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Melissa officinalis

Melissa officinalis (Lemon Balm) is a herb/tea traditionally said to induce calmness and improve cognition. It does appear effective at inducing calmness and reducing anxiety, but the cognitive enhancing properties are variable (appears to benefit if stressed, but otherwise it is merely sedative).

Our evidence-based analysis on melissa officinalis features 41 unique references to scientific papers.

Summary of Melissa officinalis

Primary Information, Benefits, Effects, and Important Facts

Melissa officinalis (Lemon Balm) is a herb that has traditionally been used for a variety of cognitive purposes, most of which are centered around improving cognition and reducing stress and anxiety. It is said to calm the nerves and to relax the body.

In regards to its subjective cognitive effects, it appears to be effective in inducing calmness. This may also manifest itself in a negative manner as healthy persons who take Lemon Balm prior to a cognitive test appear to score worse than placebo on reaction time and memory formation (possibly related to sedation) while improving the quality of memories (amount of correct memories formed, rather than 'remembering' something that didn't happen). Only one study looked at contentment, but found no influence.

Theoretically, calmness inducing agents should also help in sleep. We currently have one study suggesting that the anxiety-reducing properties can help people who have anxiety-related insomnia but beyond that most sleep research is confounded with Valerian as the two are theoretically (not yet demonstrated) additive or synergistic.

Overall, the cognitive enhancing properties of Lemon Balm appear to be somewhat overhyped. It has been shown to enhance the memory quality yet (possibly due to its sedative effects) it reduces quantititatively how many memories are formed and the rate thereof.

Currently, Lemon Balm appears to be supported for inducing calmness and relaxation but other claims may need more research.


Things To Know & Note

Is a Form Of

Primary Function:

Also Known As

Lemon Balm, Melissengeist, Bee balm, Garden Balm, Melissa, Erva-cidreira

Do Not Confuse With

Limonene (sometimes called Lemon extract)

Caution Notice

Examine.com Medical Disclaimer

  • Although ethanolic extracts have more of the bioactives, a tea of Lemon Balm may also confer some bioactive properties

How to Take Melissa officinalis

Recommended dosage, active amounts, other details

The lowest active supplemental dose appears to be 300mg, and supplementation above this dose appears to confer dose-dependent effects although it is not very reliable (ie. one study says that 1200mg gives thrice as much benefit as 300mg while another suggests 1.4x benefit)

Lemon Balm bioactives may also be consumed via tea or acquired via aromatherapy, although it is much harder to quantify 'the right dose' via these two methods.

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects melissa officinalis has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Memory Minor High See all 3 studies
Mixed influences on memory, with one study noting a decrease in 'total' memory formation and two studies noting improvements in 'quality' of memories formed. There is likely a modulatory effect associated with lemon balm.
grade-c Alertness Notable Very High See 2 studies
A decrease in alertness appears to occur alongside lemon balm ingestion (with or without sedation)
grade-c Calmness Notable Very High See 2 studies
An increase in self-reported ratings of 'calmness' appears to exist following ingestion of lemon balm single doses
grade-c Anxiety Minor Very High See 2 studies
A decrease in anxiety has been noted with lemon balm extract, although not to a remarkable degree
grade-c Processing Speed Minor - See study
A decrease in processing speed appears to occur following lemon balm ingestion, which may be related to the sedation effects
grade-c Stress Minor - See study
A decrease in self-reported stress has been reported with lemon balm
grade-c Attention - - See study
Despite the decrease in alertness seen with lemon balm, there does not appear to be any alterations in intentional attention
grade-c Contentment - - See study
No significant influence on self-ratings of contentment despite the increase in calmness
grade-c Working Memory - Very High See 2 studies
No significant influence appears to exist on working memory associated with lemon balm
grade-d Aggression Minor - See study
A reduction in agitation has been noted with lemon balm in stressed and anxious subjects, perhaps secondary to alleviating anxiety
grade-d DNA Damage Minor - See study
A reduction in DNA damage has been noted with lemon balm tea in persons exposed to high levels of radiation
grade-d Fatigue Minor - See study
A decrease in fatigue associated with anxiety has been noted, no research looking at the per se influence of lemon balm on fatigue
grade-d General Oxidation Minor - See study
A decrease in general oxidation occurs following lemon balm ingestion
grade-d Insomnia Minor - See study
A decrease in insomnia has been noted to be to quite a large degree in one open-label trial, but may be secondary to anxiety reduction
grade-d Lipid Peroxidation Minor - See study
A slight decrease in biomarkers of lipid peroxidation occurs following ingestion of lemon balm
grade-d Relaxation Minor - See study
An increase in self-reports of relaxation occur, which may be related to the increased calmness and sedation ratings also seen

