A 2022 review "The Properties of Melissa officinalis L" published in Front Biosci (Schol Ed) by Wissam Zam, Cristina Quispe, Javad Sharifi-Rad, María Dolores López, Mauricio Schoebitz, Miquel Martorell, Farukh Sharopov, Patrick Valere Tsouh Fokou, Abhay Prakash Mishra, Deepak Chandran, Manoj Kumar, Jen-Tsung Chen, Raffaele Pezzani, aimed that Melissa officinalis is a plant known in numerous countries for its medicinal activities. This plant has been used since ancient times to treat different disorders, including gastrointestinal, cardiovascular, neurological, psychological conditions. Melissa officinalis contains several phytochemicals such as phenolic acids, flavonoids, terpenoids, and many others at the basis of its pharmacological activities. Indeed, the plant can have antioxidant, anti-inflammatory, antispasmodic, antimicrobial, neuroprotective, nephroprotective, antinociceptive effects. Given its consolidated use, Melissa officinalis has also been experimented with clinical settings, demonstrating interesting properties against different human diseases, such as anxiety, sleeping difficulties, palpitation, hypertension, depression, dementia, infantile colic, bruxism, metabolic problems, Alzheimer's disease, and sexual disorders. As for any natural compound, drug, or plant extract, also Melissa officinalis can have adverse effects, even though the reported events are very rare and the plant can be considered substantially safe. This review has been prepared with a specific research strategy, interrogating different databases with the keyword Melissa officinalis. Moreover, this work analyzes the properties of this plant updating currently available literature, with a special emphasis on human studies.

Aromatherapy with Lemon Balm was more effective than with Lavender essential oil at reducing agitation but less at helping with irritability in a trial on 49 elderly people.

Another study also demonstrated that chronic administration of Lemon Balm relieved stress-related effects. Further studies should incorporate a placebo and investigate physiological stress markers.

A 2014 randomized controlled trial "Anti-stress effects of Lemon Balm-containing foods" published in Nutrients by Andrew Scholey, Amy Gibbs, Chris Neale, Naomi Perry, Anastasia Ossoukhova, Vanessa Bilog, Marni Kras, Claudia Scholz, Mathias Sass, Sybille Buchwald-Werner, administered Lemon Balm as a water based drink, which confirmed absorption of rosmarinic acid effects on mood and cognitive function, we conducted two similar double-blind, placebo-controlled, crossover studies. These evaluated the mood and cognitive effects of a standardised Melissa officinalis preparation administered in palatable forms in a beverage and in yoghurt. In each study a cohort of healthy young adults' self-rated aspects of mood were measured before and after a multi-tasking framework (MTF) administered one hour and three hours following one of four treatments. Both active Lemon Balm treatments were generally associated with improvements in mood and/or cognitive performance, though there were some behavioral "costs" at other doses and these effects depended to some degree on the delivery matrix. According to the results, a sweetened water-based drink containing 0.3 grams of Lemon Balm extract reduced stress and improved mood in a group of 25 healthy young adults, compared to a placebo. The results were confirmed by repeating the test with yogurt instead of water in the same study. Participants felt the stress-reducing effects within one to three hours after eating the yogurt.

A 2004 study found that taking Lemon Balm eased the negative mood effects of laboratory-induced psychological stress. Participants who took Lemon Balm self-reported an increased sense of calmness and reduced feelings of alertness. Although this was a double-blind, placebo-controlled study, it had a small sample size of 18 people. Further research is needed to elaborate on these findings.

Take 300 mg of Lemon Balm in capsule form twice a day. You can take a single dose of 600 mg in acute episodes of stress.

A mix of Lemon Balm, Valerian, Passionflower, and Butterbur extracts reduced acute stress in a trial on 72 healthy people. Taken together, limited evidence suggests that Lemon Balm helps with stress. Further research is needed to confirm these results and investigate how to use Lemon Balm therapeutically.

In a pilot trial Lemon Balm completely eliminated anxiety in 14 people with stress. Also, a combination of Lemon Balm and Valerian root significantly reduced anxiety in 24 healthy volunteers.

The intake of 600 mg of Lemon Balm reduces stress levels and induces a sense of calmness in the body according to a study. Lemon Balm contains a compound called rosmarinic acid which lowers the symptoms of anxiety-like excitement and nervousness. Foods containing Lemon Balm has a positive effect on your mood which reduces stress and anxiety as well. Larger human studies should be conducted to confirm these results.

In another study Lemon Balm extract was given at a dose of 300 mg twice daily to a group of stressed people with mild-to-moderate anxiety and sleep disturbances. A combination of Lemon Balm and Valerian root significantly reduced anxiety in 24 healthy volunteers. This study found that Lemon Balm reduced anxiety by 18%, reduced stress-associated symptoms by 15% and lowered insomnia by 42%. Although this is promising, more research is needed to truly determine its efficacy.

Research published in 2014 examined the mood and cognitive effects of foods containing Lemon Balm. The supplement was mixed into a beverage and into yogurt along with either natural or artificial sweeteners. Participants in both groups reported positive effects on various aspects of mood, including reduced levels of anxiety.

A 2013 review from The University of Melbourne of plant-based medicines that included 53 species supports the efficacy of the chronic use (i.e., greater than one day) of Lemon Balm in the treatment of anxiety disorders. It concluded that current evidence supports acute anxiolytic activity in Lemon Balm.

Melissa oil has also been shown to modulate mood and cognitive performance in healthy young volunteers, who reported no side effects or symptoms of toxicity. Even at the lowest doses, self-rated “calmness” was elevated with melissa oil treatment, making it a great essential oil for depression.

A 2021 systematic review and meta-analysis "The effects of Lemon Balm (Melissa officinalis L.) on depression and anxiety in clinical trials" published in Phytother Res by Javid Ghazizadeh, Saeed Sadigh-Eteghad, Wolfgang Marx, Ali Fakhari, Sanaz Hamedeyazdan, Mohammadali Torbati, Somaiyeh Taheri-Tarighi, Mostafa Araj-Khodaei, Mojgan Mirghafourvand, were considered to investigate the effects of Lemon Balm as a medicinal herb on anxiety and depression in clinical trials and its side effects. All randomized clinical trials published up to October 30, 2020 that examined Lemon Balm in patients with symptoms of depression or anxiety, with acute or chronic manifestations, were searched in 12 online databases. Statistical analysis was performed using RevMan software. Continuous data were analyzed using standardized mean differences. Statistical heterogeneity was assessed using Chi2 , I2 , and p value tests. Based on meta-analysis results, Lemon Balm significantly improved mean anxiety and depression scores compared with the placebo (SMD: -0.98; 95% CI: -1.63 to -0.33; p = 0.003), (SMD: -0.47; 95% CI: -0.73 to -0.21, p = 0.0005) respectively, without serious side effects. Current evidence suggests that Lemon Balm may be effective in improving anxiety and depressive symptoms, particularly in the acute setting. Due to the high level of heterogeneity between studies, results should be interpreted with caution. The small number of clinical trials and differences between their methods were the limitations of the present study. Further high-quality studies are needed to firmly establish the clinical efficacy of the Lemon Balm.

Another 2020 study "Melissa officinalis L. hydro-alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis" published in Exp Physiol. by Javid Ghazizadeh, Sanaz Hamedeyazdan, Mohammadali Torbati, Fereshteh Farajdokht, Ali Fakhari, Javad Mahmoudi, Mostafa Araj-Khodaei, Saeed Sadigh-Eteghad, evaluated the effects of a hydro-alcoholic extract of Melissa officinalis (HAEMO) on anxiety- and depressive-like behaviours, oxidative stress and apoptosis markers in restraint stress-exposed mice. In order to induce a depression-like model, mice were subjected to restraint stress (3 h day^-1 for 14 days) and received normal saline or HAEMO (50, 75 and 150 mg kg^-1 day^-1) for 14 days. The administered doses of HAEMO were designated based on the concentration of one of the main phenolic compounds present in the extract, rosmarinic acid (2.55 mg kg^-1 at lowest dose); other phytochemical analyses including assays for antioxidant activity, total phenols and flavonoids were also carried out. The behavioural changes in an open field task, elevated plus maze, tail suspension and forced swimming tests were evaluated. Also, malondialdehyde levels and enzyme activities of superoxide dismutase and glutathione peroxidase, and total antioxidant capacity were assessed in the prefrontal cortex and hippocampus. Moreover, levels of Bcl-2, Bax and caspase 3 in the brain as well as serum concentration of corticosterone were evaluated. HAEMO (75 and 150 mg kg^-1 ) significantly reversed anxiety- and depressive-like behaviours. Also, HAEMO reduced MDA levels, enhanced enzymatic antioxidant activities and restored serum levels of corticosterone. An immunoblotting analysis also demonstrated that HAEMO decreased levels of pro-apoptotic markers and increased anti-apoptotic protein levels in the prefrontal cortex and hippocampus of restraint stress-exposed mice. Our findings suggested that HAEMO reduced inflammation and had anxiolytic and antidepressant effects in mice.

A 2013 study conducted at the University of Melbourne found that the effects of Melissa essential oil were shown to help improve anxiety, depression, neuroprotectivity and cognition.

