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Lemon balm (Melissa officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration

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An evidence-based systematic review including written and statistical analysis of scientific analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetic/dynamics, interactions, adverse effect, toxicology, and dosing.
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Catherine Ulbricht, PharmD, MBA(C), Column Editor
Lemon Balm (Melissa officinalis L.):
An Evidence-Based Systematic Review
by the Natural Standard Research Collaboration
Thomas Brendler, BA
Joerg Gruenwald, PhD
Benjamin Kligler, MD, MPH
David Keifer, MD
Tracee Rae Abrams, PharmD
Jen Woods, BS
Heather Boon, BScPhm, PhD
Catherine DeFranco Kirkwood, MPH, CCCJS-MAC
Ethan Basch, MD
Hope J. Lafferty, AM
Catherine Ulbricht, PharmD
Dana A. Hackman, BS
for the Natural Standard Research Collaboration
Thomas Brendler is affiliated with PlantaPhile, Berlin. Joerg Gruenwald is affili-
ated with Phytopharm Consulting. Benjamin Kligler is affiliated with Continuum Cen-
ter for Health and Healing. David Keifer is affiliated with the University of Arizona.
Tracee Rae Abrams is affiliated with the University of Rhode Island. Jen Woods is
affiliated with Northeastern University. Heather Boon is affiliated with the University
of Toronto. Catherine DeFranco Kirkwood is affiliated with the MD Anderson Cancer
Center. Ethan Basch is affiliated with the Memorial Sloan-Kettering Cancer Center.
Hope J. Lafferty is affiliated with the Memorial Sloan-Kettering Cancer Center.
Catherine Ulbricht is affiliated with Massachusetts General Hospital. Dana A. Hack-
man is affiliated with Northeastern University.
Natural Standard ( Copyright 2005. Reprinted with
Journal of Herbal Pharmacotherapy, Vol. 5(4) 2005
Available online at
doi:10.1300/J157v05n04_08 71
ABSTRACT. An evidence-based systematic review including written
and statistical analysis of scientific literature, expert opinion, folkloric
precedent, history, pharmacology, kinetics/dynamics, interactions, ad-
verse effects, toxicology, and dosing.
KEYWORDS. Citronellae, English balm, Lamiaceae, Melissa officinalis
L., sweet balm
To prepare each Natural Standard review, electronic searches are
conducted in nine databases, including AMED, CANCERLIT, CINAHL,
CISCOM, the Cochrane Library, EMBASE, HerbMed, International
Pharmaceutical Abstracts, MEDLINE, and NAPRALERT. Search terms
include the common name(s), scientific name(s), and all listed syn-
onyms for each topic. Hand searches are conducted of 20 additional
journals (not indexed in common databases), and of bibliographies
from 50 selected secondary references. No restrictions are placed on
language or quality of publications. Researchers in the field of comple-
mentary and alternative medicine (CAM) are consulted for access to ad-
ditional references or ongoing research.
Selection Criteria
All literature is collected pertaining to efficacy in humans (regard-
less of study design, quality, or language), dosing, precautions, ad-
verse effects, use in pregnancy/lactation, interactions, alteration of
laboratory assays, and mechanism of action (in vitro, animal research,
human data). Standardized inclusion/exclusion criteria are utilized for
Data Analysis
Data extraction and analysis are performed by health care profes-
sionals conducting clinical work and/or research at academic centers,
using standardized instruments that pertain to each review section (de-
fining inclusion/exclusion criteria and analytic techniques, including
validated measures of study quality). Data are verified by a second re-
Review Process
Blinded review of reviews is conducted by multidisciplinary re-
search-clinical faculty at major academic centers with expertise in epi-
demiology and biostatistics, pharmacology, toxicology, complementary
and alternative medicine (CAM) research, and clinical practice. In cases
of editorial disagreement, a three-member panel of the Editorial Board
addresses conflicts, and consults experts when applicable. Authors of
studies are contacted when clarification is required.
Update Process
Natural Standard regularly monitors scientific literature and industry
warnings. When clinically relevant new data emerge, best efforts are
made to update content immediately. In addition, regular updates with
renewed searches occur every 3-18 months, variable by topic.
Synonyms/Common Names/Related Substances
Balm, balm mint, bee balm, blue balm, Citra, citronellae, citron-
melisse, common balm, cure-all, dropsy plant, English balm, folia
citronellae, folia melissae citratae, garden balm, gastrovegetalin,
hjertensfryd, honey plant, kneipp melisse pflanzensaft, Labiatae/
Lamiaceae (family), lemon melissa, lomaherpan, melissa, Melissa
officinalis,Melissa officinalis L., melissae, melissae folium, Melisse
(German and French), melissenblatt, melissengeist, sweet balm,
sweet mary, toronjil (Spanish), valverde boutons de fievre crème.
Natural Standard Review 73
Selected Combination Products
Abdomilon, Abdomilon N, Absimed, Agua del Carmen, Aktiv
Nerven-und Schlaftee, Anevrase, Aponatura Beruhigungs, Aponatura
Einschlaf, Aranidorm-S, Arterosan Plus, Avedorm, Baldracin,
Baldrian-Elixier, Baldrian-Krautertonikum, Baldriparan, Baldriparan
Beruhigungs, Baldriparan stark N, Balsamo Branco, Befelka-Tinktur,
Beruhigungstee, Biocarde, Bio-Garten Tee zur Beruhigung, Bio-
Garten Tropfen zur Beruhigung, Camomila, Canad, Caramelos
Agua del Carmen, Cardalept, Cardiaforce, Colominthe, Cough
Drops, Cura, Digestol Sanatorium, Doppelherz Melissengeist,
Doppelherz Tonikum, Dormarist, Dormiplant, Dragees pour la de-
tente nerveuse, Elixir Bonjean, Emmenoiasi, Especies Calmante,
Euvegal Entspannungs-und Einschlafdragees, Euvegal forte, Euvegal
N, Euviterin, Fargestium, Fluxoten, Gastregan, Gastrol S, Gastrosan,
Gutnacht, Heumann Beruhigungstee Tenerval N, Herz-und Kreisl-
auftonikum Bioflora, Hyperiforce comp, Iberogast, JuDorm, JuNeuron
S, Klosterfrau Melissengeist, Kneipp Krauter Taschenkur Nerven
und Schlaf N, Kneipp Nerven-und Schlaf- Tee, Kneipp Nerven-
und Schlaf-Tee N, Krauterdoktor Beruhigungstropfen, Krauterdoktor
Entspannungs-und Einschlaftropfen, Krauterdoktor Magen-
Darmtropfen, Krauterdoktor Nerven-Tonikum, Krauterdoktor
Rosmarin-Wein, Krauterhaus Mag Kottas Babytee, Krauterhaus
Mag Kottas Magen- und Darmtee, Krauterhaus Mag Kottas Nerven-
und Schlaftee, Krauterhaus Mag Kottas Wechseltee, Krautertee Nr
1, Krautertee Nr 141, Krautertee Nr 16, Krautertee Nr 201, Krautertee
Nr 209, Krautertee Nr 9, Lindofluid N, Lo-701, Luvased-Tropfen
N, Mag Doskar’s Magentonikum, Mag Doskar’s Nerventonikum,
Mag Kottas Beruhigungstee, Mag Kottas Krauterexpress-Nerven-
Schlaf-Tee, Mag Kottas Magen-Darmtee, Mag Kottas Nerven-
Beruhigungstee, Mag Kottas Schlaftee, Mag Kottas Tee fur stillende
Mutter, Mag Kottas Wechseltee, Mariazeller, Mediflor Tisane
Calmante Troubles du Sommeil No 14, Mediflor Tisane Circula-
tion du Sang No 12, Mediflor Tisane Pectorale d’Alsace, Me-
lissa comp., Melissa Specie Composta, Melissa Tonic, Melissengeist,
Melissin, Nervendragees, Nerven-Tee Stada N, Nervifloran,
Nervosana, Nyrene, Oxacnt N, Oxacant-sedativ, Pascosedon,
Passedan, Passelyt, Passiflora Composta, Phytoberidin, Phytogran,
Phytonoctu, Plantival, Plantival novo, Presselin Blahungs K 4 N,
Pronervon Phyto, Relax, Resolutivo Regium, RubieSed, Salus
Nerven-Schlaf-Tee Nr.22, Salusan, Santane D5, Santane N9, Schlaf-
und Nerventee, Sedacur, Seda-Grandelat, Sedantol, Seda-Plantina,
Sedariston, Sedaselect N, Sedasyx, Sedatol, Sedatruw S, Sedinfant
N, Seracalm, Sidroga Herz-Kreislauf-Tee, Sidroga Kindertee, Sidroga
Magen-Darm-Tee, Sidroga Nerven-und Schlaftee, Sirmiosta Nerven-
elixier N, Sol Schoum, Songha, Songha Night, Soporin, Species
nervinae, St Radegunder Beruhigungs-und Einschlaftee, St Rade-
gunder Fiebertee, St Radegunder Herz-Kreislauf- Tonikum, St
Radegunder Herz- Kreislaufunterstutzender Tee, St Radegunder
Magenberuhigungstee, St Radegunder Nerventee, St Radegunder
Nerven-Tonikum, St Radegunder Reizmildernder Magentee, St
Radegunder Rosmarin-Wein, Stullmaton, STW 5-II (bitter candy
tuft, matricaria flower, peppermint leaves, caraway, licorice root,
and lemon balm), STW-5-S (matricaria flower, peppermint leaves,
caraway, licorice root, and lemon balm), SX Valeriana comp,
Synpharma InstantNerventee, Teekanne Magen-und Darmtee, Teek-
anne Schlaf-und Nerventee, The Brioni, The Chambard-Tee, The
Franklin, Tisana Arnaldi, Tisana Cisbey, Tisana Kelemata, Tisane
antiflatulente pour les enfants, Tisane calmante pour les enfants,
Tisane des Familles, Tisane favorisant l’allaitement, Tisane Grande
Chartreuse, Tisane pour le coeur et la circulation, Tisane pour le
Foie, Tisane pour le sommeil et les nerfs, Tisane pour les enfants,
Tisane pour l’estomac, Tisane Purgative, Tisane relaxante, Tisane
Touraine, Vagostabyl, Valerina Day Time, Valerina Night- Time,
Valverde Dragees pour la détente, Wechseltee.
Brief Background
Lemon balm (Melissa officinalis) is an herb with a lemon scent na-
tive to southern Europe. Historically lemon balm has been said to
possess sedative/tranquilizing, anti-gas, fever-reducing, antibacte-
rial, spasmolytic, hypotensive, memory-enhancing, menstrual-in-
ducing, and thyroid-related effects and has been proposed by some
to be an herbal cure-all.1-3 The plant has been used for centuries in
various cultures internationally.4,5
Lemon balm has been used for its tranquilizing properties in Portu-
guese folk medicine and for anticancer properties in Cuban folk
Natural Standard Review 75
Lemon balm is member of the Lamiaceae family.7-10 Other mem-
bers of the Lamiaceae family include dittany, mint, sage, siderites,
and sweet marjoram.11
In vitro data suggest that lemon balm may contain high concentra-
tions of antioxidants.12
Lemon balm has been assigned to the FDA Generally Recognized
As Safe (GRAS) list in the United States. No serious side effects
have been reported, although there is limited research of long-term
effects. See Tables 1 and 2.
Evidence of harm is considered separately; the below grades apply
only to evidence of benefit.
Historical or Theoretical Uses Which Lack Sufficient Evidence
Analgesic,13 anorexia, anticholinergic,14,15 anti-gas,16 antihista-
minic, antihypertensive, antisecretory,17 antispasmodic,18-20 anti-
ulcerogenic,17 antiviral,7,9,9,19,21-26 anxiolytic,19,27 aromatic, atten-
tion deficit and hyperactivity disorder,28 cancer,6,17,29,30 chronic
bronchitis, chronic fatigue syndrome, colic, coughs, depression,19
digestive aid, fever reduction, flatulence, flatulent colic, gastroin-
testinal disorders, Graves disease,31-33 heart conditions, high blood
pressure, HIV,26 influenza, insect bites, insomnia,19,34-36 irregular
menstrual periods,16 irritable bowel syndrome, intestinal relaxant,15
memory enhancer,4,5,14 migraine, nausea, nervous palpitations,37
nervous stomach,37 neuralgia,19 neurasthenia, promoting menstrual
flow,33,38 promoting sweating, restlessness, sedative,13,19,34-36
shingles, skin irritations, sleep disorders,19,34-36 tension headache,
toothache, tranquilizer, vasodilatation, vomiting, wound healing
TABLE 1. Scientific Evidence for Common/Studied Uses
Indication Evidence Grade
Herpes simplex virus infections B
Agitation in dementia C
Anxiety C
Cognitive performance C
Colitis C
Dyspepsia C
Sleep quality C
Expert Opinion and Folkloric Precedent
In Europe, lemon balm has been widely used as a topical antiviral
treatment for genital and oral herpes, applied at the first sign of a
herpes flare-up or regularly for prevention. In Germany, the essen-
tial oil placed on the temples has been used to relieve headaches or
The German Commission E recommends lemon balm for nervous
sleep disorders and functional gastrointestinal complaints. The
European Scientific Cooperative on Phytotherapy (ESCOP) rec-
ommends its use for tenseness, restlessness, and irritability. Lemon
balm has been placed on the FDA Generally Regarded As Safe
(GRAS) list.
