relief of functional
gastrointestinal complaints)[Blumenthal, 1998],
Lehrbuch der Biologischen Heilmittel
(carminative,
indigestion)[Madaus, 1938], D
rogenkunde
(stomachic, carminative)[Hoppe, 1958],
ESCOP Monograph
(symptomatic treatment of digestive disorders such as spasms)[2003],
Herbal Drugs
and
Phytopharmaceuticals
(gastrointestinal disorders of nervous origin)[Wichtl, 2004],
Pharmakognosie
(spasmolytic)[Steinegger and Hänsel, 1972],
WHO Monographs
(caminative for gastrointestinal
disorders)[2002],
Herbal medicines A guide for healthcare professionals
(carminative, gastrointestinal
disorders)[Barnes
et al
., 2002],
Encyclopedia of common natural ingredients
(carminative, antispasmodic,
stomachic)[Leung and Foster, 1996],
Hagers Handbuch
(functional gastrointestinal disorders)[Hänsel
et al.
,
1993], British Herbal Pharmacopoeia, 1983 (carminative, antispasmodic, flatulent dyspepsia, dyspepsia
associated with anxiety or depressive states) and British Herbal Compendium (digestive ailments such as
dyspepsia, eructation and flatulence)[Bradley, 2006].
The dosage is the same as for indication A. This indication is also described in the review [Koch-Heitzmann
and Schultze, 1988].
2.4
Assessor´s overall conclusion on the traditional medicinal use
Traditional medicinal use of
Melissa officinalis
L, leaf, in the form of powdered herbal substance, herbal tea
or ethanol extracts, for the relief of mild symptoms of mental stress and to aid sleep is well documented in a
number of handbooks.
Traditional medicinal use of
Melissa officinalis
L, leaf, in the form of powdered herbal substance, herbal tea
or ethanol extracts, for the symptomatic relief of mild gastrointestinal complaints including bloating and
flatulence is well documented in a number of handbooks.
The requirement of medicinal use in these indications for at least 30 years (15 years within the Community)
according to Directive 2004/24/EC is considered fulfilled.
In both indications, the following dosages have been recorded:
Herbal substance, cut or powdered: 1.5-4.5 g up to 3 times daily.
Herbal substance as a herbal tea: 1.5-4.5 g up to 3 times per day.
Liquid extract (1:1; extraction solvent 45% ethanol): 2-4 ml up to 3 times per day.
Tincture (1:5; extraction solvent 45% ethanol): 2-6ml up to 3 times per day.
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2.5
Bibliographic review of safety data of the traditional herbal medicinal substance
The following two major electronic databases were searched on 14 December 2006 with the search term
“melissa OR lemon balm”. Results:
PubMed: 157 references obtained.
Toxline: 128 references obtained.
Out of these references, no case reports on adverse reactions or other signals of safety concern in
connection with
Melissa officinalis
L., folium were identified.
2.5.1
Patient exposure
Products containing
Melissa officinalis
L., folium, appear to be available in most Member States. The
products have various regulatory statuses. A considerable patient/consumer exposure must be anticipated
although no exact figures can be given.
The ESCOP Monograph [2003] cites a study which comprised 20 healthy volunteers who were treated with
daily single doses of 300, 600 or 900 mg of an extract of Melissa leaf (30 % methanol). No adverse effects
were reported.
In another experimental study, 20 healthy volunteers were given 600, 1000 or 1600 mg of dry, powdered
leaf as single doses. No adverse effects were reported [Kennedy
et al.
, 2003].
A third experimental study comprised 18 healthy volunteers who received single doses of 300 mg or 600
mg of a 30 % aqueous methanol extract of the leaves. No adverse effects were reported [Kennedy
et al
.,
2004].
In a placebo-controlled study, 21 Alzheimer patients were given a daily dose of 60 drops of a 50 %
ethanolic extract (1:4) for 16 weeks. There was no statistically significant difference between the treated
group and the placebo group with respect to adverse effects, with the exception of agitation which was more
frequent in the placebo group [Akhondzadeh
et al
., 2003a]
This study was also published in another journal, but here it is said that the extract was prepared with 45 %
ethanol (1:1) and the daily dose was 60 drops for 4 months. The following adverse effects were observed:
vomiting (3), dizziness (1), wheezing (2), agitation (1), nausea (1) and abdominal pain (2). Agitation was
more frequent in the placebo group than in the verum group (6 vs 1) [Akhondzadeh
et al.
, 2003b].