Melissa essential oil has also been shown to modulate mood and cognitive performance in healthy young volunteers, who reported no side effects or symptoms of toxicity. Even at the lowest doses, self-rated “calmness” was elevated with melissa oil treatment, making it a great essential oil for improve mood. Research has shown that a dose of 600 mg per day resulted in reduced negative mood effects and increase self-ratings of calmness.

In another study Lemon Balm improved cognitive performance and mood in 20 healthy participants. Lemon Balm also increased accuracy and attention in cognitive performance tasks in 20 college students.

Research in 2021 suggests that Lemon Balm may benefit mood and cognitive performance. The study demonstrated that treatment with Lemon Balm led to improvements in tasks involving memory, concentration, and mathematics. The findings suggest that Lemon Balm may be effective in improving anxiety and symptoms of depression in some people. However, the researchers note that further high quality studies are needed to firmly establish the clinical efficacy of the Lemon Balm. These findings also relate to Lemon Balm supplements, not Lemon Balm tea.

A study investigating 300 mg of Lemon Balm extract supplementation on stress and cognitive function found that 300 mg significantly improved maths performance alertness and immediate recall compared to baseline.

In another study of Lemon Balm at Northumbria University in England students were tested for weeks while using either Lemon Balm or a placebo. The students did significantly better on the tests after taking Lemon Balm and continued to post improved scores for up to six hours after taking the herb. The students taking Lemon Balm were noted to be calmer and less stressed during the tests.

A 2014 study also looked at the effects of Lemon Balm in improving cognitive function. Participants were asked to do cognitive tasks involving memory, mathematics, and concentration. The results of these computerized tasks suggest that participants who ingested Lemon Balm performed better than those who didn’t.

A 2013 study conducted at The University of Melbourne found that the effects of Melissa essential oil were shown to help improve anxiety, depression, neuroprotectivity and cognition. Lemon Balm improved cognitive performance and memory in 2 small trials on 23 healthy people. Similarly, Lemon Balm improved cognitive performance and mood in 20 healthy participants. Lemon Balm also increased accuracy and attention in cognitive performance tasks in 20 college students.

One study showed an oral dose taken daily for four months appeared to help reduce agitation and decrease symptoms of agitation in those with mild to moderate Alzheimer’s disease. Lemon Balm may also help address other mental health concerns as well, including attention deficit-hyperactivity disorder (ADHD), although more research is needed.

Animal studies show that, when provided shortly after such an episode, Lemon Balm appears to be protective of the brain.

In one study Lemon Balm improved performance and memory in healthy participants. It extracts impacts on receptor binding properties, which in turn, have shown benefit for improved cognitive effects such as alertness and memory.

A 2021 study "The effect of Melissa officinalis L. extract on learning and memory" published in Journal Ethnopharmacol by Mohsen Naseri, Reza Arabi Mianroodi, Zeynab Pakzad, Peyman Falahati, Masomeh Borbor, Hossein Azizi, Sima Nasri, was to evaluate the impact of the hydroalcoholic extract of Melissa officinalis L. on learning and memory, considering its impact on nitric oxide synthase and brain-derived neurotrophic factor expression in the hippocampus of diabetic rats. Rutin was main flavonoid compound and rosmarinic acid was the main phenolic compound of the Melissa officinalis extract. Streptozotocin induced diabetes and impaired learning and memory in diabetic rats. Melissa officinalis treated-control group showed a higher alternation score in the Y-maze task and step-through latency in the passive avoidance task compared to the vehicle treated diabetic group. Melissa officinalis-treated rats showed a higher alternation score in the Y-maze task in all doses compared to the vehicle treated diabetic group (P < 0.05). In addition, in the passive avoidance task Melissa officinalis increased step-through latency (P < 0.05) but not initial latency, in all doses. Furthermore, in diabetic rats, the expression of brain-derived neurotrophic factor and nitric oxide synthase genes decreased. However, hippocampal brain-derived neurotrophic factor and nitric oxide synthase gene expression was increased in Melissa officinalis-treated rats compared to diabetic rats (P < 0.05). Melissa officinalis improved learning and memory in diabetic rats, which may have occurred by increasing brain-derived neurotrophic factor and nitric oxide synthase gene expression.

"A randomised double-blind placebo-controlled pilot trial of a combined extract of sSage, Rosemary and Melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age" published in Phytomedicine in 2018 by N S L Perry, R Menzies, F Hodgson, P Wedgewood, M-J R Howes, H J Brooker, K A Wesnes, E K Perry, of 44 normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed.

According to a study, patients with mild to moderate Alzheimer's disease who took Lemon Balm daily for 4 months improved their cognitive function. Lemon Balm herb also improved cognitive tasks which involved memory, concentration and mathematics in participants as compared to those who didn't ingest the herb.

A 2023 randomized placebo-controlled double-blind trial "Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia" published in Journal Alzheimers Dis., by Moeko Noguchi-Shinohara, Tsuyoshi Hamaguchi, Kenji Sakai, Junji Komatsu, Kazuo Iwasa, Mai Horimoto, Hiroyuki Nakamura, Masahito Yamada, Kenjiro Ono, aimed to assess the effects of M. officinalis extract on cognition in older adults without dementia. This study included individuals who were diagnosed with subjective or mild cognitive impairment (n = 323). The trial involved M. officinalis extract supplementation (500 mg of RA per day) period of 96 weeks followed by a washout period of 24 weeks. The primary endpoint was the Alzheimer's Disease Assessment Scale-cognitive subscale score, and the secondary endpoints were other cognitive measure results as well as safety and tolerability. There were no significant differences in cognitive measures between the placebo and M. officinalis groups from baseline to 96 weeks. However, based on the analysis of Clinical Dementia Rating Sum of Boxes scores in participants without hypertension, the score was found to be increased by 0.006 and decreased by 0.085 in the M. officinalis and placebo groups, respectively; this difference was statistically significant (p = 0.036). Furthermore, there were no differences in vital signs, physical and neurological measures, or hippocampal volume between the two groups. These results indicate that M. officinalis extract may help prevent cognitive decline in older adults without hypertension.

A 2022 study "Attenuation of neuroinflammation in microglia cells by extracts with high content of rosmarinic acid from in vitro cultured Melissa officinalis L. cells" published in Journal Pharm Biomed Anal., by Vittoria Borgonetti, Giovanna Pressi, Oriana Bertaiola, Chiara Guarnerio, Manuela Mandrone, Ilaria Chiocchio, Nicoletta Galeotti, evaluate the anti-inflammatory and neuroprotective activity of a standardized Melissa officinalis L. phytocomplex extract (MD) obtained with an in vitro plant cell culture. The MD has been chemically characterized and the content of total polyphenols was 5.17 ± 0.1 % w/w, with a content of rosmarinic acid (RA), its main constituent, of 4.02 ± 0.1 % w/w. MD was tested in an in vitro model of neuroinflammation, in which microglia cells (BV2) were stimulated with Lipopolysaccharides (LPS; 250 ng/mL) for 24 h and its pharmacological activity was compared with that of RA. MD (10 µg/mL) and RA (0.4 μg/mL) reduced pro-inflammatory factors (NF-kB, HDAC, IL-1ß) in LPS-stimulated BV2 cells and counteracted the toxic effect produced by activated microglia medium on neuronal cells. This work shows the efficacy of MD on reducing microglia-mediated neuroinflammation and promoting neuroprotection, highlighting the innovative use of in vitro plant cell cultures to obtain contaminant-free extracts endowed with marked activity and improved quali-quantitative ratio in the constituents' content.
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A small but interesting study used Lemon Balm, aromatherapeutically to calm overexcited individuals suffering from dementia.

A study in the Journal of Complimentary Medicine shows that the Melissa essential oil treats the agitation in severe dementia. A drop of Melissa oil should be rubbed by placing it between the palms, breathe for 30 seconds by making a cup over the nose and mouth.

In one study, researchers found that using Lemon Balm also improved memory and lengthened attention span in individuals suffering from Alzheimer's disease. This effect may be due to its content of antioxidants, which are thought to protect body cells from damage caused by a chemical process called oxidation.

Scientists at Newcastle General Hospital’s Institute for Aging and Health conducted a placebo-controlled trial to determine the value of Melissa essential oil for agitation in people with severe dementia, which is a frequent and major management problem, especially for patients with severe cognitive impairment. 72 patients with clinically significant agitation in the context of severe dementia were randomly assigned to the Melissa essential oil or placebo treatment group.

Researchers found that 60% of the Melissa oil group and 14% of the placebo-treated group experienced a 30% reduction of agitation scores. There was an overall improvement in agitation in 35% of patients receiving melissa oil and 11% in those treated with placebo, suggesting that quality of life was improved significantly with essential oil treatment.

A 2023 systematic review of randomized controlled trials "Natural remedies for Alzheimer's disease" published in Metab Brain Dis., by Saara Ahmad, Saad Bilal Ahmed, Asra Khan, Muhammad Wasim, Saiqa Tabassum, Saida Haider, Fatima Ahmed, Zehra Batool, Saima Khaliq, Hamna Rafiq, Prashant Tikmani, Anwar-Ul-Hassan Gilani, aimed to explore the role of natural alternatives in the treatment of Alzheimer's disease. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and Saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on Alzheimer's disease. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of Alzheimer's disease.