Natural Standard Review 77
TABLE 2. Natural Standard evidence-based validated grading rationale™
Level of Evidence Grade Criteria
A(Strong Scientific Evidence) Statistically significant evidence of benefit from > 2 properly
randomized trials (RCTs), OR evidence from one properly
conducted RCT AND one properly conducted meta-analysis, OR
evidence from multiple RCTs with a clear majority of the properly
conducted trials showing statistically significant evidence of
benefit AND with supporting evidence in basic science, animal
studies, or theory.
B(Good Scientific Evidence) Statistically significant evidence of benefit from 1-2 properly
randomized trials, OR evidence of benefit from 1 properly
conducted meta-analysis OR evidence of benefit from > 1
cohort/case-control/non-randomized trials AND with supporting
evidence in basic science, animal studies, or theory.
C(Unclear or conflicting scientific evidence) Evidence of benefit from 1 small RCT(s) without adequate
size, power, statistical significance, or quality of design by
objective criteria,* OR conflicting evidence from multiple RCTs
without a clear majority of the properly conducted trials showing
evidence of benefit or ineffectiveness, OR evidence of benefit
from 1 cohort/case-control/non-randomized trials AND without
supporting evidence in basic science, animal studies, or theory,
OR evidence of efficacy only from basic science, animal studies,
or theory.
D(Fair Negative Scientific Evidence) Statistically significant negative evidence (i.e., lack of evidence
of benefit) from cohort/case-control/non-randomized trials, AND
evidence in basic science, animal studies, or theory suggesting
a lack of benefit.
F(Strong Negative Scientific Evidence) Statistically significant negative evidence (i.e., lack of evidence
of benefit) from 1 properly randomized adequately powered
trial(s) of high-quality design by objective criteria.*
Lack of EvidenceUnable to evaluate efficacy due to lack of adequate available
human data.
* Objective criteria are derived from
validated instruments for evaluating study quality
, including the 5-point scale
developed by Jadad et al., in which a score below 4 is considered to indicate lesser quality methodologically
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of
reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials 1996; 17[1]:1-12
). See Table 4.
Listed separately in monographs in the “Historical or Theoretical Uses which Lack Sufficient Evidence” section.
Brief Safety Summary
Likely Safe: When used topically or orally in recommended doses
(up to 30 days) in otherwise healthy adults34,39 and when con-
sumed in amounts found in foods. Lemon balm has been assigned
Generally Regarded As Safe (GRAS) status in the United States
with a maximum level of 0.5% in baked goods.
Possibly Unsafe: During pregnancy or lactation or in pediatric pa-
tients, and when used in patients with thyroid disorders or in com-
bination with sedatives (theoretical).
Recommended doses are based on those most commonly used in
available trials, or on historical practice. However, with natural
products it is often not clear what the optimal doses are to balance
efficacy and safety. Preparation of products may vary from manu-
facturer to manufacturer, and from batch to batch within one man-
ufacturer. Because it is often not clear what the active components
of a product are, standardization may not be possible, and the clini-
cal effects of different brands may not be comparable.
Investigations of lemon balm have suggested that the percentage
of essential oil from the leaves can range from 0.08 to 0.25 mL/100
grams, and 0.06 to 0.167 mL/100 grams in the herb.40 The content
and quality of essential oils from lemon balm also may differ de-
pending upon the height and location of the harvest cut of a partic-
ular plant, the vegetation period of the plant, and also between
different populations of the plant. For example, the oil content in
lemon balm appears to be highest in the top third of the plant, and
the percentage of the constituents may be highest when the plant is
cut in the basipetal direction.40-47 Clinical trial data suggest that
different preparations of lemon balm may result in products, which
exhibit different properties depending on the process used for the
sample preparation.2
Lomaherpan®is a topical lemon balm extract (70:1) sold in Europe
that is standardized by bioassay.23,24 Herpilyn®, a topical prepara-
tion with equivalent standardization to the European products
(70:1), is sold in the United States. Doses used in other herbal
combinations are variable.
Studies have demonstrated that analysis of the different constitu-
ents of lemon balm may be achieved using methods such as gas
chromatography, mass spectroscopy, thin-layer chromatography,
plasma optical emission spectrometry and inductively coupled
plasma-source mass spectrometry, matrix solid-phase dispersion,
UV, 1R, 1H NMR, 13C NMR, and FAB MS.8,11,40,48-54 Several au-
thors have presented methods for identification,55-58 determination
of herbicide residues,59 and characteristics of adulterations.60 A
study of residue extraction from the whole leaves of lemon balm
by in vitro analysis by an isopropanol apparatus suggested that this
method is not appropriate for lemon balm.61
Adult Dosing (18 Years and Older)
Tea: A common dose of lemon balm is one cup of tea taken several
times per day as needed. Anecdotally, others have suggested 1.5 to
4.5 grams of lemon balm herb taken several times per day as a tea.
Tincture: A dosage of 2-6 mL three times per day (1:5 in 45% al-
cohol) has been used historically.
Liquid extract: Lemon balm extract in a dose of 60 drops per day
has been cited in research on patients with Alzheimer’s disease for
improvement in cognition.62
Leaves: A dosage of 8-10 grams per day has been used.
Combination products: The product Songha Night®, which in-
cludes 120 mg Valeriana officinalis extract and 80 mg lemon balm
extract, has been used as a sleep aid in a dosage of three tablets
taken nightly for 30 days.34 For anxiety, Klosterfrau Melissengeist®
[each teaspoonful (5 mL) contains essential oils of lemon balm (27
mg), orange peel (36 mg), cinnamon (16 mg), and myristica (4
mg)] has been taken as 0.23 mL/kg body weight, three times per
day for eight weeks.37 For dyspepsia, Iberogast®, a standardized
formula containing Matricata recutita,Iberis amara,Angelica
archangelica,Carum carvi,Silybum marianum, lemon balm,
Natural Standard Review 79
Chelidonium majus,Glycyrrhiza glabra, and Mentha piperita,
has been taken in a dosage of 20 drops, three times per day for a
minimum of four to eight weeks.63
Cream: Cream containing 1% of a standardized 70:1 extract, topi-
cally up to four times per day for 5 to 10 days has been studied for
the treatment of active viral herpes.22-24
Tea: Alternatively, a tea has been applied to herpes lesions with a
saturated cotton ball several times per day. The tea is prepared by
steeping 2-3 teaspoons (2-3 grams) of the finely cut leaf in 150 mL
boiling water for 5-10 min and then straining.
Pediatric Dosing (Younger Than 18 Years)
Insufficient available data.
Lemon balm preparations may contain trace amounts of lead. A
study evaluating metal dispersion in food crops suggested that the
soil in which some plants are grown may be contaminated by lead
from environmental pollution and therefore may cause the plant to
contain trace amounts of the element.64
The lack of genotoxic effects of aqueous or alcoholic extracts of
lemon balm on Aspergillus nidulans D-30 using a plate-incorpora-
tion assay has been noted.6
There are insufficient available data on chronic toxicity.
Individuals with known allergy/hypersensitivity to lemon balm should
avoid its use. Hypersensitivity reactions have been reported, including
contact dermatitis.65 Lemon balm extract had a weak sensitizing effect
in guinea pigs.66
Adverse Effects/Post Market Surveillance
General: Based on available research, oral forms have been reported
to be relatively well-tolerated when taken for up to 8 weeks.37 Evidence
for topical administration of cream suggested minimal side effects for
up to 10 days of application.22,24,39
Dermatologic: Contact dermatitis,65 local reddening, burning sensa-
tion, paresthesia, residual pigmentation,23 and dermal irritation24 on ap-
plication of cream have been reported. One case of irritation and one
case of exacerbation of herpes symptoms were reported when lemon
balm was applied topically.24
Neurologic: One clinical study reported the occurrence of head-
ache.37 One study cited that 1200 mg of lemon balm resulted in EEG
changes.67 One trial reported that 900 mg of lemon balm may reduce
alertness, so caution should be used when driving or operating heavy
machinery.20 In one clinical trial, the use of a Valeriana officinalis/
lemon balm combination was reported to cause mild adverse effects in
28.8% of patients, with sleep disturbances and tiredness cited as the
most common side effects (although sedative properties of Valeriana
officinalis alone are well-described and the additional effects of lemon
balm are not clear in this combination).13,34 AValeriana officinalis-
Humulus lupulus-lemon balm combination was reported to cause tired-
ness in isolated cases.68
Ocular/Otic: Anecdotal reports note the possibility of lemon balm
increasing intraocular pressure.
Cardiovascular: One randomized controlled trial reported the occurence
of palpitations.37
Endocrine: A pre-clinical study reported that constituents of lemon
balm may block the binding of thyroid-stimulating hormone (TSH) to
its receptor by acting both on the hormone and the receptor itself.69
Studies have suggested that patients with thyroid problems such as
Graves’ disease use caution due to the potential for thyroid hormone in-
hibition.27,31-33,38,69 Lemon balm may interfere with thyroid hormone
replacement therapy (theoretical).
Gastrointestinal: Cases of nausea and diarrhea have been reported.37)
Use cautiously in patients with thyroid problems such as Graves’
disease due to potential for thyroid hormone inhibition.27,31-33,38,69
Natural Standard Review 81
Use cautiously in patients with glaucoma as anecdotal reports have
suggested that lemon balm may increase intraocular pressure.
Use caution when driving or operating heavy machinery. Results
from one clinical study have suggested that lemon balm may re-
duce alertness at doses of 900 mg.20
Lemon balm preparations may contain trace amounts of lead. A
study evaluating metal dispersion in food crops suggested that the
soil in which some plants are grown may be contaminated by lead
from environmental pollution and therefore may cause the plant to
contain trace amounts of the element.64
Pregnancy and Lactation
Not recommended due to lack of sufficient data.27 Lemon balm
may elicit emmenagogic, antithyrotropic, and antigonadotropic ef-
fects (anecdotal).
Lemon Balm/Drug Interactions
Alcohol: In theory, alcohol use with lemon balm may augment the
sedative effects of alcohol.20,27 However, no additive effects of al-
cohol were shown when combined with a Valeriana officinalis-
Humulus lupulus-lemon balm combination product.68
Barbiturates: Lemon balm has been reported to increase the hyp-
notic effects of barbiturates in animal studies.13,27
Sedative agents: Based on preclinical studies70 and initial human
research,20 combination use of lemon balm with sedatives may re-
sult in additive effects.
Glaucoma medications: Based on anecdotal accounts, lemon balm
may increase intraocular pressure, thereby diminishing effects of
glaucoma medications.
Thyroid agents: In euthyroid rats, the administration of freeze-
dried extracts of lemon balm was reported to reduce pituitary and
serum thyroid stimulating hormone (TSH) concentrations.31-33
One study suggested that constituents of lemon balm may block
the binding of TSH to its receptor by acting on both the hormone
and the receptor itself.69 Lemon balm may interfere with thyroid
hormone replacement therapy (theoretical).
Nicotine and scopolamine: Lemon balm may displace drugs bound
to nicotinic and muscarinic receptors, as demonstrated in clinical
trials with the displacement of nicotine and scopolamine from
these receptors.2,14,20
Selective serotonin reuptake inhibitors (SSRIs): As demonstrated
in in vitro studies, lemon balm may inhibit concentrations of sero-
tonin and therefore may interact with drugs which affect concen-
trations of serotonin in vivo.15
Lemon Balm/Herb/Supplement Interactions
Sedative herbs and supplements: A study examining efficacy and
safety of herbal sedatives suggested that combination use of sed-
ative herbs with lemon balm may result in additive effects.70
Such herbs include ashwaganda root, calamus, calendula, Cali-
fornia poppy, capsicum, catnip, celery, cough grass, elecampane,
Siberian ginseng, German chamomile, goldenseal, gotu kola,
hops (Humulus lupulus), Jamaican dogwood, kava, sage, St.
John’s wort, sassafras, skullcap, shepherd’s purse, stinging net-
tle, valerian (Valeriana officinalis), wild carrot, wild lettuce, and
yerba mansa.
Herbs and supplements used for glaucoma: Anecdotal accounts
suggest that lemon balm may increase intraocular pressure, thereby
diminishing effects of glaucoma treatments.
