Melissa

The drug is the fresh or dried aerial parts, especially the leaf. It is prepared as a tea, tincture, glycerite, fresh-plant extract or infused honey.

Western practice uses melissa as a calming nervine, mild sedative, carminative, antiviral and antispasmodic ^{28Reference 28Shakeri A et al. · 2016ReviewMelissa officinalis L. — a review of its traditional uses, phytochemistry and pharmacology}. Its indications include anxiety, insomnia, low mood, nervous palpitations, indigestion, gas, nausea, colds, headaches and stress-related digestive complaints.

European herbalists valued it as a “gladdening” herb for melancholy and nervous exhaustion. It was a defining ingredient of aromatic cordials such as Carmelite water ^{28Reference 28Shakeri A et al. · 2016ReviewMelissa officinalis L. — a review of its traditional uses, phytochemistry and pharmacology}.

Today the EU recognises its traditional use for mild symptoms of mental stress, to aid sleep, and for mild digestive complaints including bloating and flatulence ^{29Reference 29European Medicines Agency · 2013ReviewCommunity herbal monograph on Melissa officinalis L., folium (EMA/HMPC/196745/2012) — regulatory monograph. https://www.ema.europa.eu/en/documents/herbal-monograph/final-community-herbal-monograph-melissa-officinalis-l-folium_en.pdfView study →}.

In practice it is rarely given alone. For calming it is combined with passionflower, skullcap, valerian, chamomile, lavender or oats, and for digestion with peppermint, fennel, ginger or chamomile.

In Traditional Iranian Medicine lemon balm is commonly used for heart palpitations ^{24Reference 24Alijaniha F et al. · 2015RCTHeart palpitation relief with Melissa officinalis leaf extract — double-blind randomised placebo-controlled trialView study →}.

In Iranian folk medicine the leaf is used for digestive and functional bowel complaints, and as a carminative, antispasmodic, sedative, analgesic, tonic and diuretic ^{10Reference 10Miraj S et al. · 2017ReviewMelissa officinalis L: a review study with an antioxidant prospective — reviewView study →}.

A 2021 systematic review and meta-analysis of clinical trials found lemon balm reduced anxiety scores more than placebo (SMD −0.98, 95% CI −1.63 to −0.33). The effect was clearest in acute settings, and no serious side effects were reported. The trials varied widely, and the authors advise caution ^{1Reference 1Ghazizadeh J et al. · 2021Meta-analysisThe effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials — a systematic review and meta-analysisView study →}.

A 15-day open-label pilot of a standardised extract (Cyracos, which contains rosmarinic acid) reported an 18% drop in anxiety, and 14 of 20 volunteers reached full remission of anxiety. There was no placebo arm ^{2Reference 2Cases J et al. · 2011Clinical trialPilot trial of Melissa officinalis L. leaf extract in mild-to-moderate anxiety disorders and sleep disturbances — open-label clinical trialView study →}.

In placebo-controlled crossover trials in healthy volunteers, a single 300 mg dose of a standardised extract raised self-rated calmness at the earliest time points, and 600 mg improved accuracy of attention ^{4Reference 4Kennedy DO et al. · 2002RCTModulation of mood and cognitive performance following acute administration of Melissa officinalis — randomised placebo-controlled crossover trialView study →}.

A combination of lemon balm and valerian, at its lowest dose of 600 mg, reduced anxiety during a laboratory stress test. The highest dose, 1800 mg, raised anxiety in one testing session ^{5Reference 5Kennedy DO et al. · 2006RCTAnxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory-induced stress — randomised placebo-controlled crossover trialView study →}.

Rosmarinic acid and the triterpenes ursolic acid and oleanolic acid inhibit GABA transaminase, the enzyme that breaks down GABA, in vitro ^{7Reference 7Awad R et al. · 2009In vitroBioassay-guided fractionation of lemon balm using an in vitro measure of GABA transaminase activity — in vitroView study →}. A standardised extract reduced anxiety-like behaviour in mice in a dose-dependent way ^{6Reference 6Ibarra A et al. · 2010AnimalEffects of chronic administration of Melissa officinalis extract on anxiety-like reactivity in mice — animal modelView study →}.

Gap: trials are small and use different standardized extracts; the dose-response is non-linear (higher is not better), and few studies measure physiological stress markers.

The same 2021 meta-analysis found a smaller reduction in depression scores than placebo (SMD −0.47, 95% CI −0.73 to −0.21) ^{1Reference 1Ghazizadeh J et al. · 2021Meta-analysisThe effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials — a systematic review and meta-analysisView study →}.