A 2020 randomized placebo-controlled double-blind 24-week trial "Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression" published in Science Rep. by Moeko Noguchi-Shinohara, Kenjiro Ono, Tsuyoshi Hamaguchi, Toshitada Nagai, Shoko Kobayashi, Junji Komatsu, Miharu Samuraki-Yokohama, Kazuo Iwasa, Kunihiko Yokoyama, Hiroyuki Nakamura, Masahito Yamada, using Melissa officinalis extract richly containing rosmarinic acid on patients with mild dementia due to Alzheimer's disease with the aim to examine the safety and tolerability (primary endpoint) of rosmarinic acid (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable Alzheimer's disease were randomized to either the placebo or Melissa officinalis extract group. No differences in vital signs or physical and neurologic examination results were detected between the Melissa officinalis and placebo groups. No serious adverse events occurred. There were no significant differences in cognitive measures; however, the mean Neuropsychiatric Inventory Questionnaire score improved by 0.5 points in the Melissa officinalis group and worsened by 0.7 points in the placebo group between the baseline and 24-week visit, indicating a significant difference (P = 0.012). No significant differences were apparent in disease-related biomarkers between the groups. Melissa officinalis extract containing 500 mg of rosmarinic acid taken daily was safe and well-tolerated by patients with mild dementia due to Alzheimer's disease. Our results suggest that rosmarinic acid may help prevent the worsening of Alzheimer's disease-related neuropsychiatric symptoms.

However, in 2011, a follow-up study seems to have refuted the evidence and shows that it had no more impact on the patients than medication or placebo. The researchers specifically point out that they blinded more factors in the study and used a more "rigorous design". The research is conflicting, but it seems Melissa oil does potentially do as well as medication can in some instances.

A 2022 study "Melissa officinalis L. ameliorates oxidative stress and inflammation and upregulates Nrf2/HO-1 signaling in the hippocampus of pilocarpine-induced rat" published in Environ Sci Pollut Res Int. by Hagar N Abd Allah, Manal Abdul-Hamid, Ayman M Mahmoud, Eman S Abdel-Reheim, evaluated the effect of Melissa officinalis extract (MOE) on oxidative stress, inflammation, and neurotransmitters in the hippocampus of pilocarpine - administered rats, pointing to the involvement of Nrf2/HO-1 signaling. Rats received neurotransmitters in the hippocampus of pilocarpine via intraperitoneal administration and were treated with Melissa officinalis extract for 2 weeks. Melissa officinalis extract prevented neuronal loss; decreased lipid peroxidation, Cox-2, PGE2, and BDNF; and downregulated glial fibrillary acidic protein in the hippocampus of neurotransmitters in the hippocampus of pilocarpine-treated rats. In addition, Melissa officinalis extract enhanced GSH and antioxidant enzymes, upregulated Nrf2 and HO-1 mRNA abundance, and increased the nuclear translocation of Nrf2 in the hippocampus of epileptic rats. Na⁺/K⁺-ATPase activity and GABA were increased, and glutamate and acetylcholine were decreased in the hippocampus of epileptic rats treated with Melissa officinalis extract. In conclusion, Melissa officinalis extract attenuated neuronal loss, oxidative stress, and inflammation; activated Nrf2/HO-1 signaling; and modulated neurotransmitters, GFAP, and Na⁺/K⁺-ATPase in the hippocampus of epileptic rats. These findings suggest that Melissa officinalis can mitigate epileptogenesis, pending further studies to explore the exact underlying mechanisms.

In a study Lemon Balm extract was given at a dose of 300 mg twice daily to a group of stressed people with mild-to-moderate anxiety and sleep disturbances. This study found that Lemon Balm reduced anxiety by 18%, reduced anxiety-associated symptoms by 15% and lowered insomnia by 42%.

According to a 2013 study published in Complementary Therapies in Clinical Practice, Lemon Balm improved insomnia in 85% of people with anxiety disorders and sleep disturbances in a pilot trial on 20 people. Oral Lemon Balm, alone or in combination with Valerian, improved sleep quality in a trial on 100 women suffering from menopause symptoms and insomnia and help relieve restlessness and sleep disorders such as insomnia. Similarly, a combination of Lemon Balm and Valerian improved sleep disturbances and restlessness in trials on over 900 children. Drink a cup of tea brewed with valerian and Lemon Balm before bed.

In a study from 2011, Lemon Balm was shown to help with mild-to moderate anxiety disorders and sleep disturbances. Another study found that menopausal women suffering from interrupted sleep reported much better rest after taking an extract of Lemon Balm and Valerian. In the study a Lemon Balm and Valerian combination was found to be as effective as the prescription drug Halcion.

Researchers in one 2006 study found that children who took a combined dose experienced a 70 to 80% improvement in symptoms. Both the researchers and parents regarded Lemon Balm as being a good or very good treatment. Still, more research is needed to validate these findings.

A 1999 clinical study from Inselspital in Bern, Switzerland, supports the idea that Lemon Balm's sedative action is potentiated in combination with other herbs with similar properties. However, to properly assess the benefits of Lemon Balm for sleep, it is also necessary to consider its traditional use in sleep disorders and its well-documented relaxing properties, which under appropriate conditions can lead to sleepiness.

A study explored the effects of Lemon Balm on sleep disturbances in people with chronic stable angina (CSA). The results demonstrated that 8-week supplementation with Lemon Balm can decrease depression, anxiety, stress, and sleep disorder in people who have CSA.

Other studies have found Lemon Balm to have positive effects on insomnia when combined with other herbs and nutrients. For example, IQP-AO-101 contains asparagus extract, saffron extract, Lemon Balm extract, vitamin C, vitamin E, and zinc. The clinical study results show that IQP-AO-101 improves sleep quality and well-being in people with moderate sleep disturbances and is well-tolerated.

A study from 2021 investigated the links between Lemon Balm and the benefits to postmenopausal women. The researchers concluded that they would recommend Lemon Balm to improve the quality of life of menopausal women with sleep disturbance.

In one trial using an orally administered extract of Lemon Balm leaf, subjects seemed to experience a significant drop in benign heart palpitation episodes, which is believed to be tied to its ability to enhance one’s mood.

Researchers gave an oral extract of the plant to animals in a 2016 study and found it resulted in a reduction of heart rate and blood pressure, plus they found indications of resistance to heart injury in lower doses.

The same 2012 study that discovered these results also revealed that inhaling Lemon Balm oil reduces some of the factors that lead to perpetual growth of a common liver cancer cell.

A 2022 study "Melissa officinalis L. Supplementation Provides Cardioprotection in a Rat Model of Experimental Autoimmune Myocarditis" published in Oxid Med Cell Longev by Nevena D Draginic, Vladimir L Jakovljevic, Jovana N Jeremic, Ivan M Srejovic, Marijana M Andjic, Marina R Rankovic, Jasmina Z Sretenovic, Vladimir I Zivkovic, Biljana T Ljujic, Slobodanka L Mitrovic, Stefani S Bolevich, Sergey B Bolevich, Isidora M Milosavljevic, due to existing evidence regarding antioxidant and anti-inflammatory effects of Melissa officinalis extracts, this study was aimed at investigating the potential of ethanolic Melissa officinalis extracts to prevent the development of myocarditis and its ability to ameliorate the severity of experimental autoimmune myocarditis (EAM) by investigating Melissa officinalis extracts effects on in vivo cardiac function, structure, morphology, and oxidative stress parameters. A total of 50 7-week-old male Dark Agouti rats were enrolled in the study and randomly allocated into the following groups: CTRL, nontreated healthy rats; experimental autoimmune myocarditis, nontreated rats with experimental autoimmune myocarditis; Melissa officinalis extracts 50, 100, and 200, rats with EAM treated with either 50, 100, or 200 mg/kg of Melissa officinalis extracts for 3 weeks per os. Myocarditis was induced by immunization of the rats with porcine myocardial myosin (0.5 mg) emulsion on day 0. Cardiac function and dimensions of the left ventricle (LV) were assessed via echocardiography. Additionally, the blood pressure and heart rate were measured. On day 21, rats were sacrificed and the hearts were isolated for further histopathological analyses (H/E and Picrosirius red staining). The blood samples were collected to determine oxidative stress parameters. The experimental autoimmune myocarditis group characteristically showed greater LV wall thickness and lower ejection fraction (50.33 ± 7.94% vs. 84.81 ± 7.74%) and fractional shortening compared to CTRL (p < 0.05). Melissa officinalis extracts significantly improved echocardiographic parameters (EF in Melissa officinalis extracts 200 81.44 ± 5.51%) and also reduced inflammatory infiltrate (by 88.46%; p < 0.001) and collagen content (by 76.39%; p < 0.001) in the heart tissues, especially in the MOE200 group compared to the experimental autoimmune myocarditis group. In addition, MOEs induced a significant decrease of prooxidants production (O₂ -, H₂O₂, and TBARS) and improved antioxidant defense system via increase in GSH, SOD, and CAT compared to experimental autoimmune myocarditis, with medium and high dose being more effective than low dose (p < 0.05). The present study suggests that ethanolic Melissa officinalis extracts, especially in a 200 mg/kg dose, improve cardiac function and myocardial architecture, possibly via oxidative stress mitigation, thus preventing heart remodeling, development of dilated cardiomyopathy, and subsequent heart failure connected with experimental autoimmune myocarditis. Melissa officinalis extracts might be considered as a potentially helpful adjuvant therapy in patients with autoimmune myocarditis.