Studies Excluded from Consideration

Scientific Research on Melissa officinalis

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1Sources and Compostion

1.1Sources

Melissa officinalis (from the Labiatae family) is a herb commonly called Lemon Balm with some traditional uses in nervous system ailments, memory enhancement, and sedation.[3][4] It appears to have traditional usage in Eastern Europe, particularly Croatia,[5] and has a documented medicinal history extending back to the 'Materia Medica' in approximately 50–80 BC[6] and beyond 'Lemon Balm' is also sometimes referred to as either Bee Balm or Garden Balm, sometimes simply as 'Melissa'.[7]

Melissa officinalis also appears to have a medicinal presence in Brazil where it is referred to as 'erva-cidreira'.[8]

A herb that appears to have European traditional usage for the purposes of sedation, cognitive boosting, and calming the body. The traditional uses vary from oral herb intake, tea drinking, and aromatherapy

1.2Composition

Lemon Balm contains:

  • Caffeate Oligomers up to 11%,[9] this includes the following Rosmarinic Acid, Caffeic acid methyl esters, and melitric acids (A and B)[9] 

  • Rosmarinic Acid at 22.96-55.68mg/g on the low end[10] yet 232-255mg/g (60% ethanolic extract);[5] due to these, tinctures of Lemon Balm with an alcohol extraction appear to be better sources of Rosmarinic acid, and dried leaves appear to also confer greater Rosmarinic acid content[11]

  • Rosmarinic Acid hexoside and sulfated versions are present at 1.98-3.49mg/g and 2.45-6.34mg/g, respectively[10]) as well as Methyl esters[12]

  • Caftaric acid (as hexoside at 0.44-0.63mg/g[10]), caffeic acid (32.39mg/g[5]), and p-coumaric acid[13]

  • Melitric Acid A and B[14]

  • 1,3-Benzodioxole[12]

  • Yunnaneic acid F (0.01-0.35mg/g[10])

  • Salvianolic acid A (1.29-4.08mg/g[10]), B (1.12-1.77mg/g[10]), derivatives of C (three molecules ranging from 1.25-8.50mg/g at peak values[10]), and an isomer of F (0.23-0.77mg/g; sometimes undetectable[10])

  • Lithospermic acid A (6.84-17.97mg/g[10]) and isomer (7.09-11.64mg/g[10])

  • Sagerinic acid (0.36-2.17mg/g[10])

  • Protocatechuic Acid[12][15]

  • Triterpenoids Carnosic Acid, Ursolic Acid, and Oleanolic Acid

  • Kaempferol diglucoside[13] although sometimes undetectable[5]

  • Quercetin glucoside[13]

  • Apigenin (as 7-O-beta-D-glucopyranoside)[16]

  • Luteolin-3′-O-glucuronide[17][18] (1.22-8.43mg/g[10]) with another study noting Luteolin aglycone was at 0.81-1.21mg/g[5]

  • Galactolipids (lipids bound to galactose), including 25 monogalactosyldiacylglycerols and 13 digalactosyldiacylglycerols[19]

While the essential oil fragment contains:

  • Monoterpene hydrocarbons known as Sabinene, β-Pinene (0.32%), Limonene, and Phellandrene[20]