In a 12-week trial in people with type 2 diabetes and depressive symptoms, 700 mg a day of hydroalcoholic extract reduced Beck depression and anxiety scores more than placebo. Sleep quality, fasting blood sugar and hs-CRP did not differ between groups ^{8Reference 8Safari M et al. · 2023RCTThe effects of Melissa officinalis on depression and anxiety in type 2 diabetes patients with depression — randomised double-blind placebo-controlled trialView study →}.

In an 8-week trial in 80 people with chronic stable angina, 3 g a day of lemon balm reduced depression, anxiety and stress (DASS-21) scores and sleep disturbance compared with placebo ^{9Reference 9Haybar H et al. · 2018RCTThe effects of Melissa officinalis supplementation on depression, anxiety, stress and sleep disorder in patients with chronic stable angina — randomised placebo-controlled trialView study →}.

Gap: effect sizes are modest, samples small, and both dedicated RCTs studied medically ill populations rather than primary depression; heterogeneity across trials was high.

The leaf’s antioxidant activity comes from its phenolic compounds, chiefly rosmarinic acid, with caffeic and chlorogenic acids and luteolin flavonoids ^{10Reference 10Miraj S et al. · 2017ReviewMelissa officinalis L: a review study with an antioxidant prospective — reviewView study →}.

In the angina trial, 3 g a day of powdered leaf for 8 weeks lowered serum malondialdehyde, a marker of lipid damage, and raised paraoxonase-1 activity compared with placebo ^{11Reference 11Javid AZ et al. · 2018RCTThe effects of Melissa officinalis in chronic stable angina on serum biomarkers of oxidative stress, inflammation and lipid profile — randomised placebo-controlled trialView study →}.

The rest of the evidence is in vitro and review-level, measuring the radical-scavenging capacity of extracts. No change in an antioxidant marker has been linked to a clinical outcome.

A 2020 meta-analysis of seven RCTs found lemon balm lowered total cholesterol (SMD −0.26) and systolic blood pressure (SMD −0.56). It found no significant change in triglycerides, LDL, HDL, diastolic pressure, hs-CRP, fasting glucose, HbA1c or insulin ^{12Reference 12Heshmati J et al. · 2020Meta-analysisEffects of Melissa officinalis on cardio-metabolic outcomes — systematic review and meta-analysisView study →}.

In people with borderline high cholesterol, 1000 mg of leaf powder three times a day for two months lowered LDL compared with placebo. Total cholesterol did not change ^{13Reference 13Jandaghi P et al. · 2016RCTLemon balm — a promising herbal therapy for patients with borderline hyperlipidemia — randomised double-blind placebo-controlled trialView study →}.

In the 8-week angina trial, triglycerides, total and LDL cholesterol and hs-CRP fell, and HDL rose ^{11Reference 11Javid AZ et al. · 2018RCTThe effects of Melissa officinalis in chronic stable angina on serum biomarkers of oxidative stress, inflammation and lipid profile — randomised placebo-controlled trialView study →}.

The meta-analysis authors note a small number of studies and a serious risk of bias ^{12Reference 12Heshmati J et al. · 2020Meta-analysisEffects of Melissa officinalis on cardio-metabolic outcomes — systematic review and meta-analysisView study →}.

Gap: pooled effects are small and rest on a handful of high-risk-of-bias trials, mostly from a few centers; no hard cardiovascular outcomes have been measured.

A double-blind, placebo-controlled trial tested a 1% cream of a 70:1 dried-leaf extract (Lo-701) in 66 people with recurrent cold sores. Applied four times a day for five days, it lowered the combined symptom score on day 2, when symptoms usually peak ^{15Reference 15Koytchev R et al. · 1999RCTBalm mint extract (Lo-701) for topical treatment of recurring herpes labialis — randomised placebo-controlled trialView study →}.

In vitro, an aqueous extract acted directly on free herpes simplex virus particles, including acyclovir-resistant strains, and blocked their attachment to and entry into cells. It had no effect once the virus was inside the cell. Rosmarinic acid accounted for much of the activity ^{16Reference 16Astani A et al. · 2014In vitroAttachment and penetration of acyclovir-resistant herpes simplex virus are inhibited by Melissa officinalis extract — in vitroView study →}.

The essential oil inhibited herpes simplex type 2 in cell culture ^{17Reference 17Allahverdiyev A et al. · 2004In vitroAntiviral activity of the volatile oils of Melissa officinalis against Herpes simplex virus type-2 — in vitroView study →}, and other extracts inactivated type 1 virus ^{18Reference 18Dimitrova Z et al. · 1993In vitroAntiherpes effect of Melissa officinalis L. extracts — in vitroView study →}.

Gap: only one modest topical RCT exists; the effect is preparation-specific to concentrated creams, and there is no evidence for oral lemon balm against herpes.