A 2021 review "Melissa officinalis L. as a Nutritional Strategy for Cardioprotection" published in Front Physiol. by Nevena Draginic, Vladimir Jakovljevic, Marijana Andjic, Jovana Jeremic, Ivan Srejovic, Marina Rankovic, Marina Tomovic, Tamara Nikolic Turnic, Andrey Svistunov, Sergey Bolevich, Isidora Milosavljevic, aimed to provide a summary on the traditional uses, phytochemistry, and pharmacological activities in the cardiovascular system and cardiotoxicity of Melissa officinalis, with the special emphasis on the protective mechanisms in different cardiovascular pathologies. Active components are mainly located in the leaves or essential oil and include volatile compounds, terpenoid (monoterpenes, sesquiterpenes, triterpenes), and polyphenolic compounds (rosmarinic acid, caffeic acid, protocatechuic acid, quercitrin, rhamnocitrin, luteolin). For centuries, Melissa officinalis has been traditionally used as a remedy for memory, cognition, anxiety, depression, and heart palpitations. Up until now, several beneficial cardiovascular effects of Melissa officinalis, in the form of extracts (aqueous, alcoholic, and hydroalcoholic), essential oil, and isolated compounds, have been confirmed in preclinical animal studies, such as antiarrhythmogenic, negative chronotropic and dromotropic, hypotensive, vasorelaxant, and infarct size-reducing effects. Nonetheless, Melissa officinalis effects on heart palpitations are the only ones confirmed in human subjects. The main mechanisms proposed for the cardiovascular effects of this plant are antioxidant free radical-scavenging properties of Melissa officinalis polyphenols, amelioration of oxidative stress, anti-inflammatory effects, activation of M2 and antagonism of β1 receptors in the heart, blockage of voltage-dependent Ca²⁺ channels, stimulation of endothelial nitric oxide synthesis, prevention of fibrotic changes, etc. Additionally, the main active ingredient of Melissa officinalis-rosmarinic acid, per se, has shown substantial cardiovascular effects. Because of the vastness of encouraging data from animal studies, this plant, as well as the main ingredient rosmarinic acid, should be considered and investigated further as a tool for cardioprotection and adjuvant therapy in patients suffering from cardiovascular diseases.

A 2021 double-blind crossover randomized controlled clinical trial "Effect of Melissa officinalis on systolic and diastolic blood pressures in essential hypertension" published in Phytother Res. by Zahra Shekarriz, Seyed Afshin Shorofi, Maryam Nabati, Bizhan Shabankhani, Seyde Sedighe Yousefi aimed at evaluating the effects of Melissa officinalis on systolic and diastolic blood pressures in hypertensive patients. We conducted a double-blind, controlled, randomized crossover clinical trial on 49 patients who received either Melissa officinalis capsules (400 mg/d; n = 23) or the placebo (n = 26) three times per day for a 4-week period. After a 2-week washout period, the Melissa officinalis group received placebo and the other group received Melissa officinalis for another 4-week period. The systolic and diastolic blood pressures were measured once at baseline and then every 2 weeks for 10 weeks. The statistical analysis of the obtained data revealed that the chronology of the consumption of Melissa officinalis and placebo had no effect on the systolic and diastolic blood pressures in these two studied groups. Moreover, it was found that systolic and diastolic blood pressures significantly decreased after the consumption of M. officinalis, compared to placebo. Systolic and diastolic blood pressures in group A at the beginning of the study were 152.30 ± 5.312 mmHg and 95.52 ± 1.988 mmHg, respectively, and, after the first phase (drug use), reached 129.88 ± 9.009 mmHg and 80.13 ± 5.488 mmHg, respectively. Systolic and diastolic blood pressures in group B at the beginning of the study was 152.26 ± 5.640 mmHg and 94.44 ± 2.607 mmHg, respectively, and after the second phase (drug use), reached 131.77 ± 8.091 mmHg and 81.46 ± 7.426 mmHg, (p = .005), respectively. Also, no significant side effects were observed during the study. According to the results, Melissa officinalis can reduce systolic and diastolic blood pressures of the patients with essential hypertension.

An animal study, conducted in 2016, found that Melissa oil reduces the heart rate of injured rats and increases the heart’s resistance to injury.

Another 2015 animal study published in Research in Cardiovascular Medicine found that Melissa essential oil is associated with significant electrocardiogram alternations in rats. The electrocardiogram is a test that’s used to check for problems with the electrical activity of your heart.

A study, conducted in 2009, found that Melissa oil contains phenolic alkaloids that are among the properties that can inhibit cholesterol synthesis and lead to lower total cholesterol levels, total lipid levels and reduced lipid peroxidation levels in liver tissue.

A 2012 study published in The Journal of Nutrition suggests that ingesting Melissa oil could have beneficial metabolic effects. When used on mice, Melissa oil slowed fatty acid synthesis (a process that creates fatty buildups in the body), which reduced triglyceride levels.

A 2018 randomized controlled trial "The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina" published in Clin Nutr ESPEN by Habib Haybar, Ahmad Zare Javid, Mohammad Hosein Haghighizadeh, Einollah Valizadeh, Seyede Marjan Mohaghegh, Assieh Mohammadzadeh, 80 patients with CSA were divided randomly into two groups (taking 3 g Melissa officinalis supplement or placebo daily for 8 weeks). The shortened 21-item version of the depression, anxiety and stress scale test and Pittsburgh sleep quality index were done before and after the intervention. At the end of the study, the intervention group receiving Melissa officinalis capsules had a significant reduction in scores of depression, anxiety, stress, and total sleep disturbance, compared with the placebo group (P < 0.05). The results showed that 8-week supplementation with 3 g Melissa officinalis can decrease depression, anxiety, stress, and sleep disorder in patients with chronic stable angina.

In human and animal studies, taken for 14 days, an oral Lemon Balm extract reduced the frequency of heart beating in a trial of 55 people with palpitations. Lemon Balm protected against irregular heartbeats by inhibiting sodium and potassium ion channels, which slows down the heart rate. To sum up, research suggests that Lemon Balm may help with rapid heartbeats. However, the evidence is limited and further research is warranted.

A 2008 study showed that Melissa oil exhibited a higher degree of antibacterial activity than did Lavender oil against Gram-positive bacterial strains, including candida.

A 2023 study "Melissa officinalis essential oil as an antimicrobial agent against Listeria monocytogenes in watermelon juice" published in Food Microbiol., by Filomena Carvalho, Alexandra T Coimbra, Lúcia Silva, Ana P Duarte, Susana Ferreira, highlighted M. officinalis essential oil's antioxidant potential and antimicrobial activity against L. monocytogenes, presenting a bactericidal action and being able to inhibit some virulence attributes, such as biofilm formation. The pre-exposure of the bacterium to subinhibitory levels of essential oil (0.125 μL/mL) did not induce high tolerance to stresses (such as high temperature, low pH, osmotic stress and desiccation) or cross-resistance with antibiotics, while not modifying the invasion ability to Caco-2 cells. When applied in food model media (lettuce, chicken and milk) and watermelon juice, the essential oil showed to have antimicrobial activity in a lettuce leaf model medium, further diminishing L. monocytogenes contamination and inhibiting the natural microbiota present in watermelon juice. M. officinalis essential oil shows potential to be used as control of L. monocytogenes in watermelon juice, while increasing the food's microbial shelf life.

In a 2023 study "Anti-Candida and Antibiofilm Activity of Selected Lamiaceae Essential Oils" published in Front Biosci (Landmark Ed.), by Tomasz M Karpiński, Marcin Ożarowski, Agnieszka Seremak-Mrozikiewicz, Hubert Wolski, Essential oils of Lemon Balm (Melissa officinalis) and Oregano (Origanum vulgare) showed the best anti-Candida activity, with MIC values below 3.125 mg/mL. Lavender (Lavandula stoechas), Peppermint (Mentha × piperita), Rosemary (Rosmarinus officinalis), and Thyme (Thymus vulgaris) essential oils were also very active (0.39 to 6.25 or 12.5 mg/mL). Sage (Salvia officinalis) essential oil presented the lowest activity, with MIC values ranging from 3.125 to 100 mg/mL. In an antibiofilm study using MIC values, oregano and thyme essential oils showed the greatest effect, followed by lavender, mint, and rosemary oils. The weakest antibiofilm activity was observed with the lemon balm and sage oils. In silico toxicity research suggests that most of main compounds of Lamiaceae essential oils probably do not exhibit carcinogenicity, mutagenicity, or cytotoxicity. The obtained results showed that Lamiaceae essential oils have anti-Candida and antibiofilm activity. Further research is required to confirm the safety and efficacy of essential oils in the topical treatment of candidiasis.