Herbs that affect thyroid hormone: In euthyroid rats, the adminis-
tration of freeze-dried extracts of lemon balm was reported to re-
duce pituitary and serum TSH concentrations.31-33 One study
suggested that constituents of lemon balm may block the binding
of TSH to its receptor by acting both on the hormone and the
receptor itself.69
Lemon Balm/Lab Interactions
Thyroid Stimulating Hormone: In euthyroid rats, the administra-
tion of freeze-dried extracts of lemon balm was reported to re-
duce pituitary and serum TSH concentrations.31-33 One study
reported that constituents of lemon balm may block the binding
of TSH to its receptor by acting on both the hormone and the
receptor itself.69
Prolactin: In rats, prolactin serum levels and hypophyseal stores were
reduced by 40 mg/100 grams of a freeze-dried extract of lemon balm.33
Natural Standard Review 83
Constituents: The known major components of lemon balm are re-
ported to include hydroxycinnamic acid derivatives, particularly
rosmarinic acid, caffeic acids, chlorogenic acid, and metrilic
acid;11,38,49,71-73 tannins;7,9,21,74,75 flavonoids, including luteolin,
luteolin 7-O-beta-D-glucopyranoside, apigenin 7-O-beta-D-gluco-
pyranoside, and luteolin 3-O-beta-D-glucuronopyranoside;17,32,40,
45,48,52,76,77 monoterpene glycosides;78 sesquiterpenes, including
β-caryophyllene and germacrene;78 triterpenes;79 and volatile oils,
including citronellal, citral a (geranial), citral b (neral), methyl
citronellate, ocimene, citronellol, geraniol, nerol, β-caryophyllene,
β-caryophyllene oxide, linalool, and ethric oil.40,45,80-84 The vola-
tile oil comprises 0.5-0.1% of the plant by weight, and citronellal,
geranial, and neral constitute about 50-70% of this oil.80 Eugen-
ylglycoside has been isolated from lemon balm leaves.85 The
chemical composition of lemon balm tea yielded 10 mg/L of es-
sential oil (74% citral) and large amounts of polyphenol com-
pounds.86 Steam distillates of lemon balm callus cultures yielded
dehydroabietane and another diterpene hydrocarbon, with the rela-
tive proportion of those two compounds varying considerably dur-
ing cultivation passage.87
Antiviral effects: Studies have reported that aqueous extracts of
lemon balm exhibit antiviral effects against Newcastle disease vi-
rus, Semliki forest virus, influenza virus, myxoviruses, vaccinia,
and herpes simplex virus.7,9,21,25,51,74 Lemon balm extract and
rosmarinic acid have demonstrated antiviral properties against
HIV-1.26 Studies conducted to assess the antiviral effects of lemon
balm on Herpes simplex virus 1 have suggested that different ex-
tracts of the herb (M1, M2, M3, and M4) exhibit different effects
on the virus.51 Studies conducted to assess the antiviral effects of
lemon balm on Herpes simplex virus 2 suggest that the volatile oil
components of lemon balm inhibit replication of HSV-2.88 Lemon
balm’s antiviral effects are attributed to the tannin and polyphenol
constituents. Tannins are reported to possess antiviral proper-
ties7,9,21,25,74 as are rosmarinic, caffeic, and ferulic acids.7,51
Antibacterial/antifungal effects: The lemon balm constituent
rosmarinic acid was reported to impair in vivo activation of mouse
macrophages by heat-killed Corynebacterium parvum, as mea-
sured by the decreased capacity of the activated macrophages to
undergo the oxidative burst.73 In vitro analyses of the antimicr-
obial properties of lemon balm suggested that at a concentration of
500 microg/mL, the herb completely inhibits the growth of all
yeast species including, Torulaspora delbrueckii,Zygosaccharomyces
bailii,Pichia membranifaciens,Dekkera anomala, and Yarrowia
lipolytica.(50,89) Data from in vitro analyses have suggested that
lemon balm may be effective as an antibiotic against anaerobic
and facultative aerobic periodontal bacteria including, Porphyromonas
gingivalis,Prevotella spp., Fusobacterium nucleatum,Capnocyto-
phaga gingivalis,Veilonella parvula,Eikenella corrodens,Pepto-
streptococcus micros, and Actinomyces odontolyticus.90 Lemon
balm oils have been reported to demonstrate highest activity against
S. enterica (BA50 range, 0.0044-0.011%).91 Antibacterial activity
was reported to be expressed on a multiresistant strain of Shigella
Antiinflammatory effects: The paucity of clinical evidence makes
the assessment of the antiinflammatory effect of lemon balm diffi-
cult to verify.73,93 Rosmarinic acid has been reported to reduce paw
edema induced by cobra venom factor in rats and to inhibit passive
cutaneous anaphylaxis in rats at doses of 1-100 mg/kg by mouth.
Rosmarinic acid has been reported not to inhibit t-butyl
hydroperoxide-induced paw edema in the rat, indicating selectiv-
ity for complement-dependent processes.73
Antioxidant effects: In vitro data suggest that lemon balm contains
high concentrations of antioxidants (greater than 75 mmol/100
g).8,11,12,17,72,94 Lemon balm has been reported to demonstrate high
phenolics content and antioxidant properties (TEAC 4.06+/0.31
mM/QE 1370.09+/41.38 microM).95 Lemon balm extracts and
rosmarinic acid have both been reported to demonstrate antioxi-
dant properties in vitro,8,11,72 and rosmarinic acid and caffeic acid
have demonstrated significant antioxidant and immune modulat-
ing activities.10, 11, 72,73,93 During linoleic acid autoxidation and its
EDTA-mediated oxidation, lemon balm showed antioxidant activ-
ity.96 An in-vitro cytotoxicity assay demonstrated that lemon balm
oil was very effective against a series of human cancer cell lines
(A549, MCF-7, Caco-2, HL-60, K562) and one mouse cell line
(B16F10). Further antioxidant activity of lemon balm has been
reported as evidenced by the reduction of 1,1-diphenyl-2- picryl-
hydrazyl (DPPH).97 Studies have demonstrated that the cytopro-
tective effect of lemon balm extracts seen in rats was due in part to
Natural Standard Review 85
free-radical scavenging properties.10,17 Immunostimulating effects
of a lemon balm extract were also demonstrated.98 Inhibitory ef-
fects of rosmarinic acid from lemon balm on porcine pancreatic
amylase were reported in vitro.99
Antiprotozoal effects: Essential oils, monoterpenes, and sesquiterpenes
from lemon balm were tested on bloodstream forms of Leishmania
major and Trypanosoma major. These constituents were reported
to be about 50- to 80-fold more toxic to T. major than were human
HL-60 cells. None of the essential oils or terpenes were reported to
be more toxic to L. major than HL-60.78 Monoterpene and sesquiter-
penes may possess antiprotozoal effects (anecdotal).
Antithrombotic effects: Rosmarinic acid has been reported to dem-
onstrate inhibitory effects on both the classical pathway convertase
and the alternative pathway convertase. One study reported that
rosmarinic acid inhibited 70% of the immunohemolysis of anti-
body-coated sheep erythrocytes by guinea pig serum via possible
inhibition of the C3 convertase of the classical complement path-
way. However, higher concentrations of rosmarinic acid were less
effective.73 Rosmarinic acid was also reported to inhibit C5 con-
vertase in the classical pathway.73,93
Antithyroid effects: Studies have shown that freeze-dried extracts
of lemon balm were reported to inhibit the binding of bovine TSH
to human thyroid plasma membranes and adenylate cyclase. In rat
liver microsomes, lemon balm aqueous extract was reported to in-
hibit the extrathyroidal enzymatic T4-5-deiodination to both T3-
and T4-5-deiodination.31,32 The thyroid-stimulating immuno-
globulin G (IgG) found in patients with Graves’ disease has been
reported to resemble TSH in its ability to bind to the thyroid
plasma membrane and to activate the thyroid gland. Freeze-dried
extracts of lemon balm were reported to exhibit antithyrotropic ac-
tivity by forming adducts with TSH that bound weakly, if at all, to
the TSH receptor. When IgG was incubated with extracts of lemon
balm, a dose-dependent decrease was reported in the TSH-binding
inhibitory activity. As a result of this reported decrease, adenylate
cyclase activity was stimulated (thyroid-stimulating immunoglob-
ulin activity) and thyroid iodine release was enhanced in the
McKenzie assay system. Cinnamic acid has been reported to in-
hibit the binding of TSH to human thyroid membranes.31,32 In
euthyroid rats, the administration of freeze-dried extracts of lemon
balm was reported to reduce pituitary and serum TSH concentra-
Emmenagogic effects: One study suggested that freeze-dried ex-
tracts of lemon balm inhibited binding of 125I hCG to rat testis
membranes.38 In rats, prolactin serum levels and hypophyseal
stores were reported to be reduced by 40 mg/100 grams of a
freeze-dried extract of lemon balm.33
Spasmolytic effects: Due to lack of clinical data, lemon balm has
not been recommended for use as a spasmolytic agent.18-20 Using
histamine and acetylcholine as spasmogens in guinea pig ileum, no
significant antispasmodic activity resulting from lemon balm ex-
tracts were reported.(18) Studies on isolated duodenum of rat have
reported antispasmodic effects of lemon balm in vitro.100
Sedative effects: In mice, an aqueous alcoholic extract of lemon
balm was reported to produce dose-dependent sedation, inducing
sleep and potentiating sub-hypnotic and hypnotic doses of pento-
barbital. On the other hand, in the same study the essential oil of
lemon balm was reported to have no sedative effect.13 With high
doses, a peripheral analgesic effect was noted.13 In tests on Wistar
strain rats and on laboratory mice, lemon balm dried extract was re-
ported to exert influence on CNS in evoking antiaggressive activity.
CNS studies of rat reported sedative, hypnotic, and analgesic effects
of lemon balm in vivo.100 An ethanolic extract of lemon balm was
tested for affinity to the GABA(A)-benzodiazepine site, and moder-
ate activity was reported.101 However, a study of a volatile oil-free
hydroalcoholic extract reported sedative activity in mice.
Cardiovascular effects: One study demonstrated that aqueous ex-
tracts of lemon balm provoked a significant reduction in the car-
diac rate in isolated rat hearts, while the contractile force remained
unchanged. This was reported to be caused by the stimulation of
cardiac muscarinic receptors.102
Insufficient available data.
Lemon balm is a delicate, low-growing (1-2 foot) perennial herb
with lemon-smelling, pointed, heart-shaped or oval leaves, and
small white or yellow flowers. The leaves are used medicinally.
Natural Standard Review 87
Lemon balm is native to the Mediterranean region, and now is also
grown in western Asia, the United States, and Europe.
Lemon balm is commonly planted in gardens to attract bees. The
name comes from the Greek word “melissa” which means “bee,”
and “balm,” a short form of “balsam.” The medicinal use of lemon
balm has been documented since Ancient Greek and Roman times.
Refers to the medical condition or disease targeted by a therapy.
Study Design
Common types include:
Randomized controlled trial (RCT): An experimental trial in which
participants are assigned randomly to receive either an interven-
tion being tested or placebo. Note that Natural Standard defines
RCTs as being placebo-controlled, while studies using active con-
trols are classified as equivalence trials (see below). In RCTs, par-
ticipants and researchers are often blinded (i.e., unaware of group
assignments), although unblinded and quasi-blinded RCTs are
also often performed. True random allocation to trial arms, proper
blinding, and sufficient sample size are the basis for an adequate
Equivalence trial: An RCT which compares two active agents.
Equivalence trials often compare new treatments to usual (stan-
dard) care, and may not include a placebo arm.
Before and after comparison: A study that reports only the change
in outcome in each group of a study, and does not report be-
tween-group comparisons. This is a common error in studies that
claim to be RCTs.
Case series: A description of a group of patients with a condition,
treatment, or outcome (e.g., 20 patients with migraine headache
underwent acupuncture and 17 reported feeling better afterwards).
Case series are considered weak evidence of efficacy.
Case-control study: A study in which patients with a certain out-
come are selected and compared to similar patients (without the
outcome) to see if certain risk factors/predictors are more common
in patients with that outcome. This study design is not common in
the complementary & alternative medicine literature.
Cohort study: A study which assembles a group of patients with
certain baseline characteristics (for example, use of a drug), and fol-
lows them forward in time for outcomes. This study design is not
common in the complementary & alternative medicine literature.
Meta-analysis: A pooling of multiple trials to increase statistical
power (often used to pool data from a number of RCTs with small
sample sizes, none which demonstrates significance alone but in
aggregate can achieve significance). Multiple difficulties are en-
countered when designing/reviewing these analyses; in particular,
outcomes measures or therapies may differ from study to study,
hindering direct comparison.
Review: An author’s description of his or her opinion based on per-
sonal, non-systematic review of the evidence.
Systematic review: A review conducted according to pre-specified
criteria in an attempt to limit bias from the investigators. System-
atic reviews often include a meta-analysis of data from the in-
cluded studies.
Author, Year
Identifies the study being described in a row of the table.
The total number of subjects included in a study (treatment group
plus placebo group). Some studies recruit a larger number of subjects
initially, but do not use them all because they do not meet the study’s en-
try criteria. In this case, it is the second, smaller number that qualifies as
N. N includes all subjects that are part of a study at the start date, even if
they drop out, are lost to follow-up, or are deemed unsuitable for analy-
sis by the authors. Trials with a large number of drop-outs that are not
included in the analysis are considered to be weaker evidence for effi-
cacy. (For systematic reviews the number of studies included is re-
ported. For meta-analyses, the number of total subjects included in the
analysis or the number of studies may be reported.)
Statistically Significant?
Results are noted as being statistically significant if a study’s authors
report statistical significance, or if quantitative evidence of significance
is present (such as p values).
Natural Standard Review 89
Quality of Study
A numerical score between 0-5 is assigned as a rough measure of
study design/reporting quality (0 being weakest and 5 being strongest).
This number is based on a well-established, validated scale developed
by Jadad et al. (Jadad AR, Moore RA, Carroll D, et al. Assessing the
quality of reports of randomized clinical trials: Is blinding necessary?
Controlled Clinical Trials 1996;17[1]:1-12). This calculation does not
account for all study elements that may be used to assess quality (other
aspects of study design/reporting are addressed in the “Evidence Discus-
sion sections of reviews).
A Jadad score is calculated using the seven items in the table be-
low. The first five items are indications of good quality, and
each counts as one point towards an overall quality score. The
final two items indicate poor quality, and a point is subtracted
for each if its criteria are met. The range of possible scores is 0
to 5.
Magnitude of Benefit
This summarizes how strong a benefit is: small, medium, large, or
none. If results are not statistically significant “NA” for “not applica-
ble” is entered. In order to be consistent in defining small, medium, and
large benefits across different studies and reviews, Natural Standard de-
fines the magnitude of benefit in terms of the standard deviation (SD) of
the outcome measure. Specifically, the benefit is considered:
Jadad Score Calculation
Item Score
Was the study described as randomized (this includes words such as randomly, random, and
Was the method used to generate the sequence of randomization described and appropriate (table of
random numbers, computer-generated, etc)?