  • Oxygenated monoterpenes known as Geranial (65.42%), Neral (24.65%), Geranylacetate (7.38%), Linalool (0.75%), (Z)-Carveol and Myrtenol (0.08%), 2,3-dehydro-1,8-cineole (0.05%), Carvacrol, Epoxylinalool, α-Terpeniol, Borneol, Neroloxide, Citronellal and Citronellyl acetate, Terpinene-4-ol, Anethole, Menthen-2,3-diol, Damascenone, Dihydrocarveol, and Eugenol[20]

  • Sesquiterpene hydrocarbons known as Bicyclogermacrene, Caryophyllene (0.77%), Germacrene-D, Farnesene (0.05%), γ-Elemene, and Cadinene[20]

  • Carbonyl compound known as Nonanal, (Z)-Jasmone, and β-Ionone[20]

  • The alcohols Benzylalcohol, Fenchylalcohol, and Chavicol[20]

  • 1-Dodecen-3-yne (0.09%), Dodecane, Isogeranol, and Bourbonene[20]

For common plant compounds that have failed to be detected in Lemon Balm, there does not appear to be a Chlorogenic acid content nor a ferulic acid content.[5]

For the most part, Lemon Balm appears to be high in Caffeic acid and caffeic acid-like molecules including Rosmarinic Acid while being comparatively low in triterpenoids and other polyphenolics; although the 'major' flavonoid is Luteolin (as Glucuronide) it is still in very low concentrations and likely not bioactive

The total phenolic content appears to be highest in water extracts relative to methanolic and ethanolic,[21] with plant extracts reaching 54.9+/-2.14mg (5.5%; Gallic acid equivalents) and tea extracts containing up to 109.24mg/g (10.9%) phenolics by weight.[10] The phenolic content of Lemon Balm appears to be greater than that of Lavandula angustifolia (Lavender) while lesser than that of Origanum vulgare (Oregano)[13] and Menthae piperitae (Peppermint).[9] It is comparable to blackberry leaves and Thyme, but greater than that of Olive leaves and Stinging Nettle.[5]

The flavonoid content of Lemon Balm is approximately 47% of the total phenolics, and appears to have more Kaempferol relative to Quercetin (3.5:1 ratio approximately)[13] although this may not be reliable as other studies note a different ratio or no detectable Kaempferol.[5] There appears to be a tannin content as well, reaching 5.18+/-0.73mg/g after 15 minutes of extraction and 8.62+/-0.96mg/g when hydrolyzed.[5]

The essential oil (aromatic) component of Lemon Balm is merely 0.32% of the herb in regards to total dry weight, with a tea extracting 10mg/L.[22]

Quantitatively speaking, Lemon Balm appears to be a very large source of phenolic compounds (in general; anything with a benzene ring is a phenolic with multiple ring structure being 'polyphenolic' in structure)

2Neurology

2.1GABAergic mechanisms

In regards to GABA (primary sedative neurotransmitter), the methanolic extract appears to have GABAergic activity secondary to inhibiting the enzyme GABA transaminase (IC50 of 0.55+/-0.2mg/mL) to a greater degree than hexane (none detected), ethyl acetate (2.55+/-0.28mg/mL), and water extracts (0.82+/-0.03mg/mL).[23] The molecules that appear to be most active in this regard are ursolic acid (5.0+/-3.6% inhibition at 1µg/mL and 19.9+/-10.6% inhibition at 100µg/mL), oleanolic acid (20.2+/-11.1% at 10µg/mL), and rosmarinic acid (4.6+/-2.2% inhibition at 1µg/mL and 40.4+/-3.2% at 100µg/mL) while ursolic acid appeared to be slightly synergistic when paired with oleanolic acid.[23]

A reduced concentration of GABA transaminase has been noted in vivo following 50-200mg/kg oral ingestion in aged rats over 5 weeks, when the hippocampal dentate gyrus was removed and assessed.[24]

Appears to have GABAergic activity, although by a mechanism not common to other nutraceuticals (possible additive or synergistic possibilities that are not yet explored)