A 2023 literature review "Antiviral Potential of Melissa officinalis L." published in Nutr Metab Insights, by Amirhossein Behzadi, Sadegh Imani, Niloofar Deravi, Zahra Mohammad Taheri, Fatemeh Mohammadian, Zahra Moraveji, Sepideh Shavysi, Motahareh Mostafaloo, Fateme Soleimani Hadidi, Sepehr Nanbakhsh, Sepehr Olangian-Tehrani, Mohammad Hesam Marabi, Parisa Behshood, Mohadeseh Poudineh, Ali Kheirandish, Kimia Keylani, Pooya Behfarnia, has shown that this plant can also fight viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV) through various mechanisms such as inhibiting HSV-1 from binding to host cell, inhibiting HSV-1 replication during the post-adsorption or inhibiting main protease and spike protein of SARS-CoV-2, furthermore, be effective in treating related diseases. This Review investigated the antiviral properties of Melissa officinalis and its effect on viral diseases. More in vitro and in vivo studies are needed to determine Melissa officinaliss underlying mechanism, and more randomized controlled trials should be done to identify its effect in humans. Also, due to the usefulness and lack of side effects, it can be used more as a complementary medicine.

In 1999, a clinical trial from The Cooperative Clinical Drug Research and Development GmbH, Germany, was carried out to evaluate the efficacy of applying Lemon Balm cream to herpes simplex cold sores. Lemon Balm's benefits as a topical treatment were validated in just two days. It showed a reduction in the healing period, preventing the spread of the infection and alleviating typical symptoms of herpes, such as itching, tingling, burning, swelling, tightness, and redness. Participants in this study applied either a Lemon Balm or placebo cream on the affected area four times per day for five days. The researchers also suggested that using Lemon Balm cream may help prolong the intervals between cold sore outbreaks. Further studies are needed to expand on these findings.

In another study in 1994 on 115 patients, a proprietary preparation of Lemon Balm extract in a lip balm showed efficacy in treating cold sores associated with the herpes simplex virus. Research has shown that the plant contains polyphenols, it can help significantly in the treatment of cold sores and combat the herpes simplex virus, shingles as well as other viral afflictions. Studies have shown a significant reduction in the duration and severity of herpes. Researchers also noted a "tremendous reduction" in the frequency of recurrence.

A German study comparing a cream containing Lemon Balm extract with a placebo found those who used the Lemon Balm cream had a significantly improved healing time. By day five, 50% more were symptom free than in the placebo group. To be effective, treatment must begin early. Researchers suggest that Melissa oil serves as a suitable topical treatment for getting rid of herpes because it has antiviral effects and is able to penetrate the skin due to its lipophilic nature.

A 2020 study "Glycerosome of Melissa officinalis L. Essential Oil for Effective Anti-HSV Type 1" published in Molecules by Giulia Vanti, Sotirios G Ntallis, Christos A Panagiotidis, Virginia Dourdouni, Christina Patsoura, Maria Camilla Bergonzi, Diamanto Lazari, Anna Rita Bilia, a commercial Melissa essential oil was analyzed by gas chromatography-mass spectrometry, loaded inside glycerosomes Melissa essential oil-GS and evaluated for its anti-herpetic activity against HSV type 1. Melissa essential oil-GS analyses were prepared by the thin layer evaporation method and they were characterized by light scattering techniques, determining average diameter, polydispersity index and ζ-potential. By transmission electron microscopy, Melissa essential oil-GS appeared as small nano-sized vesicles with a spherical shape. Melissa essential oil encapsulation efficiency inside glycerosomes, in terms of citral and β-caryophyllene, was found to be ca. 63% and 76% respectively, and Melissa essential oil release from glycerosomes, performed by dialysis bag method, resulted in less than 10% within 24h. In addition, Melissa essential oil-GS had high chemical and physical stability during 4 months of storage. Finally, Melissa essential oil-GS were very active in inhibiting HSV type 1 infection of mammalian cells in vitro, without producing cytotoxic effects. Thus, Melissa essential oil-GS could be a promising tool in order to provide a suitable anti-herpetic formulation.

According to a 2014 study published in Phytotherapy Research, Lemon Balm extract was able to prevent 80% to 96% of drug-resistant HSV-1 strains from infecting cells. The study found that the antiviral properties inhibited the spreading of herpes simplex virus type 1 into the healthy cells of the body. Lemon Balm extract in cream form is said to help in faster healing and the symptoms start decreasing when used repeatedly. Even Lemon Balm essential oil is effective in treating cold sores.

A 2012 study "Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro" published in Chemotherapy by Akram Astani, Jürgen Reichling, Paul Schnitzler, extracts and essential oils of medicinal plants are increasingly of interest as novel drugs for antiherpetic agents, since the herpes simplex virus might develop resistance to commonly used antiviral drugs. When drugs were added to HSV-1-infected cells, no antiviral effect was observed as determined by plaque reduction assay and analysis of expression of viral protein ICP0. However, the Melissa extract demonstrated a high virucidal activity against HSV-1, even at very low concentrations of 1.5 μg/ml, whereas similar results for phenolic compounds were only achieved at 100 times higher concentrations. Besides the virucidal activity, the Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner. These results indicate that rosmarinic acid was the main contributor to the antiviral activity of Melissa extract. However, the selectivity index of Melissa extract of 875 against HSV is superior to the selectivity indices of single constituents. Melissa extract exhibits low toxicity, is virucidal and affects HSV-1 attachment to host cells in vitro.

Another 2008 study "Melissa officinalis oil affects infectivity of enveloped herpesviruses" published in Phytomedicine by P Schnitzler, A Schuhmacher, A Astani, Jürgen Reichling, The inhibitory activity against herpes simplex virus type 1 and herpes simplex virus type 2 was tested in vitro on monkey kidney cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of balm oil for herpes simplex virus plaque formation was determined at high dilutions of 0.0004% and 0.00008% for HSV-1 and HSV-2, respectively. At noncytotoxic concentrations of the oil,plaque formation was significantly reduced by 98.8% for HSV-1 and 97.2% for HSV-2, higher concentrations of Lemon Balm oil abolished viral infectivity nearly completely. In order to determine the mode of antiviral action of this essential oil, time-on-addition assays were performed. Both herpesviruses were significantly inhibited by pretreatment with balm oil prior to infection of cells. These results indicate that Melissa oil affected the virus before adsorption, but not after penetration into the host cell, thus Lemon Balm oil is capable of exerting a direct antiviral effect on herpesviruses. Considering the lipophilic nature of Lemon Balm essential oil, which enables it to penetrate the skin, and a high selectivity index, Melissa officinalis oil might be suitable for topical treatment of herpetic infections.

A 2006 review "Natural remedies for Herpes simplex" published in Alternative Medicine Review by Alan R Gaby, gived evidence that certain dietary modifications and natural substances may be useful for treating active Herpes simplex lesions or preventing recurrences. Treatments discussed include lysine, vitamin C, zinc, vitamin E, adenosine monophosphate, and Lemon Balm (Melissa officinalis).

A 2021 study "Identification of Main Protease of Coronavirus SARS-CoV-2 (M^pro) Inhibitors from Melissa officinalis" published in Curr Drug Discov Technol. by Olusola O Elekofehinti, Opeyemi Iwaloye, Courage D Famusiwa, Olanrewaju Akinseye, Joao B T Rocha, compounds previously characterized by Melissa officinalis were queried against the main protease of coronavirus SARS-CoV-2 using a computational approach. Melitric acid A and salvanolic acid A had higher affinity than lopinavir and ivermectin using both AutodockVina and XP docking algorithms. The computational approach was employed in the generation of the QSAR model using automated QSAR, and in the docking of ligands from Melissa officinalis with SARS-CoV-2 Mpro inhibitors. The best model obtained was KPLS_Radial_ 28 (R² = 0.8548 and Q²=0.6474, which was used in predicting the bioactivity of the lead compounds. Molecular mechanics based MM-GBSA confirmed salvanolic acid A as the compound with the highest free energy and predicted bioactivity of 4.777, it interacted with His-41 of the catalytic dyad (Cys145-His41) of SARS-CoV-2 main protease (M^pro), as this may hinder the cutting of inactive viral protein into active ones capable of replication. Salvanolic acid A can be further evaluated as a potential M^pro inhibitor.

A small study from 2010 assessed the effects of a cold dessert containing Lemon Balm on functional dyspepsia. The study looked at 30 people with functional dyspepsia, a condition that can cause an upset stomach. Participants ate a sorbet, with or without the herb, after a meal. they had also combined with another herb (Artichoke, or Cynara scolymus). Although both types of desserts lessened the symptoms and their intensity, the dessert containing Lemon Balm intensified this effect. Participants who ate the dessert with the herbs experienced less stomach upset than those who did not. More research is needed.