Was the study described as double blind? 0/1
Was the method of double blinding described and appropriate (identical placebo, active placebo, dummy,
Was there a description of withdrawals and dropouts? 0/1
Deduct one point if the method used to generate the sequence of randomization was described and it was
inappropriate (patients were allocated alternately, or according to date of birth, hospital number, etc).
Deduct one point if the study was described as double blind but the method of blinding was inappropriate
(e.g., comparison of tablet vs. injection with no double dummy). 0/1
Large: if > 1 SD;
Medium: if 0.5 to 0.9 SD;
Small: if 0.2 to 0.4 SD.
In many cases, studies do not report the standard deviation of change
of the outcome measure. However, the change in the standard deviation
of the outcome measure (also known as effect size) can be calculated,
and is derived by subtracting the mean (or mean difference) in the pla-
cebo/control group from the mean (or mean difference) in the treatment
group, and dividing that quantity by the pooled standard deviation (Ef-
fect size = [Mean Treatment Mean Placebo]/SDp).
Absolute Risk Reduction
This describes the difference between the percent of people in the
control/placebo group experiencing a specific outcome (control event
rate), and the percent of people in the experimental/therapy group expe-
riencing that same outcome (experimental event rate). Mathematically,
absolute risk reduction (ARR) equals experimental event rate minus
control event rate. ARR is better able to discriminate between large and
small treatment effects than relative risk reduction (RRR), a calculation
that is often cited in studies [(control event rate experimental event
rate/control event rate)]. Many studies do not include adequate data to
calculate the ARR, in which cases “NA” is entered into this column.
Number Needed to Treat
This is the number of patients who would need to use the therapy un-
der investigation, for the period of time described in the study, in order
for one person to experience the specified benefit. It is calculated by di-
viding the absolute risk reduction into 1 (1/ARR).
When appropriate, this brief section may comment on design flaws
(inadequately described subjects, lack of blinding, brief follow-up, not
intention-to treat, etc.), notable study design elements (crossover, etc.),
dosing, and/or specifics of study group/sub-groups (age, gender, etc.).
More detailed description of studies is found in the “Evidence Discus-
sion” section that follows the “Evidence Table” in Natural Standard
Natural Standard Review 91
Herpes Simplex Virus Infections
Summary: Rigorous clinical data are lacking. Preliminary clinical
studies demonstrate promising effects. See Tables 3 and 4.
Evidence: Vogt et al. investigated the efficacy of a cream contain-
ing lemon balm extract in a randomized, placebo controlled, dou-
ble-blind trial in 116 patients with Herpes simplex infections.103
Patients were treated with either Lomaherpan Creme or placebo
two to four times per day over a period of up to 10 days. Symptoms
were documented after day two and at the end of the treatment pe-
riod (average five days). Symptoms investigated were reddening,
swelling, blisters, erosions, scab, pain, and healing. Severity of
symptoms was expressed in a score from one to four. Overall eval-
uation used a score from one to five. Regression of reddening and
reduction of swelling were reported as statistically significant vs.
placebo. Overall evaluation of efficacy was reported as signifi-
cantly positive vs. placebo both by patients and doctors. The au-
thors suggested that Lomaherpan proved effective in the treatment
of Herpes simplex infections. Efficacy was greater, the earlier treat-
ment commenced.
A placebo controlled, double-blind trial was conducted to evaluate
the efficacy of lemon balm in the treatment of herpes simplex skin
or mucosa infections in 116 patients.24 To be included into the trial,
patients must have had symptoms for no more than 72 hours, could
have either skin or transitional mucosa infections, and could not be
on any antiviral treatment. Patients could apply placebo or topical
Lomahephan®(1% dried lemon balm extract) 2-4 times per day for
5-10 days. Outcome measures assessed redness, swelling, scabs,
pain, healing, and vesicles on a one to four point symptom scale,
lesion size, and efficacy (globally assessed by patients and physi-
cians). Results reported that at day two, redness and swelling were
significantly improved in the lemon balm group (p = 0.0055 and
p = 0.25, respectively) compared to the placebo group. Global as-
sessment of efficacy by patients (“very good” rating 24 times in
the treatment group vs. 11 times in the placebo group, p = 0.022)
and physicians (“very good” rating in 25 times in the treatment
group and 10 times in the placebo group, p = 0.031) were reported
as significantly higher in the lemon balm group vs. the placebo
group. Reported side effects included irritation in one patient tak-
ing lemon balm and in two patients taking placebo. Two patients
taking placebo also reported a burning sensation. Subgroup analy-
sis of 67 patients demonstrated a quicker decrease in lesion area in
the lemon balm group, which was not significant on day two but
was significant on day five (p = 0.012). One limitation of this trial
is the flexibility in dosing regimen.
Koytchev et al. conducted a randomized, placebo controlled, dou-
ble-blind trial to examine the effects of lemon balm in 66 patients
with a history of recurrent herpes labialis.22 Patients must have ex-
perienced at least four episodes per year to be included in the
study. Patients received either placebo or Lomaherpan®(1% cream
of freeze-dried lemon balm extract) and were treated topically on
the affected area four times per day for five days. The patients
were instructed to start the application within four hours of symp-
toms and return for a physician visit within 24 hours. Symptoms
including bother, number of blisters, and size of affected area were
scored on a scale developed for acyclovir trials. The primary out-
come measure was a symptom score on day two, and secondary
endpoints included total scores of symptoms over five days of
treatment. Results revealed a symptom score on day two of 4.03 in
the lemon balm group vs. 4.94 in the placebo group (p = 0.042).
According to the authors, the difference between total scores was
not significant (p = 0.16). Physician assessment was also reported
as not significant. Limitations include lack of reporting of side ef-
fects and tolerance of treatment.
A case series was conducted to study the efficacy of lemon balm in
the treatment of 115 patients with cold sores. To be included on the
study, patients experienced symptoms for less than 72 hours.
Cream containing 1% dried lemon balm extract was applied to ar-
eas of herpes simplex infection as needed up to five times per day,
up to 14 days.23,24 The primary endpoint was the complete healing
of the lesion. Healing was completed in 60% of the patients by day
four, 87% by day six, and 96% by day eight. According to the au-
thors, these results suggested that the benefit from using lemon
balm was dubious. The effect attributed to lemon balm was re-
ported as no shorter than that of the natural course of the disease.
The rate of adverse effects was 2.6% (three patients) and included
reddening of the skin, burning sensation, paresthesia, and in one
case, residual pigmentation. This study is limited by its lack of a
placebo control group.
Natural Standard Review 93
TABLE 3. Evidence Table
Condition Study
N Statistically
Quality of
0-2 = poor
3-4 = good
5 = excellent
of Benefit
ARR NNT Comments
116 Yes 4 Medium 26% 4 Cream with
1% lemon
balm (70:1)
used bid to
qid x 10
days. Side
effects less
than 1%;
116 Yes 3 Small 24.9% 4 Cream with
1% lemon
balm (70:1)
used bid to
qid x 5-10
66 No 2 NA NA NA Cream with
1% lemon
balm (70:1)
applied within
4 hours of
then qid x 5
Case series Wölbling,
115 No 1 NA NA NA Cream with
1% lemon
balm used 5
times per day
x 14 days.
No placebo
control group.
Agitation in
Ballard, 2002 72 Yes 3 Small Reduction
in Cohen-
(CMAI): 24%
4 Lotion with
lemon balm
applied to
patients’ face
and arms bid.
Anxiety Randomized,
102 Yes 4 NA NA NA Combination
product used
at 0.23 mL/kg
body weight.
Anxiety Case series Lagoni,
92 NA 2 NA NA NA Combination
product used.
Anxiety Case series Schmidt,
1599 NA 2 NA NA NA Combination
product used.
1395 patients
42 Yes 3 Small NA NA Lemon balm
extract used
at 60 drops/
48 Yes 2 Small NA NC 2 tablets of
product used.
Natural Standard Review 95
Condition Study
Author, Year N Statistically
Quality of
0-2 = poor
3-4 = good
5 = excellent
of Benefit
ARR NNT Comments
and mood
20 NA 2 NA NA NA 3 00, 600, and
900mg of
extract used
20 NA 2 NA NA NA 600, 1000,
and 1600mg
dried leaf
used at 7-
day intervals
by healthy
Dyspepsia Multicenter,
120 Yes 3 Medium Relief from
2.5 Combination
Dyspepsia Double-blind,
60 Yes 3 Medium NA NA Combination
Dyspepsia Multicenter
case series
152 NA 1 NA NA NA Combination
product used.
Sleep quality,
98 No 4 NA 23.9% 4 Healthy
three tablets
qd, half-hour
Sleep quality Randomized,
68 Yes 3 Medium 40% overall
3 Combination
Sleep quality Randomized,
27 Yes 2 Small NA NA Combination
used, short
Sleep quality,
mild to
50 Yes 2 Medium NA NA Combination
Sleep quality Controlled,
20 Yes 1 NA NA NA Healthy
product; not
Sleep quality Case series Orth-Wagner,
225 Yes 1 NA NA NA Combination
Agitation in Dementia
Summary: Limited data are available supporting the use of lemon
balm as a treatment of agitation in dementia patients. Additional
study is necessary before a conclusion can be drawn. See Table 3.
Evidence: Ballard et al. conducted a randomized, placebo con-
trolled, double-blind trial to determine the value of aromatherapy
with essential oil of lemon balm for agitation in 72 patients with
severe dementia.39 Patients with clinically significant agitation in
the context of severe dementia were included in the study. Lotion
enriched with either lemon balm essential oil or placebo oil was
applied to patients’ faces and arms twice per day. Measurements of
effectiveness included agitation [Cohen-Mansfield Agitation In-
ventory (CMAI)] and quality of life indices (percentage of time
spent socially withdrawn and percentage of time engaged in con-
structive activities, measured with Dementia Care Mapping). Sixty
percent of the active treatment group and 14% of the placebo-
treated group reported a 30% reduction of CMAI score, with an
overall improvement in agitation (mean reduction in CMAI score)
of 35% in patients receiving lemon balm essential oil and 11% in
those treated with placebo. Quality of life indices were also re-
ported to improve significantly more in patients receiving the ac-
tive treatment. No significant side effects were reported. Although
the results of this trial are promising, this trial is limited due to a
small sample size.
Summary: Preliminary human evidence has been published that
supports the use of lemon balm for anxiety, commonly referred to
in the literature as psycho-vegetative disturbances. Further re-
search is needed to confirm these results. See Table 3.
TABLE 4. Explanation of Columns in Natural Standard Evidence Table
12345 6 78910
Condition Study
N Statistically
Quality of
0-2 = poor
3-4 = good
5 = excellent
of Benefit
Needed to
Evidence: Büchner et al. conducted a randomized, placebo con-
trolled, double-blind trial to examine the efficacy of lemon balm in
102 patients with anxiety and somatic complaints.37 Subjects were
assigned to take either placebo or Klosterfrau Melissengeist®at a
dose of 0.23 mL/kg body weight three times per day for eight
weeks. Outcome measures included psychological tests, which
were taken before and during the eight-week trial. Results reported
a significant improvement of the clinical state, including improve-
ments in symptoms of “vegetative disturbances,” including “inner
restlessness,” blushing, palpitation, and headache (p < 0.05). The
PF 16 Cattell test demonstrated a significant difference for dimen-
sion C = Ego Strength vs. Ego Weakness (p < 0.05). Significant
differences between the experimental and the control groups were
also reported in the FPI test for the dimensions of nervousness (p <
0.01) and excitability (p < 0.02). The FPI dimension of emotional
lability also demonstrated significant differences between the two
groups (p < 0.05). Pronounced effects were reported in female sub-
jects (p < 0.01). Eight patients in the treatment group reported side
effects including slight nausea, diarrhea, headache, and palpita-
tions, and five patients in the placebo group reported nausea, diar-
rhea, and headache. The major limitation of this trial is that it
assessed the efficacy of a combination product. Further random-
ized, controlled trials assessing lemon balm monotherapy are war-
In a multicenter, four-week study involving 92 patients, the herbal
compound Seda-Plantinag was tested as an alternative to prescrip-
tion sedatives.104 According to the study results, Seda-Plantinag did
not lead to any signs of fatigue during the day. Patients reported a
clear decrease in the degree of their states of agitation or excite-
ment, as well as improvements with regard to their power of con-
centration and social efficiency. The authors suggested that a
combination of single herbal agents with sedative, psychotropic
effects proved to be well tolerated and may serve as an alternative
for synthetic tranquillizers, even if prescribed regularly in the
In a large case series, 1599 patients with symptoms of anxiety
were treated with Euvegal coated tablets (a combination product
with Valeriana officinalis and lemon balm).105 Patients reporting
nervousness, fatigue, and sleep disturbances were included in the
study. Patients were given one to two tablets of Euvegal twice per
day over a four-week period. After week two and week four, sever-
Natural Standard Review 97
ity of symptoms and possible adverse effects were documented. A
total of 1395 patients completed the observation. In two-thirds an
almost complete regression of symptoms was observed. Over 90%
of patients reported an improvement. Mild adverse effects were re-
ported in 32 cases. Limitations of this study are that it assessed the
efficacy of a combination product and that it was not a random-
ized, controlled trial.
Cognitive Performance
Summary: Clinical data suggest that the use of standardized lemon
balm extract has some effect on particular self-reported measures
of mood and cognition through cholinergic activities.4,5,14 More
rigorous studies need to be conducted using patient-relevant out-
comes to better assess the validity of these results as they apply to
patient care. See Table 3.