2.2Sleep

In a 15 day open-label study in persons with mild to moderate stress and anxiety coupled with sleep disturbances, supplementation of Melissa officinalis (7% Rosmarinic acid and 15% total hydrocinnamic acids) taking 300mg at breakfast and again before sleep (600mg total) noted reductions in anxiety-related insomnia by 42% (Overall).[25]

Melissa officinalis is commonly consumed alongside Valerian for the purpose of sedation, and at least one multicenter study using both in a combination noted that the supplement group (120mg Valerian (4.5:1 concentration) and Lemon Balm at 80mg (5:1 concentration) taken thrice before bed) after 30 days reported enhanced sleep quality (33% of respondents reported better sleep) which was greater than placebo (9% of the placebo group reported better sleep); treatment was very well tolerated with no significant side effects.[1] One other trial has noted that this combination was effective in reducing restlessness and dyssomnia in children.[2]

Appears to have sedative properties and promote sleep quality, but there is relatively little evidence to support it as two well controlled studies are confounded with the inclusion of Valerian

2.3Anxiety and Stress

In rats given Melissa officinalis extract (9.32% Rosmarinic Acid) at 120-360mg/kg bodyweight for 15 days appeared to have anxiolytic effects in an open field test as well as an elevated maze test but not in a four-hole board test at the higher two doses (240mg/kg and 360mg/kg).[26] The anxiolyic effects (30-300mg/kg ethanolic extract) have in one study been comparable to 1mg/kg Diazepam when dosed over 10 days, and appeared to be more effective in females (with only 300mg/kg being statistically significant in males, but all doses being effective in female rats).[27]

One study has noted that inhalation of lemon oil vapor has exerted anti-stress responses, and that these effects were related to serotonergic signalling (particularly the receptor 5-HT1A).[28]

Two animal studies suggest anxiety reducing effects of oral Lemon Balm, with one noting that lemon vapor was also effective

In a clinical setting, an acute dose of 300 or 600mg Melissa officinalis prior to an acute stress test (DISS battery of tests[29] followed with Mood assessment via Bond and Lader VAS mood scales[30]) noted that the higher dose was associated with improved self-reported calmness, reduced alertness (increased after test) following the test while the 300mg dose failed to significantly modulate mood.[31] Another acute study noted that a Lozenge containing Melissa officinalis was able to induce brain wave alterations similar to that of standard anxiolytics.[32]

Can reduce anxiety when dosed acutely (single dose taken before stressor)

In humans consuming 300mg Melissa officinalis (7% Rosmarinic acid and 15% total hydrocinnamic acids) at breakfast and again before sleep for 15 days in an open-label trial, there appears to be general anxiolytic propeties in regards to anxiety-related eating problems (33% lower than baseline), emotional instability (7%), fatigue (18%), feelings of guilt (15%) or inferiority (18%), psychosomatic symptoms (33%) and intellectual disturbance (28%).[25]

Appears to reduce anxiety when taken over a period of time in humans (morning and nightly doses)

2.4Memory and Learning

One study has noted that Melissa officinalis have nicotinic receptor binding properties[33] as well as muscarinic.[34] One study has noted weak acetylcholinesterase inhibiting property with fresh, but not dried, leaves of Lemon Balm;[33] a subsequent study failed to replicated acetylcholinesterase inhibiting properties up to 0.25mg/mL.[6]

Subsequently, a study conducted noting incubation with Melissa officinalis noted that the extract had little ability to displace either nicotine or scopolamine from the receptor.[35] This was followed up on in post-mortem human neural tissue where nicotine was displaced at moderate concentrations of 180-3120µg/mL and scopolamine at 2.69-4.31mg/mL (ethanolic herb extract) although it could be extracted into more effective fractions (the most potent noted fractions being 4.2µg/mL nicotine displacement and 102.6µg/mL for scopolamine) although there still appears to be a large degree of variability.[6] 

Appears to interact with acetylcholine receptors, there appears to be some agonistic (activating) properties that are very volatile (not reliable); if looking at solely the most effective fragments, the affinity at least appears respectable

In the hippocampal dentate gyrus of aged rats, Melissa officinalis at 50-200mg/kg daily was able to enhance neurogenesis (244.1-763.9% of control group, respectively) which was associated with reduced corticosterone concentrations.[24]