A 2019 study on rats demonstrated that Lemon Balm decreased the intestinal transit time, the time it takes food to travel from the mouth through the gastrointestinal tract. Further research is needed to conclude how effective Lemon Balm is for the GI.

A 2005 review assessing the results of several studies on Lemon Balm found the herb to be useful in treating gastrointestinal symptoms such as this. Although this is a promising development, it’s important to recognize the study limitations.

Lemon Balm significantly decreased average daily crying time after 28 days in 200 colicky infants and reduced colic episodes through its calming effects and by relaxing the gut. A single clinical trial cannot be considered sufficient evidence to claim that Lemon Balm improves infant colic. Additional clinical trials are needed to confirm the results of this study.

According to a multi-center study, Lemon Balm with valerian may help treat sleeping problems and restlessness in children. The study included over 918 children younger than 12 years old who experienced restlessness and dyssomnia (a collection of sleep disorders). They received a combined valerian and Lemon Balm preparation. It was conducted and found that more than 80% saw improvements in their problems sleeping when taking the supplements. In addition, 70% of the children saw improvements in restlessness. Finally, none of the children experienced adverse effects from the medication.

A study in 2017 showed that consuming Lemon Balm extract may help reduce moderate to severe dysmenorrhea. The researchers noted that this effect may be related to the antispasmodic effects of this herb.

A 2015 Iranian study published in Nursing and Midwifery Studies, assessed the effect of Melissa essential oil capsules on the intensity of PMS symptoms. A 100 high school girls participated in a double-blind, randomized, placebo-controlled trial. The intervention group participants received a capsule with 1,200 milligrams of Melissa oil from the first to the last day of their menstrual cycles for three consecutive cycles. The second group received the placebo. The results revealed a significant reduction in PMS symptoms for the intervention group, suggesting that Melissa oil is effective in reducing PMS symptoms. The intensity of PMS symptoms was analyzed before and one, two, and three months after the trial. The group who took the Lemon Balm reported a significant reduction in symptoms. Further research is needed to confirm these findings.

A 2021 randomized double-blind clinical trial "The Effectiveness of Melissa Officinalis L. versus Citalopram on Quality of Life of Menopausal Women with Sleep Disorder" published in Rev Bras Ginecol Obstet by Mahboobeh Shirazi, Mohamad Naser Jalalian, Masoumeh Abed, Marjan Ghaemi, aimed to assess the effect of Melissa Officinalis L. (a combination of Lemon Balm with Fennel fruit extract) compared with citalopram and placebo on the quality of life of postmenopausal women with sleep disturbance. The present study is a randomized, double-blind, placebo clinical trial among 60 postmenopausal women with sleep disturbance who were referred to a university hospital from 2017 to 2019. The participants were randomized to receive Melissa Officinalis (500 mg daily), citalopram (30 mg) or placebo once daily for 8 weeks. The Menopause-Specific Quality of Life questionnaire was self-completed by each participant at baseline and after 8 weeks of the intervention and was compared between groups. The mean for all MENQOL domain scores were significantly improved in the Melissa Officinalis group compared with citalopram and placebo (p < 0.001). The mean ± standard deviation after 8 weeks in the Melissa Officinalis, citalopram and placebo groups was 2.2 ± 0.84 versus 0.56 ± 0.58 versus 0.36 ± 0.55 in the vasomotor (p < 0.001), 1.02 ± 0.6 versus 0.28 ± 0.2 versus 0.17 ± 0.1 in the psychomotor-social (p < 0.001), 0.76 ± 0.4 versus 0.25 ± 0.1 versus 0.11 ± 0.1 in the physical and 2.3 ± 1.0 versus 0.35 ± 0.5 versus 0.41 ± 0.5 in the sexual domain, respectively. The results revealed that Melissa Officinalis may be recommended for improving the quality of life of menopausal women with sleep disturbance.

"A review of effective herbal medicines in controlling menopausal symptoms" published in Electron Physician, 2017 by Rahele Kargozar, Hoda Azizi, Roshanak Salari, Rahele Kargozar 1, Hoda Azizi 2, Roshanak Salari, showed that the medicinal plants, which include Sage herb (Salvia officinalis), Lemon Balm (Melissa officinalis), Valerina officinalis, Black cohosh (Cimicifuga racemosa), Fenugreek (Trigonella foenum-graecum), Black cumin (Nigella sativa), Vitex (Vitex agnus-castus), Fennel (Foeniculum vulgare), Evening primrose (Oenothera biennis), Ginkgo biloba, Alfalfa (Medicago sativa), Hypericum perforatum, Panax ginseng, Pimpinella anisum, Licorice (Glycyrrhiza glabra), Passiflora incarnata, Red clover (Trifolium pratense), and Glycine soja were effective in the treatment of acute menopausal syndrome with different mechanisms. Medicinal plants can play an imperative role in the treatment of acute menopausal syndrome, however, further studies are required to buttress their efficacy in the treatment of acute menopausal syndrome.

A study shows that Lemon Balm reduced swelling caused by injury and inflammation in mice. Lemon Balm also reduced the levels of the inflammatory proteins TNF-alpha, IL-1, and IL-6.

A 2022 comparative study "Anti-inflammatory and Antioxidant Effects of Melissa officinalis Extracts" published in Iran Journal Pharm Res., by Nevena Draginic, Marijana Andjic, Jovana Jeremic, Vladimir Zivkovic, Aleksandar Kocovic, Marina Tomovic, Biljana Bozin, Nebojsa Kladar, Sergey Bolevich, Vladimir Jakovljevic, Isidora Milosavljevic, aimed to evaluate and compare the content of active components, antioxidant, and anti-inflammatory potential of three different Melissa officinalis extracts (Melissa officinalis Essential oils), ethanolic macerate (E₁), aqueous (E₂), and ethanolic (E₃), obtained under reflux and their effects on systemic redox status after acute per os administration in vivo post-carrageenan application. The HPLC analysis revealed that the most abundant constituent in all the three extracts was rosmarinic acid (RA), with higher content in E₁ and E₃ than in E₂ (P < 0.05). The highest flavonoid content was found in the aqueous extract, especially quercetin (P < 0.05). For the carrageenan-induced paw edema model, dark agouti rats were used and divided into the groups: Control, indomethacin, E₁, E₂, and E₃ subgrouped according to applied doses: 50, 100, and 200 mg/kg. Ethanolic macerate (E₁200) and aqueous (E₂100) Melissa officinalis extract were shown to be anti-inflammatory agents in the carrageenan paw edema model, with the most prominent edema inhibition in the sixth hour post-carrageenan (63.89% and 69.44%, respectively, vs. 76.67% in the indomethacin group). All the three extracts reduced the production of pro-oxidants H₂O₂ and TBARS post-carrageenan and increased GSH levels compared to control (P < 0.05). These data imply the possible future usage of Melissa officinalis Essential oils to prevent inflammatory and oxidative stress-related diseases.

A 2013 study published in Advances in Pharmacological Science, investigated the anti-inflammatory properties of Melissa essential oil by using experimental trauma-induced hind paw edema in rats. The anti-inflammatory properties of oral administration of Melissa oil showed a significant reduction and inhibition of edema, which is swelling caused by excess fluid that is trapped in the body’s tissues. The results of this study and many like it suggest that Melissa oil can be taken internally or applied topically to reduce swelling and relieve pain due to its anti-inflammatory activity.

Test tube studies have found that Lemon Balm blocks the attachment of antibodies to the thyroid cells that cause Grave's disease. The brain's signal to the thyroid (thyroid-stimulating hormone or TSH) is also blocked from further stimulating the excessively active thyroid gland in this disease.

According to research conducted in the laboratory, dry extract of Lemon Balm balances the thyroid hormone. In addition, it also prevents thyroid hormones from becoming over-stimulated.

Although laboratory and animal studies show that Lemon Balm may help decrease thyroid in the body, no human studies have yet been conducted for this possible use.

A study in 2021 discussed how two individuals with Graves’ disease consumed bugleweed and Lemon Balm. Over time, both individuals had normal blood levels of thyroid-stimulating hormone. However, further study of the anti-thyroidal effects of Lemon Balm in humans is required to evaluate it as a therapy in Graves’ disease.

A 2022 study "Light emitting diodes improved the metabolism of rosmarinic acid and amino acids at the transcriptional level in two genotypes of Melissa officinalis L" published in Funct Plant Biol., by Tayebeh Ahmadi, Leila Shabani, Mohammad R Sabzalian, used different LEDs to evaluate their effect on metabolic and transcriptional reprogramming of two genotypes (Ilam and Isfahan) of lemon balm grown under narrow-band LED lighting. Lemon balm plants were grown in four incubators equipped with artificial lighting and subjected to four LED lamps [White, Blue, Red, and mixed RB (Red+Blue) (70%:30%)] and in greenhouse conditions for 7weeks. The results showed significant increases in leaf number, pigment and soluble sugar contents, secondary metabolites, and calcium, magnesium, potassium and amino acid contents achieved in growth under mixed RB LEDs. As observed for the content of total phenolics, rosmarinic acid, and amino acids, the expression of genes involved in their production, including TAT , RAS , and DAHPS were also enhanced due to the mixed RB LED lighting. The best condition for both the plant growth and expression of genes was under the mixture of Red+Blue LED lamps. These observations indicate that the increase in secondary metabolites under mixed Red+Blue lights may be due to the increase in primary metabolites synthesis and the increased expression of genes that play an essential role in the production of secondary metabolites.