2.5.2. Adverse effects.
Adverse effects have been reported in one clinical study (see above) [Akhondzadeh
et al.
, 2003b]. No other
reports have been identified.
2.5.3. Serious events and deaths.
None reported.
2.5.4.1 Intrinsic (including elderly and children)/extrinsic factors
No data available.
2.5.4.2 Drug-drug interactions and other interactions
No data available.
2.5.4.3. Use in pregnancy and lactation
No data available.
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2.5.4.4 Overdose
No data available.
2.5.4.5 Drug abuse
No data available.
2.5.4.6 Withdrawal and rebound
No data available.
2.5.4.7 Effects on ability to drive or operate machinery
No data available. Theoretically, products containing
Melissa officinalis
L., folium, may cause drowsiness.
This risk may increase in combination with alcohol or other sedatives or if excessive doses are taken.
2.5.4.8 Contra-indications
Hypersensitivity to the active substance.
2.5.5. Non-clinical safety data
2.5.5.1 Overview of available data regarding
Melissa officinalis
L., folium, preparation(s) and
relevant constituents thereof
Acute toxicity
.
No data available.
Repeated dose toxicity
.
No data available.
Genotoxicity
.
Negative results in the Ames test is reported for a 70 % aqueous ethanolic tincture of Melissa leaf [ESCOP,
2003].
No genotoxic effects were observed from a 20 % tincture in a somatic segregation assay using the diploid
strain
Aspergillus nidulans
D-30 [ESCOP, 2003].
No information on carcinogenicity, reproductive or developmental toxicity is available.
2.5.6 Assessor´s overall conclusions on safe use
Both non-clinical and clinical information on the safety of
Melissa officinalis
L., folium is scarce. As there
is no information on reproductive and developmental toxicity the use during pregnancy and lactation cannot
be recommended. Minimum required data on mutagenicity (Ames’ test) are not available for the tea (water
extract) or for the traditionally used 45 % ethanol extract (liquid extract or tincture).
Conventional clinical safety data are virtually absent. However, longstanding medicinal use and experience
of
Melissa officinalis
L., folium has been documented within the Community. During this time, no clear
clinical signals that
Melissa officinalis
L., folium is harmful under normal conditions of use have been
identified. As no data on use in children are available, products containing
Melissa officinalis
L., folium
cannot be recommended for use in children below the age of 12 years.
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3
Constituents
.
Essential oil.
0.06 – 0.8 % containing monoterpene aldehydes, mainly citral, neral and citronellal [ESCOP,
2003, Hänsel
et al
., 1993].
Sesquiterpene derivatives.
β-Caryophyllen and Germacren-D (10 % each in the essential oil) [Wichtl, 2004]
Monoterpene glycosides
[ESCOP, 2003].
Flavonoids
with glycosides of luteolin, quercetin, apigenin and kaempferol [ESCOP, 2003].
Phenylpropanoids
including hydroxycinnamic acid derivatives such as caffeic and chlorogenic acids and in
particular rosmarinic acid (up to 6 %) [ESCOP, 2003; WHO monograph, 2002]. European Pharmacopoeia
requires a minimum content of hydroxycinnamic derivatives, expressed as rosmarinic acid, of 4.0 %.
Triterpenes
including ursolic and oleanolic acids [ESCOP, 2003].
Tannins
[Hänsel
et al.
, 1993].
3.1
Overview of pharmacological effects of
Melissa officinalis
L., folium, preparations and
relevant constituents thereof
Pharmacodynamics
The following pharmacodynamic properties have been reported:
The essential oil exhibited spasmolytic activities on isolated guinea pig ileum, rat duodenum and vas
deferens, and on the jeujenum and aorta of rabbits. It also had relaxant effects on guinea pig tracheal muscle
and inhibited phasic contractions of an electrically stimulated myenteric plexus longitudinal muscle
preparation [ESCOP, 2003].
A 30 % aqueous ethanolic extract (1:3.5) at concentrations of 2.5 ml/l and 10 ml/l did not show any
significant antispasmodic activity when tested on contractions of the guinea pig ileum induced by
acetylcholine and histamine [ESCOP, 2003].
A 30 % aqueous ethanolic extract showed a dose-dependent sedative effect up to a dose of 25 mg/kg bw
when administered intraperitoneally to mice. The same extract, at doses of 3 – 6 mg/kg bw, induced sleep in
mice treated with an sub-hypnotic dose of pentobarbital and also prolonged pentobarbital-induced sleep
[ESCOP, 2003].