Evidence: Akhondzadeh et al. conducted a randomized, controlled
trial to assess the efficacy and safety of lemon balm extract in 42
patients with Alzheimer’s disease.62 The study included patients
with mild to moderate Alzheimer’s disease. Patients were given a
fixed dose of 60 drops/day of lemon balm extract. The primary
outcome measures were changes in the cognitive subscale of an
Alzheimer’s disease assessment scale and on the clinical dementia
rating. At four months, the results demonstrated that lemon balm
extract produced a significantly better outcome on cognitive func-
tion than placebo. No significant differences in the two groups in
terms of observed side effects were reported, except agitation,
which was more common in the placebo group. The authors sug-
gested that from these results lemon balm may be beneficial in the
treatment of patients with mild to moderate Alzheimer’s disease.
Further research is needed to confirm these results.
In a randomized, placebo controlled, double-blind trial, Herberg et
al. investigated the everyday safety of a Valeriana officinalis-
Humulus lupulus-lemon balm combination in 48 adults aged 30 to
60 years old. Subjects received two tablets (95 mg Valeriana officinalis,
15 mg Humulus lupulus, and 85 mg lemon balm per tablet) or pla-
cebo three times per day for two weeks. Cognitive performance
was assessed using a computerized test battery. The combination
with alcohol (mean 0.5%) was also investigated. No inhibition of
cognitive performance was reported. According to the authors,
statistically significant differences vs. placebo concerned improve-
ment of general well-being and cognitive skills only. No signifi-
cant side effects were reported. The authors reported that the
Valeriana officinalis-Humulus lupulus-lemon balm combination
did not affect the effect of alcohol consumption.
Kennedy et al. conducted a randomized, placebo controlled, dou-
ble-blind, crossover trial to examine effects of three doses of
lemon balm on cognition and mood in 20 participants.35 Partici-
pants received either 300 mg, 600 mg, or 900 mg of a standardized
extract of lemon balm or placebo, on different days, each separated
by a seven-day washout period. Outcome measures included the
cognitive performance as assessed by Cognitive Drug Research
(CDR) computerized test battery and subjective mood rating as as-
sessed by Bond-Lader visual analogue scales. The results demon-
strated a sustained increase in “accuracy of attention” after
ingesting 600 mg and reductions in “secondary memory” and
“working memory” that were time- and dose-dependent. Patients
reported reductions in “alertness” after the administration of 900
mg and reported that “calmness” was elevated after the adminis-
tration of 300 mg. A limitation of this study is the small sample of
young, healthy subjects not representative of the population of pa-
tients with dementia who may benefit from lemon balm.
Kennedy et al. conducted a randomized, placebo controlled, dou-
ble-blind, crossover study which investigated the acute effects on
cognition and mood of a standardized extract of lemon balm in 20
healthy adults.2Participants received single doses of 600 mg, 1000
mg, and 1600 mg of lemon balm (Pharmaton) or a matching pla-
cebo at seven-day intervals. Cognitive performance was assessed
using the Cognitive Drug Research (CDR) computerized test bat-
tery and two serial subtraction tasks. A sustained improvement in
“accuracy of attention” following 600 mg of lemon balm and time-
and dose-specific reductions in both “secondary memory” and
“working memory” factors were demonstrated in the treatment
group. Self-rated “calmness,” as assessed by Bond-Lader mood
scales, was reported to be elevated at the earliest time points by the
lowest dose, and “alertness” was reported to be significantly re-
duced at all time points after the highest dose. A limitation of this
study is the small sample of young, healthy subjects not represen-
tative of the population of patients with dementia who may benefit
from lemon balm.
Natural Standard Review 99
Summary: Limited clinical evidence is available supporting the
use of lemon balm for the treatment of chronic colitis. See Table 3.
Evidence: In a case series, 24 patients with chronic non-specific
colitis were treated with a combination of Taraxacum officinale,
Hypericum perforatum, lemon balm, Calendula officinalis, and
Foeniculum vulgare.106 Primary outcome measures included de-
crease in symptoms. Results demonstrated the disappearance of
spontaneous and palpable pains along the large intestine in 95.83%
of the patients by day 15 of treatment, and daily bowel movements
in the patients with obstipation syndrome. Although these results
are promising, lack of randomized, controlled trials with an ade-
quate sample population prevents meaningful extrapolation of
these results to clinical practice.
Summary: Clinical evidence of varying quality suggests that lemon
balm may help reduce dyspepsia as a component of combination
products. However, further research is necessary before a conclu-
sion can be drawn.
Evidence: Madisch et al. conducted a multicenter, placebo con-
trolled, double-blind trial using the commercially available, herbal
combination preparation Iberogast®, which contains lemon balm,
with and without the ingredient bitter candy tuft in 60 patients with
functional dyspepsia.63 Patients discontinued all medications for
seven days and then received either of the Iberogast®preparations
or a placebo for four weeks. Gastrointestinal symptom (GIS) score
and total scores consisting of ten dyspeptic symptoms rated on a
Likert scale measured at baseline, at week two, and at week four
were reported as statistically significant compared to baseline at p <
0.001. Although the results from this study are promising, it is lim-
ited due to the fact that the preparation studied was a combination
product and the contribution of the lemon balm component to the
effects is not discernable without direct comparisons of each indi-
vidual component.
Madisch et al. conducted a multicenter, randomized, placebo con-
trolled, double-blind trial to assess the efficacy and safety of an
herbal combination product STW 5-II, which contains extracts
from bitter candy tuft, matricaria flower, peppermint leaves, cara-
way, licorice root, and lemon balm, for the treatment of patients
with functional dyspepsia.107 One hundred twenty patients with
functional dyspepsia were randomly assigned to one of four treat-
ment groups. The primary outcome measure was the improvement
of a standardized gastrointestinal symptom (GIS) score. During
the first four weeks, the GIS score was reported to significantly de-
crease in subjects on active treatment compared to those on pla-
cebo. After eight weeks 43.3% on active treatment and 3.3% on
placebo reported complete relief of symptoms. Although the re-
sults from this study are promising, it is limited due to the fact that
the preparation studied was a combination product, and the contri-
bution of the lemon balm component to the effects is not discern-
able without direct comparisons of each individual component.
In a multicenter, open case series, the efficacy of Gastrol S (a com-
bination product containing lemon balm) in the treatment of ner-
vous irritable stomach and dyspepsia was tested in 152 patients.108
A majority (58.5%) of the patients participated in the study for
more than eight weeks. In 65.5% a dosage of 20-25 drops three
times per day was recommended. Tolerance was reported as “good”
by 93.4% of the patients, and the therapy was assessed as “very
good” by 75.5%. In 82.2% of all documented cases, a distinct im-
provement of symptoms was reported. This study is limited due to
the fact that the preparation studied was a combination product and
the contribution of the lemon balm component to the effects is not
discernable without direct comparisons of each individual compo-
Sleep Quality
Summary: High-quality clinical evidence supporting the use of
lemon balm as a sedative/hypnotic is lacking.70 The available evi-
dence is conflicting, of low quality, or derived from early-phase
trials in humans. A systematic review published in 1998 concluded
that the paucity of evidence made the sedative effect of lemon
balm difficult to assess given that studies usually employed com-
bination products, most often with Valeriana officinalis, which it-
self possesses sedative properties.27 Rigorous clinical studies are
required to better support use of lemon balm as a sedative/hyp-
notic. See Table 3.
Evidence: Cerny et al. conducted a multicenter, randomized, pla-
cebo controlled, double-blind study to assess tolerance and effi-
Natural Standard Review 101
cacy of a Valeriana officinalis/lemon balm combination product in
the treatment of minor sleep disorders in 98 healthy volunteers.34
Subjects were randomly assigned to receive placebo or three tab-
lets of a combination product (120 mg Valeriana officinalis, 80 mg
lemon balm) one half-hour before bedtime for 30 days. Outcome
measures included rating scales for tolerability, sleep quality, and
well-being, as well as laboratory and physical parameters. Results
reported a rating of good overall tolerability by 93% of subjects in
the Valeriana officinalis/lemon balm group vs. 91% of subjects in
the placebo group. Incidence of mild adverse effects reported was
28.8% in the Valeriana officinalis/lemon balm group vs. 28.1% in
the placebo group. Among those taking Valeriana officinalis/
lemon balm, 33.3% of patients reported an improvement in sleep
quality vs. 9.4% in the placebo group (p = 0.04). No significant
changes were reported in regard to laboratory tests, physical exam-
ination, or rating of well-being, even though the Valeriana officinalis/
lemon balm group reported a higher quality of sleep compared to
the placebo group. From these results, the authors reported safety
of the Valeriana officinalis/lemon balm combination product and
possible efficacy in improving sleep quality. Though results may
appear to be promising, it is important to note that results reflect
efficacy and safety of a combination product. Further randomized,
controlled trials assessing monotherapy of lemon balm in improv-
ing sleep quality are warranted.
A multi-center, placebo controlled, double-blind trial studied the
therapeutic effect of a high dose standardized Valeriana officinalis-
lemon balm combination (Euvegal forte) on mild insomnia in 68
patients.109 Patients with mild insomnia as defined by the DSM-
3-R and the ICD10 were included in the study. Outcome measures
included quality of sleep, general health, and overall clinical im-
pression. Patients received two tablets twice per day of Euvegal
and were examined after two weeks of treatment. All criteria were
reported as significantly improved vs. placebo. No hangover or re-
bound phenomena were reported.
Lindahl et al. conducted a randomized, double-blind, crossover
trial with 27 subjects with sleep difficulties to assess the effects of
a combination product containing Valeriana officinalis,Flores
humuli, and lemon balm on sleep quality.110 Subjects received the
combination product (400 mg of Valeriana officinalis, 375 mg of
Flores humuli, and 160 mg of lemon balm) or placebo for the first
night and then received the opposite treatment the following night.
Outcome measures including sleep quality were recorded on a pa-
tient questionnaire that was completed on the second morning.
From the results, the authors reported that 21 out of 27 patients
rated the combination product better than placebo. The difference
between ratings of the two preparations was reported as statisti-
cally significant (p < 0.001). In terms of sleep quality, 24 out of 27
subjects reported an improvement, and 12 reported “perfect” sleep.
No side effects were noted. Short study duration limits the clinical
utility of these results. Long-term trials may be more helpful in
evaluating efficacy of a product in sleep disturbances. Longer,
well-designed, randomized, controlled trials assessing the mono-
therapy of lemon balm are warranted.
In a randomized, placebo controlled trial, the sedative effectsof
aValeriana officinalis-Humulus lupulus-lemon balm-Leonurus
cardiaca combination product were examined in 50 male alcohol
abusers with sleep disturbances and other withdrawal symptoms.111
From their evaluation of the results, the authors reported signifi-
cant improvement in sleep quality and significant decrease in sleep
interruption and bad dreams. Morning sleepiness was observed as
a side effect.
Dressing et al. conducted a controlled, double-blind study to as-
sess effects of a Valeriana officinalis/lemon balm preparation on
sleep in 20 healthy volunteers.36 Subjects were divided into
good and poor sleepers. Subjects received either a Valeriana
officinalis/lemon balm preparation (Euvegal Forte®: 160 mg Valeriana
officinalis, 80 mg lemon balm), triazolam (125 mg), or placebo at
bedtime. Outcome measures included sleep efficiency, length,
time in sleep stages, and delta sleep. From the results, the authors
suggested that the use of the Valeriana officinalis/lemon balm
combination product on the poor sleepers induced a significant in-
crease in sleep efficiency and in sleep stages three and four. A sig-
nificant increase in delta sleep in the group of poor sleepers was
also reported. Rebound effects were not reported for groups taking
the Valeriana officinalis/lemon balm preparation or the triazolam.
Limitations to this study include lack of randomization and the use
of a combination product.
In an open, multicenter study of sleep quality, the efficacy and toler-
ance of Novo-Baldriparan, containing Valeriana officinalis,Humulus
lupulus, and lemon balm, was investigated in 225 patients.112 The
study included patients that reported difficulties falling asleep and
Natural Standard Review 103
sleeping through the night and/or states of nervous agitation. The
two-week therapy with this product was reported to yield a signifi-
cant improvement in the severity and frequency of the principal
symptoms. According to the reported results, both the nervous agi-
tation, which was identified as the underlying cause of the sleep
disorders, as well as the sleep disorders themselves were signifi-
cantly reduced. Specifically, the authors reported that the difficul-
ties falling asleep improved in 89% of the patients, the difficulties
sleeping through the night improved in 80%, and the states of ner-
vous agitation improved in 82% of the patients. The quantity of
sleep was reported to increase markedly, while external stressors
were reported as being less distressing. A similar improvement in
the somatic symptoms, like headache, dizziness, cardiovascular,
or gastrointestinal discomfort, was reported. The reduction in
heart rate and blood pressure under therapy was reported to be ac-
companied as a whole by a noticeable improvement in the pa-
tients’ well being. The tolerability of Novo-Baldriparan was rated
positively by both physicians and patients: 96.9% of the physi-
cians and 96.4% of the patients gave the rating “very good” or
“good.” The primary limitation of this study includes the use of a
combination product.