A 2008 study "Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice" published in Journal of Ethnopharmacology, Vol 115, Issue 2, by Jinmi Lee, Kyungsil Chae et al., about mixture of three herbs, Morus alba, Melissa officinalis and Artemisia iwayomogi was shown to regulate body weight, adipose tissue mass, lipid metabolism, in part, through changes in the expression of hepatic PPAR-alpha target genes.

"A Comprehensive Review of Herbal Supplements Used for Persistent Symptoms Attributed to Lyme Disease" published in Integr Med (Encinitas) 2023, by Allison Thompson, Lauren M Hynicka, Kalpana D Shere-Wolfe in University of Maryland Medical Center, Baltimore MD, examines the evidence for the antimicrobial activity, safety, and drug-drug interactions of 18 herbal supplements that patients commonly use for treatment of persistent symptoms attributed to Lyme disease. The research team performed a narrative review by searching the PubMed, Embase, Scopus, Natural Medicines databases, and NCCIH website. The search used the keywords for 18 herbal compounds: Andrographis (Andrographis paniculate), Astragalus (Astragalus propinquus), Berberine, Cat's Claw bark (Uncaria tomentosa), Cordyceps (Cordyceps sinensis), Cryptolepis (Cryptolepis sanguinolenta), Chinese Skullcap (Scutellaria baicalensis), Garlic (Allium sativum), Japanese Knotwood (Polygonum cuspidatum), Reishi Mushrooms (Ganoderma lucidum), Sarsaparilla (Smilax medica), Siberian Ginseng (Eleutherococcus senticosus), Sweet Wormwood (Artemisia annua), Teasle root (Dipsacus fullonum), Lemon Balm (Melissa officinalis), oil of Oregano (Origanum vulgare), Peppermint (Mentha x piperita), and Thyme (Thymus vulgaris). The team also searched for terms related to protocols, including Dr. Rawls' protocol and the Buhner protocol. Seven of the 18 herbs reviewed had evidence for in-vitro activity against Borrelia burgdorferi. These compounds included: Cat's Claw, Cryptolepis, Chinese Skullcap, Japanese Knotweed, Sweet Wormwood, Thyme, and oil of Oregano. With the exception of oil of Oregano these compounds also have anti-inflammatory activity. In vivo data and clinical trials are lacking. Clinicians should be cautious as many of the identified compounds have drug interactions and additive effects that could lead to increased risks for bleeding, hypotension, and hypoglycemia. Many of the herbs that alternative and integrative practitioners use to treat Lyme disease have anti-inflammatory effects that may contribute to patients' perceptions of symptomatic improvement. Some herbs have limited demonstrated anti-borrelial activity in vitro, but in-vivo data and clinical trial data is lacking. Further research is required to determine the efficacy, safety and appropriate use of these herbs for this patient population.

In a clinical trial on 62 people with type 2 diabetes, an oral Lemon Balm supplement improved blood sugar control (by increasing insulin sensitivity). It also increased the levels of cholesterol bound to HDL, suggesting it helped prevent artery clogging.

In another trial on 70 diabetics, the same supplement was safe and improved the levels of fats and proteins that transport them in the blood, possibly reducing the risk of heart disease. Lemon Balm helped with type 2 diabetes by lowering blood sugar and fat levels in mice.

Researchers at The Free University of Berlin impressed by the convincing data from their studies stated, "Ethanolic Lemon Balm extract can potentially be used to prevent or concomitantly treat type 2 diabetes". Taking Lemon Balm along with diabetes medications might cause your blood sugar to go too low. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed. Results of this preclinical trial in type 2 diabetes showed a significant reduction in blood glucose, as well as an improved glucose tolerance and significantly higher serum insulin levels. In spite of the extensive scientific research, there's much about Lemon Balm health benefits that remains unknown. However, the extended popularity of this herb through history is a reliable testimony of its anxiolytic, sedative, and antiviral benefits. Recent findings suggest that this herb has an amazing, untapped potential, and more benefits of Lemon Balm are yet to be corroborated by further research.

A 2010 study published in The British Journal of Nutrition found that when mice were administered Melissa essential oil for 6 weeks, they showed significantly reduced blood glucose levels, improved glucose tolerance and significantly higher serum insulin levels compared with the control group, all of which can reduce diabetes symptoms.

A 2023 phase 2a, randomized, double-blind, placebo-controlled study "Assess the Efficacy and Safety of ALS-L1023 in Non-Alcoholic Fatty Liver Disease" published in Pharmaceuticals (Basel), by Gi-Ae Kim, Hyun Chin Cho, Soung Won Jeong, Bo-Kyeong Kang, Mimi Kim, Seungwon Jung, Jungwook Hwang, Eileen L Yoon, Dae Won Jun, shown that the herbal extract, ALS-L1023, from Melissa officinalis reduces visceral fat and hepatic steatosis. We aimed to assess the safety and efficacy of ALS-L1023 as the treatment of non-alcoholic fatty liver disease (NAFLD). We conducted a 24-week randomized, double-blind, placebo-controlled 2a study in patients with NAFLD (MRI-proton density fat fraction [MRI-PDFF] ≥ 8% and liver fibrosis ≥ 2.5 kPa on MR elastography [MRE]) in Korea. Patients were randomly assigned to 1800 mg ALS-L1023 (n = 19), 1200 mg ALS-L1023 (n = 21), or placebo (n = 17) groups. Efficacy endpoints included changes in liver fat on MRI-PDFF, liver stiffness on MRE, and liver enzymes. For the full analysis set, a relative hepatic fat reduction from baseline was significant in the 1800 mg ALS-L1023 group (-15.0%, p = 0.03). There was a significant reduction in liver stiffness from baseline in the 1200 mg ALS-L1023 group (-10.7%, p = 0.03). Serum alanine aminotransferase decreased by -12.4% in the 1800 mg ALS-L1023 group, -29.8% in the 1200 mg ALS-L1023 group, and -4.9% in the placebo group. ALS-L1023 was well tolerated and there were no differences in the incidence of adverse events among the study groups. ALS-L1023 could reduce hepatic fat content in patients with NAFLD.

In a 2023 study "Melissa Officinalis L. aqueous extract pretreatment decreases methotrexate-induced hepatotoxicity at lower dose and increases ^99mTc-phytate liver uptake, as a probe of liver toxicity assessment, in rats" published in Ann Nucl Med., by Somayeh Shahani, Nasrin Mehraban, Fereshteh Talebpour Amiri, Seyed Mohammad Abedi, Zohreh Noaparast, Salam Mohammadinia, adult female Wistar rats were received or not M. officinalis aqueous extract at doses of 100 mg/kg (for 14 and 24 consecutive days) and 2 g/kg (for 14 consecutive days) by gavage technique. MTX (20 mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M. officinalis treatment. 24 h after the last day of treatment, 99mTc-phytate was intravenously injected through the tail of rats. Animals were killed at 20 min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99mTc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy. A significant increase in liver radioactivity was detected in M. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100 mg/kg for 14 days. Also, a significant reduction in liver radioactivity was evident with M. officinalis extract at a dose of 2 g/kg for 14 days in comparison with the control group, this reduction was not significant at the lower dose of 100 mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect of M. officinalis vs MTX-induced liver injury in rats. In conclusion, we highlighted the liver uptake of ^99mTc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100 mg/kg for 14 days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses.

In a 2022 study "ALS-L1023 from Melissa officinalis Alleviates Liver Fibrosis in a Non-Alcoholic Fatty Liver Disease Model"  published in Life (Basel), by Eun Jeoung Lee, Yun Kim, Ji Eun Kim, Eileen Laurel Yoon, Sung Ryol Lee, Dae Won Jun, ALS-L1023 is an ingredient extracted from Melissa officinalis L. (Labiatae; lemon balm), which is known as a natural medicine that suppresses angiogenesis. Herein, we aimed to determine whether ALS-L1023 could alleviate liver fibrosis in the non-alcoholic fatty liver disease (NAFLD) model. C57BL/6 wild-type male mice (age, 6 weeks old) were fed a choline-deficient high-fat diet (CDHFD) for 10 weeks to induce NAFLD. For the next 10 weeks, two groups of mice received the test drug along with CDHFD. Two doses (a low dose, 800 mg/kg/day; and a high dose, 1200 mg/kg/day) of ALS-L1023 were selected and mixed with feed for administration. Obeticholic acid (OCA; 10 mg/kg/day) was used as the positive control. Biochemical analysis revealed that the ALS-L1023 low-dose group had significantly decreased alanine transaminase and aspartate transaminase. The area of fibrosis significantly decreased due to the administration of ALS-L1023, and the anti-fibrotic effect of ALS-L1023 was greater than that of OCA. RNA sequencing revealed that the responder group had lower expression of genes related to the hedgehog-signaling pathway than the non-responder group. ALS-L1023 may exert anti-fibrotic effects in the NAFLD model, suggesting that it may provide potential benefits for the treatment of liver fibrosis.