Intraperitoneal administration of the essential oil to mice had no sedative effect and did not prolong
pentobarbital-induced sleeping time, but when orally administered it showed sedative and narcotic effects at
doses of 3.16 mg/kg or higher [ESCOP, 2003].
An ethanolic liquid extract was tested for its potential anti-ulcerogenic activity against indometacin-induced
ulcers in rats. It showed dose-dependent anti-ulcerogenic activity at oral doses of 2.5 – 10 ml/kg bw. Acid
output was reduced and mucin secretion increased. An increase in prostaglandin E
2
release and a decrease in
leukotrienes was observed. The anti-ulcerogenic effect was also confirmed histologically. The results were
interpreted as due to the flavonoid content of the plant and to its free radical scavenging activity [ESCOP,
2003].
Antiviral activity, anti-inflammatory activity of rosmarinic acid, antimicrobial activity of the essential oil
and free radical scavenging properties have also been reported [ESCOP, 2003].
The ESCOP monograph cites an evaluation of human CNS cholinergic receptor binding activity of an
ethanolic extract. The extract displaced
3
H-(
N
)-nicotine and
3
H-(
N
)-scopolamine from muscarinic and
nicotinic receptors in homogenates of human cerebral cortical cell membranes at an IC
50
of < 1 mg/ml. The
dry residue of a 30 % methanol extract, mixed with 10 % inert material, displaced
3
H-(
N
)-nicotine and
3
H-(
N
)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue at an IC
50
of
11 mg/ml and 4 mg/ml respectively.
An ethanolic extract had no effect on the amplitude and frequency of slow waves in circular smooth muscle
of mouse small intestine [Storr
et al
., 2004].
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The essential oil of
Melissa officinalis
L. and its main component citral inhibited contractions of isolated rat
ileum caused by KCl (80 mM), acetylcholine (320 nM) and 5-HT (1.28 μM) in a concentration-dependent
manner with an IC
50
of approximately 20 ng/ml. [Sadraei
et al.
, 2003].
Oral daily doses of 2 g/kg bw of an aqueous extract of
Melissa officinalis
L., folium, were given to
hyperlipidemic rats for 28 days. Total cholesterol, total lipid, alanine transaminase, aspartate transaminase
and alkaline phosphatase in blood serum were reduced. The levels of lipid peroxidation in the liver tissue
were also reduced but the levels of glutathione in this tissue increased. Morphological studies of the liver
showed a decrease of hyperlipidemia-derived degenerative changes such as vacuolization, picnotic nuclei,
mononuclear cell infiltration and rupturing in the endothelium of the central veins in the hepatocytes. The
extract thus exerted a hypolipidemic effect and showed a protective effect on the liver [Bolkent
et al.
,
2005].
Data from
in vitro
and animal studies indicate that the water extract of
Melissa officinalis
may inhibit the
activity of thyroid stimulating hormone [Santini et al 2003; Benvenga 2003; Auf’molk et al 1985; Auf’molk
et al 1984; Sourgens et al 1982]. The clinical relevance of these finding is not known.
3.1.1 Assessor’s comments on pharmacological effects of
Melissa officinalis
L., folium,
preparations and relevant constituents
Available pharmacodynamic data on the traditionally used ethanol and water extracts are, at best,
inconclusive and cannot be considered to support the traditional indications.
3.2
Clinical studies
The ESCOP Monograph [2003] cites a study which comprised 20 healthy volunteers who were treated with
daily single doses of 300, 600 or 900 mg of an extract of Melissa leaf (30 % methanol). Cognitive
performance was assessed each day in a pre-dose testing session (baseline) and 1, 2.5, 4 and 6 hours after
treatment. The Cognitive Drug Research computerized test battery was used supplemented by two serial
subtraction tasks. Subjective mood was measured by Bond-Lader visual analogue scales. Significant
improvement of quality of attention was observed at all times after a dose of 600 mg of the extract (p =
0.0001 to p = 0.049). Significant decreases in the quality of working memory and secondary memory were
seen 2.5 and 4 hours after the higher doses (p = 0.0005 to p = 0.05). Reduction of working memory was
more pronounced at 1 and 2.5 hours after the higher doses. Self-rated calmness was elevated significantly
after 1 and 2.5 hours by the lowest dose (p = 0.01 to p = 0.05) while alertness was significantly reduced at
all time points (p = 0.001 to p = 0.05). [Kennedy
et al.
, 2003].