Has been noted to enhance neurogenesis in at least one rat study giving oral administration

300mg Melissa officinalis given prior to an acute stress test was noted to be (nonsignificantly) associated with improved answering on mathematical questions; increasing the dose to 600mg did not help in reaching statistical significance.[31]

Following ingestion of 600mg or 1600mg Melissa officinalis acutely, improvements relative to placebo are noted in quality of memory (percentage of answers or recollections that are correct) only with trends for improvement (not significant) were noted in picture-recall, delayed word recall, spatial memory and no influence was noted on working memory nor attention in this study, and self-reported attention was similar.[6] Sporadic improvements in memory quality (digital vigilance accuracy and choice reaction time accuracy) have been noted elsewhere.[35]

There appears to be comparatively weak cognitive enhancing properties assocaited with oral Melissa officinalis supplementation at higher doses (600-1600mg)

For cognitive parameters sometimes seen as adverse, 600-1600mg Melissa officinalis has been noted to reduce the speed of memory without influencing memory formation per se.[6] A reduction in rapid visual information processing has also been noted, with sporadic influences on false-positive processing (neither 600 nor 1600mg, but 1000mg, being associated with increased false-positives).[6] Another study to record spatial memory found a statistically significant reduction thereof following 300-900mg acute ingestion, this reduction was also noted for word recollection.[35]

The calming effects of Melissa officinalis may also reduce the speed of learning, possibly secondary to being slightly sedative or too 'calming'

2.5Neuroprotection

In hippocampal corticol neurons deprived of oxygen, 10μg/mL Lemon Balm was associated with preserving roughly half of corticol neurons that would have been lost to hypoxia and also reduced concentrations of caspase-3 and DNA fragmentation (both indicative of apoptosis); concentrations of 200-500μg/mL showed inherent cytotoxicity to neurons.[4] Neuroprotection has also been noted in hippocampal cells exposed to ecstasy.[36]

Appears to have neuroprotective effects in vitro in pro-oxidative toxicity

In a model of hippocampal occlusion (mice) given 100mg/kg Lemon Balm for 2 weeks prior to occlusion treatment and continued thereafter noted reduced lipid peroxidation (MDA and TEAC) and the concentrations of HIF-1α, TNF-α and IL1-β (all induced during hypoxia) were effectively suppressed by Melissa officinalis.[4]

This may extend to living models undergoing hypoxia (lack of oxygen) in neural tissue

2.6Pain

One study has note dose-dependent pain-reducing effects of oral ingestion of Melissa officinalis (ID50 of 241.9mg/kg) in mice subject to a battery of tests (acetic acid writhing, glutamate, and formalin) which seems to be related to the Rosmarinic acid content.[37]

May have pain relieving properties, requires more research

3Interactions with Glucose Metabolism

3.1Interventions

One study using solely the essential oil of Lemon Balm at 0.0125mg daily in mice (0.416mg/kg; human equivalent of 0.03mg/kg) for 6 weeks noted that, in response to an oral glucose tolerance test, the essential oil group experienced a reduction in serum glucose and increase in serum insulin.[20]

One study suggests improved glucose tolerance following oral administration over a period of weeks, no clue as to the mechanisms underlying these observed effects (some alterations in adipocyte GLUT4 and PPARy of questionable relevance)

4Inflammation and Immunology

4.1Virology

A hydroalcoholic extract of lemon balm leaves were noted to reduce the cytopathic effects of HSV-2 (Vero cells) in the range of 0.025–1mg/mL with a maximal inhibitory level of 60% achieved at 0.5mg/mL.[38] Relative to the active control of Acyclovir (0.5µg/mL causing 94+/-3% inhibition), Lemon Balm severely underperformed.[38]