Brands Used in Clinical Trials
Euvegal Forte®(Spitzner, Germany)36,105,109
Iberogast®(Phyto Pharmica, Germany)63
Klosterfrau Melissengeist®(Klosterfrau, Germany)37
Songha Night®(Pharmaton Natural Health Products, Bioggio/
Lugano, Switzerland)34
STW 5-II107
Baldriparan Stark N Beruhigungs-Dragees68
Gastrol S108
United States Patents
6,881,776 Gel compositions
6,831,103 Composition comprising theanine
6,827,944 Percutaneous administration preparations
6,797,284 Phytopharmaceutical food products or integrators
6,780,825 Cleansing compositions with milk protein and aroma-
6,703,022 Composition and method useful for treating colic
6,664,225 Single-dose quick-dissolving cleansing agent with me-
dicinal properties
6,641,801 Gargle method to reduce the duration of common cold
6,629,835 Combinations of diterpene triepoxide lactones and ditepene
lactones or triterpenes for synergistic inhibition of cyclooxygenase-2
6,589,566 Composition comprising theanine
6,509,042 Antiviral composition
6,444,253 Flavor delivery system
6,423,336 Chewing gums and method of manufacturing the same
6,416,769 Cosmetic compositions comprising exfoliating enzymes
and uses thereof
6,405,948 Liberating intracellular matter from biological material
6,346,250 Composition and method useful for treating colic
6,342,208 Oil-in-water emulsion containing C10-C24 fatty acid
derivatives for treating skin of mammals
6,210,738 Freeze-dried ginseng berry tea
6,165,964 Aqueous solution of essential oil, and antimicrobial
agents, microbicides and antimicrobial finishes for washing
6,060,061 Method for preventing or treating disorders involving
an inflammatory process
6,024,998 Process for the removal of undesired lipophilic contam-
inations and/or residues, which are contained in beverages or in
vegetable preparations
5,958,499 Fluidized fat
5,906,848 Process for the removal of undesired contaminations
and/or residues contained in beverages or in vegetable preparation
5,869,340 Plant clones containing elevated secondary metabolite
5,720,962 Analgesic lotion for hemorrhoids and method of mak-
ing such lotion
Natural Standard Review 105
5,472,699 Composition and method for visibly reducing the size
of skin pores
5,415,861 Composition and method for visibly reducing the size
of skin pores
5,399,353 Preparations for covering undamaged and/or damaged
areas of human or animal skin
5,318,503 Method and apparatus for auditory and olfactory relax-
5,176,913 Process for preparing a partial extract containing the
volatile in steam components and further lipophilic components of
medical plants and/or spice plants
5,064,675 Herbal extract composition
4,933,177 Cosmetic compositions for the treatment of the hair
and skin contain in the form of powder particles resulting from
the pulverization of at least one plant substance and a cohesion
4,767,618 Cosmetic compositions for the treatment of the hair and
skin in the form of powder particles resulting from the pulveriza-
tion of at least one plant substance and a cohesion agent
4,569,839 Cosmetic compositions for the treatment of the hair and
skin in the form of powder particles resulting from the pulveriza-
tion of at least one plant substance and a cohesion agent
4,358,442 Rosmarinic acid-phospholipide-complex
4,354,035 Process for isolating rosmarinic acid from plants
4,329,361 Use of rosmarinic acid in the treatment of inflamma-
tions and pharmaceutical products used therein
Last Updated: August 2005.
Authors/Editors: Thomas Brendler, BA (PlantaPhile, Berlin);
Joerg Gruenwald, PhD (Phytopharm Consulting); Benjamin
Kligler, MD, MPH (Continuum Center for Health and Heal-
ing); David Keifer, MD (University of Arizona); Tracee Rae
Abrams, PharmD (University of Rhode Island); Jen Woods,
BS (Northeastern University); Heather Boon, BScPhm, PhD
(University of Toronto); Catherine DeFranco Kirkwood, MPH,
CCCJS-MAC (MD Anderson Cancer Center); Ethan Basch,
MD (Memorial Sloan-Kettering Cancer Center); Hope J. Lafferty,
AM (Memorial Sloan-Kettering Cancer Center); Catherine
Ulbricht, PharmD (Massachusetts General Hospital), Dana A.
Hackman, BS (c) (Northeastern University).
Blinded Peer-Review: Natural Standard Editorial Board.
1. Coleta, M., Campos, M. G., Cotrim, M. D., and Proenca, da Cunha. Compara-
tive evaluation of Melissa officinalis L., Tilia europaea L., Passiflora edulis Sims. and
Hypericum perforatum L. in the elevated plus maze anxiety test. Pharmacopsychiatry
2001;34 Suppl 1:S20-S21.
2. Kennedy, D. O., Wake, G., Savelev, S., Tildesley, N. T., Perry, E. K., Wesnes,
K. A., and Scholey, A. B. Modulation of mood and cognitive performance following
acute administration of single doses of Melissa officinalis (Lemon balm) with human
CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology
3. Kennedy, D. O., Little, W., and Scholey, A. B. Attenuation of laboratory-in-
duced stress in humans after acute administration of Melissa officinalis (Lemon Balm).
Psychosom. Med. 2004;66(4):607-613.
4. Perry, E. K., Pickering, A. T., Wang, W. W., Houghton, P., and Perry, N. S. Me-
dicinal plants and Alzheimer’s disease: Integrating ethnobotanical and contemporary
scientific evidence. J. Altern. Complement Med. 1998;4(4):419-428.
5. Perry, E. K., Pickering, A. T., Wang, W. W., Houghton, P. J., and Perry, N. S.
Medicinal plants and Alzheimer’s disease: From ethnobotany to phytotherapy. J.
Pharm. Pharmacol. 1999;51(5):527-534.
6. Ramos, Ruiz A., De la Torre, R. A., Alonso, N., Villaescusa, A., Betancourt, J.,
and Vizoso, A. Screening of medicinal plants for induction of somatic segregation ac-
tivity in Aspergillus nidulans. J. Ethnopharmacol. 7-5-1996;52(3):123-127.
7. Herrmann, E. C., Jr. and Kucera, L. S. Antiviral substances in plants of the mint
family (Labiatae). II. Nontannin polyphenol of Melissa officinalis. Proc. Soc. Exp.
Biol. Med. 1967;124(3):869-874.
8. Hohmann, J., Zupko, I., Redei, D., Csanyi, M., Falkay, G., Mathe, I., and
Janicsak, G. Protective effects of the aerial parts of Salvia officinalis,Melissa officinalis
and Lavandula angustifolia and their constituents against enzyme-dependent and en-
zyme-independent lipid peroxidation. Planta. Med. 1999;65(6):576-578.
9. Kucera, L. S. and Herrmann, E. C., Jr. Antiviral substances in plants of the mint
family (Labiatae). I. Tannin of Melissa officinalis. Proc. Soc. Exp. Biol. Med. 1967;
124(3): 865-869.
10. Lamaison, J. L., Petitjean-Freytet, C., and Carnat, A. [Medicinal Lamiaceae
with antioxidant properties, a potential source of rosmarinic acid]. Pharm. Acta Helv.
11. Triantaphyllou, K., Blekas, G., and Boskou, D. Antioxidative properties of wa-
ter extracts obtained from herbs of the species Lamiaceae. Int. J. Food Sci. Nutr. 2001;
Natural Standard Review 107
12. Dragland, S., Senoo, H., Wake, K., Holte, K., and Blomhoff, R. Several culinary
and medicinal herbs are important sources of dietary antioxidants. J. Nutr. 2003;
13. Soulimani, R., Fleurentin, J., Mortier, F., Misslin, R., Derrieu, G., and Pelt, J. M.
Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse.
Planta. Med. 1991;57(2):105-109.
14. Wake, G., Court, J., Pickering, A., Lewis, R., Wilkins, R., and Perry, E. CNS
acetylcholine receptor activity in European medicinal plants traditionally used to im-
prove failing memory. J. Ethnopharmacol. 2000;69(2):105-114.
15. Sadraei, H., Ghannadi, A., and Malekshahi, K. Relaxant effect of essential oil of
Melissa officinalis and citral on rat ileum contractions. Fitoterapia 2003;74(5): 445-452.
16. Farnsworth, N. R., Bingel, A. S., Cordell, G. A., Crane, F. A., and Fong, H. H.
Potential value of plants as sources of new antifertility agents I. J. Pharm. Sci. 1975;
17. Khayyal, M. T., el Ghazaly, M. A., Kenawy, S. A., Seif-el-Nasr, M., Mahran, L.
G., Kafafi, Y. A., and Okpanyi, S. N. Antiulcerogenic effect of some gastrointestinally
acting plant extracts and their combination. Arzneimittelforschung 2001;51(7): 545-553.
18. Forster, H. B., Niklas, H., and Lutz, S. Antispasmodic effects of some medicinal
plants. Planta. Med. 1980;40(4):309-319.
19. Israel, D. and Youngkin, E. Q. Herbal therapies for perimenopausal and meno-
pausal complaints. Pharmacotherapy 1997;17(5):970-984.
20. Kennedy, D. O., Scholey, A. B., Tildesley, N. T., Perry, E. K., and Wesnes, K.
A. Modulation of mood and cognitive performance following acute administration of
Melissa officinalis (lemon balm). Pharmacol. Biochem. Behav. 2002;72(4):953-964.
21. Kucera, L. S., Cohen, R. A., and Herrmann, E. C., Jr. Antiviral activities of ex-
tracts of the lemon balm plant. Ann N.Y. Acad. Sci. 7-30-1965;130(1):474-482.
22. Koytchev, R., Alken, R. G., and Dundarov, S. Balm mint extract (Lo-701) for
topical treatment of recurring herpes labialis. Phytomedicine 1999;6(4):225-230.
23. Wolbling, R. H. and Milbradt, R. [Clinical manifestations and treatment of Her-
pes simplex infections]. Therapiewoche 1984;34:1193-1200.
24. Wolbling, R. H. and Leonhardt, K. Local therapy of herpes simplex with dried
extract from Melissa officinalis. Phytomedicine 1994;1:25-31.
25. May, G. and Willuhn, G. [Antiviral effect of aqueous plant extracts in tissue cul-
ture]. Arzneimittelforschung 1978;28(1):1-7.
26. Yamasaki, K., Nakano, M., Kawahata, T., Mori, H., Otake, T., Ueba, N., Oishi,
I., Inami, R., Yamane, M., Nakamura, M., Murata, H., and Nakanishi, T. Anti-HIV-1
activity of herbs in Labiatae. Biol. Pharm. Bull. 1998;21(8):829-833.
27. Wong, A. H., Smith, M., and Boon, H. S. Herbal remedies in psychiatric prac-
tice. Arch. Gen. Psychiatry 1998;55(11):1033-1044.
28. Berdonces, J. L. [Attention deficit and infantile hyperactivity]. Rev. Enferm.
29. Galasinski, W., Chlabicz, J., Paszkiewicz-Gadek, A., Marcinkiewicz, C., and
Gindzienski, A. The substances of plant origin that inhibit protein biosynthesis. Acta
Pol. Pharm. 1996;53(5):311-318.
30. Chlabicz, J. and Galasinski, W. The components of Melissa officinalis L. that
influence protein biosynthesis in-vitro. J. Pharm. Pharmacol. 1986;38(11):791-794.
31. Auf’mkolk, M., Ingbar, J. C., Kubota, K., Amir, S. M., and Ingbar, S. H. Ex-
tracts and auto-oxidized constituents of certain plants inhibit the receptor-binding and
the biological activity of Graves’ immunoglobulins. Endocrinology 1985;116(5):
32. Auf’mkolk, M., Ingbar, J. C., Amir, S. M., Winterhoff, H., Sourgens, H., Hesch,
R. D., and Ingbar, S. H. Inhibition by certain plant extracts of the binding and adenylate
cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endo-
crinology 1984;115(2):527-534.
33. Sourgens, H., Winterhoff, H., Gumbinger, H. G., and Kemper, F. H. Antihor-
monal effects of plant extracts. TSH- and prolactin-suppressing properties of Litho-
spermum officinale and other plants. Planta Med. 1982;45(2):78-86.
34. Cerny, A. S. and Schmid, K. Tolerability and efficacy of valerian/lemon balm in
healthy volunteers; a double-blind placebo-controlled, multicentre study. Fitoterapia
35. Kennedy, D., Scholey, A., Tildesley, N., and Wesnes, K. Dose-dependent
changes in mood and cognitive performance following single doses of Melissa officinalis
(Lemon Balm) to healthy young adults. Proceedings of the British Psychological Soci-
ety 2001;9(2):209.
36. Dressing, H. Valerian combination therapy vs. benzodiazepine: Same efficacy
in the treatment of sleeping disorders? Therapiewoche 1992;42(12):726-736.
37. Buchner, K.H., Hellings, H., Huber, M., Peukert, E., Spath, L., and Deininger,
R. [Double blind study as evidence of the therapeutic effect of Melissengeist on psy-
cho-vegetative syndromes]. Medizinische Klinik 1974;69(23):1032-1036.
38. Auf’mkolk, M., Kohrle, J., Gumbinger, H., Winterhoff, H., and Hesch, R. D.
Antihormonal effects of plant extracts: Iodothyronine deiodinase of rat liver is inhib-
ited by extracts and secondary metabolites of plants. Horm. Metab. Res. 1984;16(4):
39. Ballard, C. G., O’Brien, J. T., Reichelt, K., and Perry, E. K. Aromatherapy as a
safe and effective treatment for the management of agitation in severe dementia: The
results of a double-blind, placebo-controlled trial with Melissa. J. Clin. Psychiatry
40. Patora, J., Majda, T., Gora, J., and Klimek, B. Variability in the content and
composition of essential oil from lemon balm (Melissa officinalis L.) cultivated in Po-
land. Acta Pol. Pharm. 2003;60(5):395-400.