Another experimental study comprised 18 healthy volunteers who received single doses of 300 mg or
600 mg of a 30 % aqueous methanol extract of the leaves. The participants were subjected to mild
laboratory-induced psychological stress at 1 hour after treatment and the effect on mood and cognitive
performance assessed as in the previous tests. The 600 mg dose ameliorated the negative mood effects of
the stress with significantly increased self-ratings of calmness and reduced self-ratings of alertness. In
addition, a significant increase in the speed of mathematical processing with no reduction in accuracy was
observed after ingestion of the 300 mg dose [Kennedy
et al.
, 2004].
In a randomized, placebo-controlled study, 21 Alzheimer patients were given a daily dose of 60 drops of a
50 % ethanolic extract (1:4) for 16 weeks. The patients were ≥ 65 years of age with a score of 12 on the
cognitive subscale of Alzheimer´s Disease Assessment Scale (ADAS-cog) and 2 on the Clinical Dementia
Rating (CDR). At the end of the test, the Melissa extract produced a significantly better outcome on
cognitive functions than placebo (ADAS-cog = 1. F = 6.93, p = 0.01. CDR = 1. F = 16.78. p<0.0001)
[Akhondzadeh
et al.
, 2003b].
This study was also published in another journal, but here it was said that the extract was prepared with
45 % ethanol (1:1) and the daily dose was 60 drops for 4 months. The result was the same as in the
preceding report. [Akhondzadeh
et al
., 2003a].
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3.2.1 Assessor’s comments on clinical studies of
Melissa officinalis
L., folium, preparations and
relevant constituents
The 2 clinical studies by Kennedy et al [2003; 2004] were performed on a methanol extract which is not
covered by the monograph. The studies of effects on cognitive functions are of questionable relevance for
the traditional medicinal use and considered insufficient to support a well-established use monograph.
The study by Akhonzadeh et al [2003a] on 21 Alzheimer patients is considered insufficient to support a
well-established use monograph in this indication.
4
ASSESSOR´S OVERALL CONCLUSIONS
The traditional use of
Melissa officinalis
L., folium for the relief of mild symptoms of mental stress and to
aid sleep is well documented in recognised handbooks. For the indication ‘symptomatic relief of
gastrointestinal complaints such as indigestion, flatulence and minor spasms’ there is sufficient evidence of
traditional use. Products containing
Melissa officinalis
L., folium, are currently available in most Member
States. The requirement of medicinal use for at least 30 years (15 years within the Community) according to
Directive 2004/24/EC is considered fulfilled. Many of the products commercially available are combination
products with other herbal substances/preparations.
There is very little information on toxicity and only a few clinical studies have been published, all
comprising a small number of participants. There is insufficient information on genotoxicity,
carcinogenicity, reproductive and developmental toxicity. Use during pregnancy and lactation can thus not
be recommended.
Insufficient data on use in children are available therefore products containing
Melissa officinalis
L., folium
are not recommended for use in children below the age of 12 years.
Conventional clinical safety data are virtually absent, however, longstanding medicinal use and experience
of
Melissa officinalis
L., folium have been documented within the Community. No clinical signals that
Melissa officinalis
L., folium is harmful under normal conditions of use have been identified.
In view of the empirically acknowledged sedative properties of
Melissa officinalis
L., folium a warning for
use in connection with driving of cars and operation of machinery is advisable.
A specific preparation of
Melissa officinalis
L., consisting of a highly purified, dry aqueous extract (70:1) of
the leaf, is available in some Member States for treatment of herpes infections. The information on
manufacture and constituents is Limited. The only information available in the public domain is published
in Wölbling and Leonhardt (1994), in which the herbal substance is stated to comply with the monograph in
the German Pharmacopoeia. Extraction is performed with water and the extract is further purified by
chromatography but no details of this process are available. The dried extract is analyzed by HPLC and
contains caffeic acid, chlorogenic acid and rosmarinic acid as major components; no details are given. The
extract is standardized with respect to antiviral activity using the plaque inhibition test. Some clinical trials
have been reported on this product [Vogt
et al.,
1991; Wölbling and Leonhardt, 1994; Koytchev
et a.l
,
1999]. The clinical data for this specific product are not considered transferable to other products in the
form of a well-established use-monograph. It is questionable whether this highly purified extract should be
considered to be a ‘herbal medicinal product’ or a (combination) product of chemically defined
substance(s).
Sufficient data to develop a Community monograph on the traditional use of
Melissa officinalis
L., folium
are available. As the minimum required data on mutagenicity (Ames’ test) are not available, an inclusion to
the Community list of traditional herbal substances and preparations is not recommended.
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Source: European Medicines Agency
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