In the open-label Cyracos pilot, insomnia scores fell by 42% over 15 days ^{2Reference 2Cases J et al. · 2011Clinical trialPilot trial of Melissa officinalis L. leaf extract in mild-to-moderate anxiety disorders and sleep disturbances — open-label clinical trialView study →}. A placebo-controlled trial of lemon balm combined with Nepeta menthoides improved insomnia severity, anxiety and depression in people with insomnia ^{19Reference 19Ranjbar M et al. · 2018RCTEffects of herbal combination (Melissa officinalis L. and Nepeta menthoides) on insomnia severity, anxiety and depression in insomniacs — randomised placebo-controlled trialView study →}.

In the angina trial, lemon balm reduced sleep disturbance ^{9Reference 9Haybar H et al. · 2018RCTThe effects of Melissa officinalis supplementation on depression, anxiety, stress and sleep disorder in patients with chronic stable angina — randomised placebo-controlled trialView study →}. In the diabetes trial, sleep quality did not differ from placebo ^{8Reference 8Safari M et al. · 2023RCTThe effects of Melissa officinalis on depression and anxiety in type 2 diabetes patients with depression — randomised double-blind placebo-controlled trialView study →}.

Gap: little placebo-controlled evidence for lemon balm alone; the strongest sleep signals come from open-label or multi-herb designs.

Acute crossover trials in healthy young adults show effects that depend on the dose and the timing.

A single 1600 mg dose of a dried leaf with cholinergic receptor-binding activity improved memory and calmness at every time point. Lower doses slowed timed memory tasks ^{3Reference 3Kennedy DO et al. · 2003RCTModulation of mood and cognitive performance following single doses of Melissa officinalis with CNS nicotinic and muscarinic receptor-binding properties — randomised placebo-controlled crossover trialView study →}.

With a different standardised extract, 600 mg improved accuracy of attention, and 900 mg reduced alertness at every time point ^{4Reference 4Kennedy DO et al. · 2002RCTModulation of mood and cognitive performance following acute administration of Melissa officinalis — randomised placebo-controlled crossover trialView study →}.

A four-month RCT in 42 people with mild-to-moderate Alzheimer’s disease found that 60 drops a day of extract improved cognition on the ADAS-cog scale compared with placebo. Agitation was more common in the placebo group ^{20Reference 20Akhondzadeh S et al. · 2003RCTMelissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease — randomised double-blind placebo-controlled trialView study →}.

The aromatherapy trials for agitation in dementia are mixed. An early trial of the essential oil was positive ^{22Reference 22Ballard CG et al. · 2002RCTAromatherapy for the management of agitation in severe dementia — randomised double-blind placebo-controlled trial with MelissaView study →}. A larger, rigorously blinded trial comparing melissa oil, donepezil and placebo found no difference between the three ^{21Reference 21Burns A et al. · 2011RCTA double-blind placebo-controlled randomised trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer’s diseaseView study →}, and a later essential-oil trial found no benefit over placebo ^{23Reference 23Watson K et al. · 2019RCTA randomised controlled trial of Lavender and Lemon Balm essential oils for agitated behaviour in older people with and without dementiaView study →}.

Gap: acute effects are inconsistent and dose-sensitive; the one positive AD trial is small and unreplicated, and the best-blinded aromatherapy trial was null.

In the angina trial, 3 g a day of lemon balm lowered high-sensitivity C-reactive protein (hs-CRP) along with oxidative-stress markers ^{11Reference 11Javid AZ et al. · 2018RCTThe effects of Melissa officinalis in chronic stable angina on serum biomarkers of oxidative stress, inflammation and lipid profile — randomised placebo-controlled trialView study →}. One type 2 diabetes trial also reported lower hs-CRP than placebo ^{14Reference 14Asadi A et al. · 2019RCTEfficacy of Melissa officinalis extract on glycemic control and cardiovascular risk factors in type 2 diabetes — randomised double-blind clinical trialView study →}.

A second diabetes trial found no difference in hs-CRP ^{8Reference 8Safari M et al. · 2023RCTThe effects of Melissa officinalis on depression and anxiety in type 2 diabetes patients with depression — randomised double-blind placebo-controlled trialView study →}, and the cardiometabolic meta-analysis found no significant pooled effect on hs-CRP ^{12Reference 12Heshmati J et al. · 2020Meta-analysisEffects of Melissa officinalis on cardio-metabolic outcomes — systematic review and meta-analysisView study →}.

The clinical evidence is a few small trials measuring one inflammatory marker, with no disease endpoint tested.

A double-blind, placebo-controlled trial tested 500 mg of freeze-dried aqueous leaf extract twice a day for 14 days in adults with benign palpitations. Of 71 people recruited, 55 completed it. The extract reduced the frequency of palpitation episodes and the number of anxious patients compared with placebo, with no serious side effects ^{24Reference 24Alijaniha F et al. · 2015RCTHeart palpitation relief with Melissa officinalis leaf extract — double-blind randomised placebo-controlled trialView study →}.