41. Adzet, T., Ponz, R., and Schulte E. Genetic variability of the essential oil con-
tent of Melissa officinalis. 1992;58:558-561.
42. Adzet, T., Ponz, R., Wolf, E., and Schulte, E. Content and composition of M.
officinalis oil in relation to leaf position and harvest time. 1992;58:562-564.
43. Baerheim-Svendsen, A. and Merkx, IJ. A simple method for screening of fresh
plant material for glycosidic bound volatile compounds. 1989;55:38-40.
44. Hose, S., Zänglein, A., Berg, T. van den, Schultze, W., Kubeczka, K. H., and
Czygan, F. C. Die Pharmazie. Im. Druck. Ontogenetic variation of the essential leaf oil
of Melissa officinalis L. 1997; 52(3):247-253.
Natural Standard Review 109
45. Mrlianova, M., Tekel’ova, D., Felklova, M., Reinohl, V., and Toth, J. The influ-
ence of the harvest cut height on the quality of the herbal drugs Melissae folium and
Melissae herba. Planta Med. 2002;68(2):178-180.
46. Mrlianova, M., Tekel’ova, D., Felklova, M., Toth, J., Musil, P., and Grancai, D.
[Comparison of the quality of Melissa officinalis L. cultivar Citra with Mellissas of Eu-
ropean origin]. Ceska. Slov. Farm. 2001;50(6):299-302.
47. Vaverkova, S., Holla, M., and Takel, J. [The content and quality of Melissa
officinalis essential oil after application of Rastim 30 DKV]. Ceska. Slov. Farm.
48. Patora, J. and Klimek, B. Flavonoids from lemon balm (Melissa officinalis L.,
Lamiaceae). Acta Pol. Pharm. 2002;59(2):139-143.
49. Ziakova, A., Brandsteterova, E., and Blahova, E. Matrix solid-phase dispersion
for the liquid chromatographic determination of phenolic acids in Melissa officinalis.J
Chromatogr. A 1-3-2003;983(1-2):271-275.
50. Araujo, C., Sousa, M. J., Ferreira, M. F., and Leao, C. Activity of essential oils
from Mediterranean Lamiaceae species against food spoilage yeasts. J. Food Prot.
2003; 66(4):625-632.
51. Dimitrova, Z., Dimov, B., Manolova, N., Pancheva, S., Ilieva, D., and Shishkov,
S. Antiherpes effect of Melissa officinalis L. extracts. Acta Microbiol Bulg. 1993;
52. Heitz, A., Carnat, A., Fraisse, D., Carnat, A. P., and Lamaison, J. L. Luteolin
3’-glucuronide, the major flavonoid from Melissa officinalis subsp. officinalis. Fito-
terapia 2000;71(2):201-202.
53. Palma, S. D., Manzo, R. H., and Allemandi, D. A. Dry plant extracts loaded on
fumed silica for direct compression: Preparation and preformulation. Pharm. Dev.
Technol. 1999;4(4):523-530.
54. Hener, U., Faulhaber, S., Kreis, P., and Mosandl, A. On the authenticity evalua-
tion of balm oil (Melissa officinalis L.). 1995;50:60-62.
55. Schultze, W., König, W.A., Hilkert, A., and Richter, R. Melissenöle/Unter-
suchungen zur Echtheit mittels enantioselektiver Gaschromatographie und Isotopen-
verhältnis- Massenspektrometrie. 1995;135:557, 563 567, 571, 577-557, 564, 568,
574, 577.
56. Schultze, W., Zänglein, A., Klose, R., and Kubeczka, K. H. Die Melisse/
Dünnschichtchromatographische Untersuchung des ätherischen Öles. 1989;129: 155-163.
57. Tabatabai, A. S., Buchbauer, G., Jirovetz, L., and Nikiforov, A. Vergleichende
Untersuchungen verschiedener Proben von Melissen-und Citronell-Ölen mittels GC-FID
und GC-FTIR-MS sowie Multivar Datenanalayse. 1995;63(4):352.
58. Wolf, J. Melissenblatter/Mikro-Dunnschichtchromatographie. 1996;141(25):
59. Tekel, J., Vaverkova, S., Kovacicova, J., Hola, M., and Havranek, E. A screen-
ing method for the determination of the residues of uracil herbicides in Melissa
officinalis L. 1994;49(899):901.
60. Berg, T. van den, Freundl, E., and Czygan, F. C. Melissa officinalis ssp.
altissima: Characteristics of a possible adulteration of lemon balm. 1997;52(10):
61. Nakashima, M. J. and Glaze, L. E. Extraction of light filth from whole leaves of
alfalfa, lemon balm, papaya, and spearmint: collaborative study. J. Assoc. Off. Anal.
Chem. 1987;70(6):997-999.
62. Akhondzadeh, S., Noroozian, M., Mohammadi, M., Ohadinia, S., Jamshidi, A.
H., and Khani, M. Melissa officinalis extract in the treatment of patients with mild to
moderate Alzheimer’s disease: A double blind, randomised, placebo controlled trial. J.
Neurol. Neurosurg. Psychiatry 2003;74(7):863-866.
63. Madisch, A., Melderis, H., Mayr, G., Sassin, I., and Hotz, J. [A plant extract and
its modified preparation in functional dyspepsia. Results of a double-blind placebo
controlled comparative study]. Z Gastroenterol. 2001;39(7):511-517.
64. Ward, N. I. and Savage, J. M. Metal dispersion and transportational activities
using food crops as biomonitors. Sci. Total Environ. 5-23-1994;146-147:309-319.
65. West, I. and Maibach, H. I. Contact urticaria syndrome from multiple cosmetic
components. Contact Dermatitis 1995;32(2):121.
66. Hausen, B. M. and Schulze, R. [Comparative studies of the sensitizing capacity
of drugs used in herpes simplex]. Derm Beruf. Umwelt. 1986;34(6):163-170.
67. Schulz, H., Jobert, M., and Hubner, W. D. The quantitative EEG as a screening
instrument to identify sedative effects of single doses of plant extracts in comparison
with diazepam. Phytomedicine 1998;5:449-458.
68. Herberg, K. W. Nebenwirkungen pflanzlicher Beruhigungsmittel/Leistung und
Befinden nach Einnahme einer Baldrian-Hopfen-Kombination. Z. Allg. Med. 1996;
72:234- 240.
69. Santini, F., Vitti, P., Ceccarini, G., Mammoli, C., Rosellini, V., Pelosini, C.,
Marsili, A., Tonacchera, M., Agretti, P., Santoni, T., Chiovato, L., and Pinchera, A. In
vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J.
Endocrinol. Invest. 2003;26(10):950-955.
70. Gyllenhaal, C., Merritt, S. L., Peterson, S. D., Block, K. I., and Gochenour, T.
Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Sleep Med.
Rev. 2000;4(3):229-251.
71. Agata, I., Kusakabe, H., Hatano, T., Nishibe, S., and Okuda, T. Melitric acids A
and B, new trimeric caffeic acid derivatives from Melissa officinalis. Chem. Pharm.
Bull. 1993; 41(9): 1608-1611.
72. Tagashira, M. and Ohtake, Y. New antioxidative 1,3-benzodioxole from Me-
lissa officinalis. Planta. Med. 1988;64(6):555-558.
73. Englberger, W., Hadding, U., Etschenberg, E., Graf, E., Leyck, S., Winkelmann,
J., and Parnham, M. J. Rosmarinic acid: A new inhibitor of complement C3- convertase
with anti-inflammatory activity. Int. J. Immunopharmacol. 1988;10(6): 729-737.
74. Cohen, R. A., Kucera, L.S., and Herrmann, E. C. Antiviral activity of Melissa
officinalis (lemon balm) extract (29600). Proceedings of the Society for Experimental
Biology and Medicine 1964;117:431-434.
75. Felklova, M., Natherova, L., and Duskova, K. [Tannin compounds in leaves of
Melissa officinalis L., invaded by Septoria melissae Desm]. Cesk. Farm. 1969;18(9):
76. Mulkens, A. and Kapetanidis, I. [Flavonoids of the leaves of Melissa officinalis
L. (Lamiaceae)]. Pharm.Acta Helv. 1987;62(1):19-22.
Natural Standard Review 111
77. Thieme, H. and Kitze, C. [Occurrence of flavonoids in Melissa officinalis L].
Pharmazie 1973;28(1):69-70.
78. Mikus, J., Harkenthal, M., Steverding, D., and Reichling, J. In vitro effect of es-
sential oils and isolated mono- and sesquiterpenes on Leishmania major and Trypanosoma
brucei. Planta Med 2000;66(4):366-368.
79. Brieskorn, C. H. and Krause, W. [Further triterpenes from Melissa officinalis L.
(author’s transl)]. Arch Pharm.(Weinheim) 1974;307(8):603-612.
80. Tittel, G., Wagner, H., and Bos, R. [Chemical composition of the essential oil
from Melissa]. Planta Medica 1982;46:91-98.
81. Hefendehl, F. W. [Composition of etheric oil of Melissa officinalis L. and sec-
ondary changes of oil composition]. Arch Pharm. Ber. Dtsch. Pharm. Ges. 1970;303(4):
82. Mulkens, A. and Kapetanidis, I. Eugenylglucoside, a new natural Phenyl-
propanoid Heteroside from Melissa officinalis. J. Nat. Prod. 1988;51:496-498.
83. Mulkens, A., Stephanou, E., and Kapetanidis, I. Heterosides a genines volatiles
dans les feuilles de Melissa officinalis L. (Lamiaceae). Pharma Acta Helv 1985;60:
84. Sarer, E. and Kökdil, G. Constituents of the essential oil from Melissa
officinalis. Planta Med 1991;57:89-90.
85. Mulkens, A. and Kapetanidis, I. Etude de l’huile essentielle de Melissa officinalis
L. (Laminaceae). Pharm Acta Helv. 1988;63:266-270.
86. Carnat, A. P., Carnat, A., Fraisse, D., and Lamaison, J. L. The aromatic and
polyphenolic composition of lemon balm (Melissa officinalis L., subsp officinalis) tea.
1998; 72:301-305.
87. Koch-Heitzmann, I. and Czygan, F. C. Über wasserdampfflüchtige Diterpen-
kohlenwasserstoffe in nicht differenzierten Oberflächenkulturen/Untersuchungen an
Kalluskulturen von Melissa officinalis L. 1985;II(40c):13-20.
88. Allahverdiyev, A., Duran, N., Ozguven, M., and Koltas, S. Antiviral activity of
the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2. Phyto-
medicine. 2004;11(7-8):657-661.
89. Larrondo, J. V., Agut, M., and Calvo-Torras, M. A. Antimicrobial activity of es-
sences from labiates. Microbios 1995;82(332):171-172.
90. Iauk, L., Lo Bue, A. M., Milazzo, I., Rapisarda, A., and Blandino, G. Antibacte-
rial activity of medicinal plant extracts against periodontopathic bacteria. Phytother.
Res. 2003;17(6):599-604.
91. Friedman, M., Henika, P. R., Levin, C. E., and Mandrell, R. E. Antibacterial ac-
tivities of plant essential oils and their components against Escherichia coli O157:H7
and Salmonella enterica in apple juice. J. Agric. Food Chem. 9-22-2004;52(19):
92. Mimica-Dukic, N., Bozin, B., Sokovic, M., and Simin, N. Antimicrobial and an-
tioxidant activities of Melissa officinalis L. (Lamiaceae) essential oil. J. Agric. Food
Chem. 5-5-2004;52(9):2485-2489.
93. Peake, P. W., Pussell, B. A., Martyn, P., Timmermans, V., and Charlesworth, J.
A. The inhibitory effect of rosmarinic acid on complement involves the C5 convertase.
Int. J. Immunopharmacol. 1991;13(7):853-857.
94. Dimpfel, W., Pischel, I., and Lehnfeld, R. Effects of lozenge containing laven-
der oil, extracts from hops, lemon balm and oat on electrical brain activity of volun-
teers. Eur. J. Med. Res. 9-29-2004;9(9):423-431.
95. Ivanova, D., Gerova, D., Chervenkov, T., and Yankova, T. Polyphenols and an-
tioxidant capacity of Bulgarian medicinal plants. J. Ethnopharmacol. 1-4-2005;96(1-2):
96. Marongiu, B., Porcedda, S., Piras, A., Rosa, A., Deiana, M., and Dessi, M. A.
Antioxidant activity of supercritical extract of Melissa officinalis subsp. officinalis and
Melissa officinalis subsp. inodora. Phytother. Res. 2004;18(10):789-792.
97. de Sousa, A. C., Alviano, D. S., Blank, A. F., Alves, P. B., Alviano, C. S., and
Gattass, C. R. Melissa officinalis L. essential oil: Antitumoral and antioxidant activi-
ties. J. Pharm. Pharmacol. 2004;56(5):677-681.
98. Drozd, J. and Anuszewska, E. The effect of the Melissa officinalis extract on im-
mune response in mice. Acta Pol. Pharm. 2003;60(6):467-470.
99. McCue, P. P. and Shetty, K. Inhibitory effects of rosmarinic acid extracts on
porcine pancreatic amylase in vitro. Asia Pac. J. Clin. Nutr. 2004;13(1):101-106.
100. Soulimani, R., Younos, C., Fleurentin, J., Mortiert, F., Misslin, R., and Derrieux,
G. Recherche de l’Activit, biologique de Melissa officinalis L. sur le Systéme nerveux
central de la souris in vivo et le Doudenum de Rat in vitro. Plant Med Phytother
101. Salah, S. M. and Jager, A. K. Screening of traditionally used Lebanese herbs for
neurological activities. J. Ethnopharmacol. 2-10-2005;97(1):145-149.