5Interactions with Oxidation

5.1Mechanisms

Anti-oxiditive properties appear to exist in the water, ethanolic, and methanolic extracts of Lemon Balm with the water extract being most effective (study conducted on TBARS rating of lipid peroxidation in brain tissue);[21] the IC50 for reducing TBARS induced by iron was 15.67+/-2.03µg/mL and 11+/-0.6µg/mL for oxidation induced by Sodium nitroprusside while the IC50 values of extracts in a DPPH assay ranged from 24.3-32.9µg/mL.[21]

The anti-oxidative properties of Lemon Balm were greater than Matricaria recutita and Cymbopogon citratus, but less than isolated Quercetin or Gallic Acid.[21]

Appears to have anti-oxidative properties in vitro which are more potent than many other herbs, but overall not too remarkable as they are outperformed by other supplemental references

In rats, 250mg/kg has been shown to protect rats from genotoxicity induced by Methyl methanesulfonate when Melissa officinalis is preloaded for two weeks.[8] 500mg/kg was also effective, but the two doses did not have any significant differences between them.[8]

One study conducted in radiology staff chronically exposed to low levels of radiation noted that ingestion of 1.5g Lemon Balm tea in 100mL water for 30 days was confirmed to reduce DNA oxidative damage, Myeloperoxidase, and lipid peroxidation.[39] 

Anti-oxidative effects have been confirmed in humans given 1.5g of lemon balm tea leaves daily

6Interactions with Cancer Metabolism

6.1Colon

In HCT-116 colon cancer cells, both the water extract and 50% methanolic extract showed anti-proliferative effects with the ethanolic extract reducing cell viability to 40% at 5μg/mL (72 hours) while it was further reduced to 13% at 1,000μg/mL; these were reported to be similar to both the water extract and Triton control at similar concentrations.[40]

7Nutrient-Nutrient Interactions

7.1Valerian

Lemon Balm and Valerian are commonly used in conjunction with one another for the purpose of sleep, as Lemon Balm is able to inhibit the GABA transaminase enzyme weakly (which converts GABA into Glutamate) while Valerian bioactives also weakly stimulates Glutamate Decarboxylase (which converts Glutamate into GABA); this combination is thought to cause a two-pronged stimulation of GABA concentrations in the brain secondary to inhibiting breakdown and stimulating synthesis of GABA.[41]

The combination has been tested in a multicenter study where tolerability was excellent (no reported side effects) although the benefits also lacklustre (more self-reports of 'no effect' than 'benefit' in regards to sleep), although the amount of persons reporting better sleep (33%) was still greater than placebo (9%).[1]

Commonly used together and theoretically additive, no evidence to support synergism