Gap: a single small trial in benign (non-arrhythmic) palpitations; outcomes were patient-reported, and there is no evidence for organic arrhythmias.

A 12-week randomised, double-blind trial in 62 people with type 2 diabetes found 700 mg a day of hydroalcoholic extract improved fasting blood sugar, HbA1c, β-cell activity, triglycerides, HDL, hs-CRP and systolic blood pressure compared with placebo, with no adverse effects ^{14Reference 14Asadi A et al. · 2019RCTEfficacy of Melissa officinalis extract on glycemic control and cardiovascular risk factors in type 2 diabetes — randomised double-blind clinical trialView study →}.

A second 12-week trial of the same dose in people with diabetes and depression found no difference in fasting blood sugar ^{8Reference 8Safari M et al. · 2023RCTThe effects of Melissa officinalis on depression and anxiety in type 2 diabetes patients with depression — randomised double-blind placebo-controlled trialView study →}. The cardiometabolic meta-analysis found no significant pooled effect on fasting glucose or HbA1c ^{12Reference 12Heshmati J et al. · 2020Meta-analysisEffects of Melissa officinalis on cardio-metabolic outcomes — systematic review and meta-analysisView study →}.

Gap: a single positive RCT against a null pooled meta-analytic result for glucose; needs replication before the antidiabetic claim is firm.

Lemon balm is used traditionally for nervous indigestion, gas and cramping. Its essential oil contains citral, made up of geranial and neral, along with citronellal.

Most clinical data come from multi-herb digestive formulas that include lemon balm, rather than from lemon balm alone.

Side effects. The most common side effect is mild drowsiness. Stomach upset or an allergic reaction is rare, and no serious adverse events were reported across the clinical meta-analyses ^{1,12Reference 1Ghazizadeh J et al. · 2021Meta-analysisThe effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials — a systematic review and meta-analysisView study →Reference 12Heshmati J et al. · 2020Meta-analysisEffects of Melissa officinalis on cardio-metabolic outcomes — systematic review and meta-analysisView study →}. The EMA lists no known side effects for the traditional preparations ^{29Reference 29European Medicines Agency · 2013ReviewCommunity herbal monograph on Melissa officinalis L., folium (EMA/HMPC/196745/2012) — regulatory monograph. https://www.ema.europa.eu/en/documents/herbal-monograph/final-community-herbal-monograph-melissa-officinalis-l-folium_en.pdfView study →}.

Drowsiness and sedatives. The EMA notes that lemon balm may impair the ability to drive or use machines ^{29Reference 29European Medicines Agency · 2013ReviewCommunity herbal monograph on Melissa officinalis L., folium (EMA/HMPC/196745/2012) — regulatory monograph. https://www.ema.europa.eu/en/documents/herbal-monograph/final-community-herbal-monograph-melissa-officinalis-l-folium_en.pdfView study →}. Its calming action may add to that of sedatives, sleep medicines, alcohol and other calming herbs. This is inferred from its pharmacology; no interaction trials have been done, and the EMA records no interaction data ^{29Reference 29European Medicines Agency · 2013ReviewCommunity herbal monograph on Melissa officinalis L., folium (EMA/HMPC/196745/2012) — regulatory monograph. https://www.ema.europa.eu/en/documents/herbal-monograph/final-community-herbal-monograph-melissa-officinalis-l-folium_en.pdfView study →}.

Thyroid. Freeze-dried leaf extracts reduce the binding of TSH and Graves’ antibodies to the thyroid receptor in vitro ^{25Reference 25Auf’mkolk M et al. · 1985In vitroExtracts and auto-oxidised constituents of certain plants inhibit the receptor-binding and biological activity of Graves’ immunoglobulins — in vitroView study →}. The EMA notes that the water extract may inhibit TSH in laboratory and animal studies, and that the clinical relevance is not known ^{29Reference 29European Medicines Agency · 2013ReviewCommunity herbal monograph on Melissa officinalis L., folium (EMA/HMPC/196745/2012) — regulatory monograph. https://www.ema.europa.eu/en/documents/herbal-monograph/final-community-herbal-monograph-melissa-officinalis-l-folium_en.pdfView study →}. High or prolonged doses are best used with care in hypothyroidism or alongside thyroid medication.

Children. The EMA does not recommend lemon balm for children under 12, because there are not enough data ^{29Reference 29European Medicines Agency · 2013ReviewCommunity herbal monograph on Melissa officinalis L., folium (EMA/HMPC/196745/2012) — regulatory monograph. https://www.ema.europa.eu/en/documents/herbal-monograph/final-community-herbal-monograph-melissa-officinalis-l-folium_en.pdfView study →}.