102. Gazola, R., Machado, D., Ruggiero, C., Singi, G., and Macedo, Alexandre M.
Lippia alba, Melissa officinalis and Cymbopogon citratus: Effects of the aqueous ex-
tracts on the isolated hearts of rats. Pharmacol. Res. 2004;50(5):477-480.
103. Vogt, M., Tausch, I., Wölbling, R. H., and Kaiser P. M. [Melissa extract in her-
pes simplex: A double-blind placebo-controlled study]. Der Allgemeinarzt 1991;
104. Lagoni, N. Wirksamkeitsprüfung eines pflanzlichen Tagessedativums in einer
multizentrischen Studie. 1998;39(3):166-169.
105. Schmidt, U., Krieger, W., Frerick, H., and Schenk, N. Psychosomatische und
psychische Störungen/Baldrian und Melisse statt synthetischer Psychopharmaka. 1992;
106. Chakurski, I., Matev, M., Koichev, A., Angelova, I., and Stefanov, G. [Treat-
ment of chronic colitis with an herbal combination of Taraxacum officinale,Hipericum
perforatum,Melissa officinalis,Calendula officinalis and Foeniculum vulgare]. Vutr.Boles.
107. Madisch, A., Holtmann, G., Mayr, G., Vinson, B., and Hotz, J. Treatment of
functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-
controlled, multicenter trial. Digestion 2004;69(1):45-52.
108. Borho, B. Biologische Therapie von funktionellen Magenerkrankungen. 1991;6:
109. Dressing, H., Kohler, S., and Muller, W. E. Improvement in sleep quality with a
high dose valerian-melissa preparation. Psychopharmakotherapie 1996;3:123-130.
110. Lindahl, O. and Lindwall, L. Double blind study of a valerian preparation.
Pharmacol. Biochem. Behav. 1989;32(4):1065-1066.
Natural Standard Review 113
111. Widy-Tyszkiewicz, E., and Schminda, R. A randomized double blind study of
sedative effects of phytotherapeutic containing valerian, hops, balm and motherwort
versus placebo. Herb Polon. 1997;2:154-159.
112. Orth-Wagner, S., Ressin, W. J., and Friedrich, I. Phytosedativum gegen
Schlafstörungen/Klinische Wirksamkeit und Verträglichkeit eines Phytosedativums
mit Auszügen aus Baldrianwurzel, Hopfenzapfen und Melissenblättern. 1995; 16(147):
... officinalis L. (Lamiaceae) (MO)) is a widely used medicinal plant, for the treatment of depression, anxiety, insomnia, anxiety-induced palpitation, and stress. It is used in central and southern Europe, the Mediterranean region, and west Asia as a folks herbal medicine (Ghazizadeh et al., 2021;Shakeri et al., 2016;Ulbricht et al., 2005). It is worth mentioning that MO essential oil (MOEO) is traditionally used by Austrian folk to treat various ailments, including those related to central nervous system (Vogl et al., 2013). ...
... Even though the primary bioactive compounds remain to be elucidated (Ghazizadeh et al., 2021), the neurological effects of this plant are previously connected mainly with the presence of rosmarinic acid. Also, some other water-soluble constituents such as caffeic acids, chlorogenic acid, and metrilic acid in MO aerial parts extract (Ghazizadeh et al., 2020;Ulbricht et al., 2005). Surprisingly, according to a SciFinder search of the Chemical Abstracts Service (CAS) database, at the time of the investigation, there were only a few reports with attention to the anxiolytic effects of the volatile constituents that are part of the MOEO (Huang et al., 2008). ...
... MO has been used for centuries to treat different central nervous system disorders (Ulbricht et al., 2005;Vogl et al., 2013). Various formulations for this plant are utilized (Ulbricht et al., 2005), from which the essential oil, a specific and valuable source of active compounds, has been unreasonably neglected since there are only few reports dealing with its activity (Abdellatif et al., 2021;Chindo et al., 2021;Sousa et al., 2004), even though its application is widely spread (Ulbricht et al., 2005;Stojanović et al. 2017Stojanović et al. , 2022. ...
Ethnopharmacological relevance: Among the fewest drugs discovered are those belonging to the class of anxiolytics. Although some drug targets for anxiety disorders are established, it is hard to modify and selectively choose the active principle for those targets. Thus, the ethnomedical approach to treating anxiety disorders remains one of the most prevalent ways for (self)managing the symptoms. Melissa officinalis L. (lemon balm) has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, especially dose related to restlessness. Aim of the study: This work aimed to evaluate the anxiolytic activity, in several in vivo models, of the essential oil extracted from Melissa officinalis (MO) and its main constituent citronellal, a widespread plant utilized for managing anxiety. Materials and methods: In the present study several animal models were used to assess MO anxiolytic potential in mice. The effect of the MO essential oil applied in doses ranging from 12.5 to 100 mg/kg was estimated in light/dark, hole board, and marble burying tests. In parallel doses of citronellal corresponding to the ones in the MO essential oil were applied to animals to determine if this is the activity carrier. Results: The results indicate that the MO essential oil exerts anxiolytic potential in all three experimental settings by significantly altering the traced parameters. The effects of citronellal are somewhat inconclusive and should not be interpreted only as anxiolytic but rather as a combination of anti-anxiety and motor-inhibiting effects. Conclusions: In conclusion, we could say that the results of the present study provide a base for future mechanistic studies that would evaluate the activity of M. officinalis essential oil on various neurotransmitter systems involved in the generation, propagation, and maintenance of anxiety.
... Investigações fitoquímicas levaram ao isolamento de flavonóides, terpenóides, cumarinas e óleos essenciais. Os flavonoides quercetina, luteolina e apigenina foram os principais constituintes descritos para a espécie, exibindo atividades ansiolítica e antidepressiva [17,18] [17] Hipoglicemiantes De efeito Hipoglicemia [17,18] AINEs De efeito Hemorragias e alterações na coagulação sanguínea [17] M. officinalis ISRS e BZD De efeito Potencialização dos efeitos sedativos [10] B. trimera ...
... Anti-hipertensivos De efeito Hipotensão [10,26] Antiagregante plaquetários De efeito Exacerbação dos efeitos antiagregante plaquetários [10,26] BCC, BZD e estatinas Farmacocinética Alteração da metabolização [9,10,25,32] P. anisum antidepressivos De efeito Exacerbação dos efeitos [33] AINEs Farmacocinética Redução da biodisponibilidade [34] Estudos sugerem que a espécie é efetiva no tratamento de hiperglicemia e complicações diabéticas, [10,11] . Na sua composição destacam-se óleos essenciais (geranial, ceral, citronelal), triterpenos (ácido ursólico e ácido oleanólico), flavonoides e compostos fenólicos (ácido cafeico, luteolina, narigenina, apigenina) e o ácido rosmarínico [10,11] . ...
... Anti-hipertensivos De efeito Hipotensão [10,26] Antiagregante plaquetários De efeito Exacerbação dos efeitos antiagregante plaquetários [10,26] BCC, BZD e estatinas Farmacocinética Alteração da metabolização [9,10,25,32] P. anisum antidepressivos De efeito Exacerbação dos efeitos [33] AINEs Farmacocinética Redução da biodisponibilidade [34] Estudos sugerem que a espécie é efetiva no tratamento de hiperglicemia e complicações diabéticas, [10,11] . Na sua composição destacam-se óleos essenciais (geranial, ceral, citronelal), triterpenos (ácido ursólico e ácido oleanólico), flavonoides e compostos fenólicos (ácido cafeico, luteolina, narigenina, apigenina) e o ácido rosmarínico [10,11] . ...
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A prevalência de doenças crônicas como Hipertensão Arterial Sistêmica (HAS) e Diabetes Mellitus (DM) fomenta a procura por tratamentos alternativos em adição à farmacoterapia convencional, com destaque para as plantas medicinais. Porém, a falta de informações sobre as plantas medicinais, suas interações com medicamentos e a automedicação são fatores preocupantes. Os objetivos do estudo foram identificar as plantas medicinais e as classes farmacológicas utilizadas por portadores de HAS e/ou DM cadastrados no programa Hiperdia em Governador Valadares, MG, caracterizar esses usuários e pesquisar possíveis interações entre as plantas medicinais e a farmacoterapia. Realizou-se um estudo transversal com questionário semiestruturado. Dos entrevistados 66,2% são portadores de HAS, 9% de DM e 24,8% de ambas as patologias. A maioria (52,4%) faz uso de plantas medicinais e 46,2% estão sujeitos a algum tipo de interação planta-medicamento, como o uso de Baccharis trimera, Allium sativum, Rosmarinus officinalis e Plectranthus barbatus e anti-hipertensivos ou Allium sativum e Matricaria chamomilla com antidiabéticos orais. Nesse sentido, a avaliação das interações planta-medicamentos, adequação da terapia e orientação dos pacientes são ferramentas fundamentais na prevenção de efeitos indesejáveis, contribuindo para o uso racional das plantas medicinais e melhoria na qualidade de vida dos portadores de HAS e DM.
... [15,16] Lemonbalm (Melissa officinalis L., Lamiaceae) can be effective in treating dementia and forgetfulness, as well as improving behavioral symptoms in anxiety disorders, cognitive disorders, insomnia, and stress. [17][18][19][20] Cinnamon (Cinnamomum verum J. Presl, Lauraceae) possesses neuroprotective activity against Parkinson's and AD, is traditionally used in age-related brain disorders, and plays a role in multidisciplinary mechanisms. [21][22][23] Long pepper (Piper longum, Piperaceae) has anti-Parkinson's therapeutic activities and is used in Ayurveda and Iranian traditional medicine to delay and control dementia. ...
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Objective: This study aimed to assess the efficacy of an herbal formulation based on Boswellia sacra in improving cognitive and behavioral symptoms in patients with mild cognitive impairment (MCI) and mild-to-moderate stages of Alzheimer's disease (AD). Methods: A 3-month, parallel-group, placebo-controlled trial was implemented from October 2021 to April 2022. Patients with MCI and mild-to-moderate stages of AD aged above 50 years (n = 60; 40 women, 20 men) enrolled in the study using clinical diagnosis and a score of 10-30 on the mini-mental state examination (MMSE) test. They were assigned into two groups; one receiving a herbal formulation) include B. sacra, Melissa officinalis, Piper longum, Cinnamomum verum, and Physalis alkekengi) three times a day and the other receiving a placebo for 3 months. The main efficacy measures were the changes in cognitive domains based on the MMSE and changes in behavioral and psychiatric symptoms based on neuropsychiatric inventory (NPI) scores compared with baseline. Side effects were also recorded. Findings: Results of this study showed significant differences between the two groups after 3 months in terms of all the assessed variables, including the overall result of the mean score of MMSE and NPI tests (P ≤ 0.001). The herbal formulation had the most considerable effects on the domains of orientation, attention, working memory, delay recall, and language of the MMSE test. Conclusion: Herbal formulation based on B. sacra was significantly effective compared to a placebo in improving cognitive and behavioral symptoms in patients with MCI and mild-to-moderate AD.
... Melissa officinalis L. is an aromatic herb native to southern Europe, W. Asia, and The Mediterranean Sea region, this plant is now widely cultivated. Lemon balm has been used in medicinal folkloric remedies 3 . It has been used to treat a variety of health diseases, including the neurological, antimicrobial, central nervous system, anti-malignant, cardiovascular, respiratory, and antidepressant problems, as well as to improve memory in dementia patients. ...
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Abstract: Phytochemical investigation of 70% aqueous methanol extract of leaves of lemon balm (Melissa officinalisL., Lamiaceae) was subjected to different chromatographic separation techniques. The structures of isolated compounds were determined based on spectral data (UV, 1H-NMR, 13CNMR, and mass spectrometry). Also, assessment of the antioxidant, anticonvulsant, anti-inflammatory as well as antimicrobial activities was determined using different techniques. Result: three isoflavones;4'- methoxy genistein Biochanin A] (1),6, 8 dimethoxy- biochanin A -7 - O- α - L- rhamnopyranosyl (1'''-6'') - O -  - D- glucopyranoside (2), isoflavone 6, 8dimethoxy 7-O- - D rutinoside, 4'-O- α- L-rhamnopyranoside (3).Besides six known flavonoids; hyperin (4), luteolin 7-O- rhamnoside(5), scutellarein – 4',7 dimethyl ether(6), nepetin - 7- methyl ether(7),luteolin(8),and apigenin (9),in addition to caffeic acid(10), chlorogenic acid (11) isolated for the first time from Melissa officinalis. The examined extract revealed significant anticonvulsant activity, effective in inhibition of both acute & chronic inflammation. Scutellarein – 4',7-dimethyl ether (6) showed remarkable inhibition against fungi and exhibited the highest antibacterial effect against both Gram +ve and Gram -ve bacteria. The above evidence suggests that Melissa officinalis leaves are a good supply of natural isoflavones that can be utilized to avoid convulsion, and inflammation, as well as an antioxidant and antimicrobial supplement.
... On the other hand, a randomized controlled trial using a single dose of M. officinalis extract comprising 500 mg rosmarinic acid, showed to be harmless and well tolerable in healthy humans [112]. This is confirmed by randomized clinical trials where different treatment regimens of M. officinalis extracts also showed no adverse effects in humans [84,94,95,113]. Overall, though M. officinalis toxicity data are scarce and have been poorly investigated despite the variety of practical applications in medical science, available data point out its putative safety in human beings. ...