References

  1. ^ a b c Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double-blind, placebo-controlled, multicentre study).
  2. ^ a b Müller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine. (2006)
  3. ^ Ghaffariyan S, Mohammadi SA, Aharizad S. DNA isolation protocol for the medicinal plant lemon balm (Melissa officinalis, Lamiaceae). Genet Mol Res. (2012)
  4. ^ a b c Bayat M, et al. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo. Daru. (2012)
  5. ^ a b c d e f g h i Komes D, et al. Phenolic composition and antioxidant properties of some traditionally used medicinal plants affected by the extraction time and hydrolysis. Phytochem Anal. (2011)
  6. ^ a b c d e f Kennedy DO, et al. 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. (2003)
  7. ^ Rasmussen P. Lemon balm--Melissa officinalis; also known as lemon balm, bee balm, garden balm, Melissa, melissengeist. J Prim Health Care. (2011)
  8. ^ a b c de Carvalho NC, et al. Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice. Genet Mol Biol. (2011)
  9. ^ a b c Fecka I, Turek S. Determination of water-soluble polyphenolic compounds in commercial herbal teas from Lamiaceae: peppermint, melissa, and sage. J Agric Food Chem. (2007)
  10. ^ a b c d e f g h i j k l m Barros L, et al. Phenolic profiles of cultivated, in vitro cultured and commercial samples of Melissa officinalis L. infusions. Food Chem. (2013)
  11. ^ Sanchez-Medina A, et al. Comparison of rosmarinic acid content in commercial tinctures produced from fresh and dried lemon balm (Melissa officinalis). J Pharm Pharm Sci. (2007)
  12. ^ a b c A New Antioxidative 1,3-Benzodioxole from Melissa officinalis.
  13. ^ a b c d e Spiridon I, et al. Antioxidant capacity and total phenolic contents of oregano (Origanum vulgare), lavender (Lavandula angustifolia) and lemon balm (Melissa officinalis) from Romania. Nat Prod Res. (2011)
  14. ^ Melitric acids A and B, new trimeric caffeic acid derivatives from Melissa officinalis.
  15. ^ Ziaková A, Brandsteterová E, Blahová E. Matrix solid-phase dispersion for the liquid chromatographic determination of phenolic acids in Melissa officinalis. J Chromatogr A. (2003)
  16. ^ Patora J, Klimek B. Flavonoids from lemon balm (Melissa officinalis L., Lamiaceae). Acta Pol Pharm. (2002)
  17. ^ Heitz A, et al. Luteolin 3'-glucuronide, the major flavonoid from Melissa officinalis subsp. officinalis. Fitoterapia. (2000)
  18. ^ Hohmann J, et al. Protective effects of the aerial parts of Salvia officinalis, Melissa Officinalis and Lavandula angustifolia and their constituents against enzyme-dependent and enzyme-independent lipid peroxidation. Planta Med. (1999)
  19. ^ Zábranská M, et al. Analysis of plant galactolipids by reversed-phase high-performance liquid chromatography/mass spectrometry with accurate mass measurement. Chem Phys Lipids. (2012)
  20. ^ a b c d e f g Chung MJ, et al. Anti-diabetic effects of lemon balm ( Melissa officinalis) essential oil on glucose- and lipid-regulating enzymes in type 2 diabetic mice. Br J Nutr. (2010)
  21. ^ a b c d Pereira RP, et al. Antioxidant effects of different extracts from Melissa officinalis, Matricaria recutita and Cymbopogon citratus. Neurochem Res. (2009)
  22. ^ The aromatic and polyphenolic composition of lemon balm (Melissa officinalis L. subsp. officinalis) tea.
  23. ^ a b Awad R, et al. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother Res. (2009)
  24. ^ a b Yoo DY, et al. Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus. Neurochem Res. (2011)
  25. ^ a b Cases J, et al. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Med J Nutrition Metab. (2011)
  26. ^ Ibarra A, et al. Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice. Phytomedicine. (2010)
  27. ^ Taiwo AE, et al. Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender. Indian J Pharmacol. (2012)
  28. ^ Komiya M, Takeuchi T, Harada E. Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice. Behav Brain Res. (2006)
  29. ^ Wetherell MA, Hyland ME, Harris JE. Secretory immunoglobulin A reactivity to acute and cumulative acute multi-tasking stress: relationships between reactivity and perceived workload. Biol Psychol. (2004)
  30. ^ The use of analogue scales in rating subjective feelings.
  31. ^ a b Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. (2004)
  32. ^ Dimpfel W, Pischel I, Lehnfeld R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activity of volunteers. Eur J Med Res. (2004)
  33. ^ a b EUROPEAN HERBS WITH CHOLINERGIC ACTIVITIES: POTENTIAL IN DEMENTIA THERAPY.
  34. ^ Wake G, et al. CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. J Ethnopharmacol. (2000)
  35. ^ a b c Kennedy DO, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav. (2002)
  36. ^ Neuroprotective Properties of Melissa Officinalis L. Extract Against Ecstasy-Induced Neurotoxicity.
  37. ^ Guginski G, et al. Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice. Pharmacol Biochem Behav. (2009)
  38. ^ a b Mazzanti G, et al. Inhibitory activity of Melissa officinalis L. extract on Herpes simplex virus type 2 replication. Nat Prod Res. (2008)
  39. ^ Zeraatpishe A, et al. Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation. Toxicol Ind Health. (2011)
  40. ^ Encalada MA, et al. Anti-proliferative effect of Melissa officinalis on human colon cancer cell line. Plant Foods Hum Nutr. (2011)
  41. ^ Awad R, et al. Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system. Can J Physiol Pharmacol. (2007)

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