In a review of studies, researchers found that Lemon Balm, in sufficient concentrations, helped to relax smooth muscle tissue in an animal model. However, they found that a concentration of 30% was not enough to exhibit smooth muscle relaxation.

A 2014 study published in Cancer Investigation, found that Melissa oil may be of potential interest for the treatment of glioblastoma multiforme (GBM), which are tumors that arise from the supportive tissue of the brain. The study investigated the activity of Melissa essential oil and its major component citral in GBM cell lines. Both Melissa oil and citral decreased the viability and induced apoptosis of GBM cells with their antioxidant effects, showcasing its potential as a natural cancer treatment.

Another 2004 study found that Melissa essential oil has potential as an anti-tumor agent, as evidenced by a reduction of human cancer cell lines when evaluated in an in vitro study.

A 2022 study "Quantitative Proteome Analysis Reveals Melissa officinalis Extract Targets Mitochondrial Respiration in Colon Cancer Cells" published in Molecules, by Tzu-Ting Kuo, Li-Chun Lin, Hsin-Yi Chang, Pei-Jung Chiang, Hsin-Yi Wu, Tai-Yuan Chen, Shih-Min Hsia, Tsui-Chin Huang, showed that hot water Melissa officinalis extract exhibited anticancer activity in colorectal cancer. However, the detailed mechanisms underlying Melissa officinalis-induced cell death remain elusive. To elucidate the anticancer regulation of Melissa officinalis extract in colon cancer, a data-driven analysis by proteomics approaches and bioinformatics analysis was applied. An isobaric tandem mass tags-based quantitative proteome analysis using liquid chromatography-coupled tandem mass spectrometry was performed to acquire proteome-wide expression data. The over-representation analysis and functional class scoring method were implemented to interpret the Melissa officinalis-induced biological regulations. In total, 3465 quantifiable proteoforms were identified from 24,348 peptides, with 67 upregulated and 54 downregulated proteins in the Melissa officinalis-treated group. Mechanistically, Melissa officinalis impeded mitochondrial respiratory electron transport by triggering a reactive oxygen species (ROS)-mediated oxidative stress response. Melissa officinalis hindered the mitochondrial membrane potential by reducing the protein expression in the electron transport chain, specifically the complex I and II, which could be restored by ROS scavenger. The findings comprehensively elucidate how Melissa officinalis hot water extract activates antitumor effects in colorectal cancer colorectal cancer cells.

A 2020 study "Melissa officinalis Extract Induces Apoptosis and Inhibits Migration in Human Colorectal Cancer Cells" published in ACS Omega by Tzu-Ting Kuo, Hsin-Yi Chang, Tai-Yuan Chen, Bai-Chia Liu, Hsin-Yi Chen, Yuan-Chin Hsiung, Shih-Min Hsia, Chun-Ju Chang, Tsui-Chin Huang, examine the antitumor effects of nine components frequently found in herbal tea and uncover the underlying molecular mechanism. Among them, the hot water extract of Melissa officinalis exhibited the highest anticancer activity on colorectal cancer cells. We revealed that Melissa officinalis reduced cell proliferation, induced cell cycle arrest at the G2/M phase, triggered caspase-dependent apoptotic cell death, and inhibited cell migration ability by modulating the epithelial-mesenchymal transition in HCT116 colorectal cancer cells. To examine the metabolite composition in the Melissa officinalis hot water extract, we applied mass spectrometry-based analysis and identified 67 compounds. Among them, the phenolic compounds, including lignans, phenylpropanoids, and polyketides, are widely found in natural products and possess various bioactivities such as anti-inflammatory, antioxidation, and anticancer effects. The results indicate that herbal tea consumption benefits colorectal cancer prevention and management.

In cell-based studies, Lemon Balm killed breast cancer cells and blocked their multiplication. It probably did so by decreasing antigen KI-67 (a protein that is associated with cell growth and reproduction).

In a 2023 study "Green synthesis of silver nanoparticles, graphene, and silver-graphene nanocomposite using Melissa officinalis ethanolic extract: Anticancer effect on MCF-7 cell line" published in Iran Journal Basic Med Sci., by Farzaneh Motafeghi, Mahyar Gerami, Parham Mortazavi, Babak Khayambashi, Nasrin Ghassemi-Barghi, Mohammad Shokrzadeh, the rate of inhibition of cancer cell growth and production of reactive oxygen radicals, malondialdehyde, and glutathione stores in MCF7 cells were investigated. Cancer cells were exposed to nano particles for 48 hr. Silver nanoparticles and graphene both reduced the growth rate of MCF-7. Subsequently, by treating the cells with silver-graphene nanocomposite, the rate of inhibition of cell growth at the highest concentration was 84.60%. Nanoparticles also inhibited the growth of cancer cells through the oxidative stress pathway by increasing the amount of intracellular ROS, followed by increasing malondialdehyde and decreasing glutathione stores, so that at the highest combined concentration of nanoparticles, the amounts of LPO and ROS increased up to 70% and 74 %, and glutathione reserves decreased by 16%. Treatment of MCF-7 cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors, such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation. According to the mathematical model, silver graphene nanocomposite> silver nanoparticles> graphene has the best effect in inhibiting the growth of cancer cells, respectively.

In a cell-based study, Lemon Balm killed brain cancer cells. Citral in Lemon Balm may activate cancer cell self-destruction (through caspase-3) and increases cancer’s sensitivity to chemotherapy by inhibiting the drug-resistant gene MRP1.

A 2023 study "The Bright and Dark Sides of Herbal Infusions: Assessment of Antioxidant Capacity and Determination of Tropane Alkaloids" published in Toxins (Basel), by Ana Rita Soares Mateus, Carmen Crisafulli, Matilde Vilhena, Sílvia Cruz Barros, Angelina Pena, Ana Sanches Silva, presents an optimized and validated methodology based on the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction procedure followed by Ultra-High Performance Liquid Chromatography combined with Time-of-Flight Mass Spectrometry (UHPLC-ToF-MS) for the determination of tropane alkaloids (atropine, scopolamine, anisodamine, and homatropine) in herbal infusions, in accordance with criteria established by Commission Recommendation EU No. 2015/976. One of the seventeen samples was contaminated with atropine, exceeding the current European regulation regarding tropane alkaloids. In addition, this study evaluated the antioxidant capacity of common herbal infusions available on Portuguese markets, indicating the high antioxidant capacity of Yerba Mate (Ilex paraguariensis), Lemon Balm (Melissa officinalis), and Peppermint (Mentha x piperita).

A 2023 study "Development of Dairy Products Fortified with Plant Extracts: Antioxidant and Phenolic Content Characterization" published in Antioxidants (Basel) by Aikaterini Kandyliari, Panagiota Potsaki, Panoraia Bousdouni, Chrysoula Kaloteraki, Martha Christofilea, Kalliopi Almpounioti, Andreani Moutsou, Chistodoulos K Fasoulis, Leandros V Polychronis, Vasileios K Gkalpinos, Andreas G Tzakos, Antonios E Koutelidakis, focused on the analysis of dairy products, including kefir, cream cheese, yogurt, and vegan yogurt, enhanced with aqueous extracts of plant byproducts (Citrus aurantium peel, Citrus limon peel and Rosa canina seed) and herbs (Sideritis spp., Hypericum perforatum, Origanum dictamnus, Mentha pulegium L., Melissa oficinallis, Mentha spicata L. and Lavandula angustifolia) to characterize their antioxidant content, phenolic profile, and organoleptic characteristics. Antioxidant and phenolic content were determined by Folin-Ciocalteu and ferric reducing antioxidant power (FRAP) assays and presented values up to 46.61 ± 7.22 mmol Fe²⁺/L and 82.97 ± 4.29 mg gallic acid (GAE)/g, respectively for the aqueous extracts, as well as up to 0.68 ± 0.06 mmol Fe²⁺/L and 2.82 ± 0.36 mg GAE/g for the fortified dairy products. The bioavailability of antioxidants and phenolics in fortified foods was determined after in vitro digestion and ranged between 4 and 68%. The phytochemical profile of the aqueous extracts was determined by mass spectrometry, and 162 phytochemicals were determined, from which 128 belong to the polyphenol family including flavonoids and phenolic acids. Furthermore, most of the identified compounds have been recorded to possess enhanced antioxidant capacity in correlation to the in vitro findings. Finally, organoleptic evaluation showed an overall acceptability around 3.0 ± 1.0 on a 5-point scale. In conclusion, the studied plants and herbal extracts can be used for the fortification of a variety of dairy products with potential positive effects on human health.

In another 2023 study "Electrospun PLA-Based Biomaterials Loaded with Melissa officinalis Extract with Strong Antioxidant Activity" published in Polymers (Basel), by Nikoleta Stoyanova, Mariya Spasova, Nevena Manolova, Iliya Rashkov, Mariana Kamenova-Nacheva, Plamena Staleva, Maya Tavlinova-Kirilova, the plant extract Melissa officinalis (M. officinalis) was successfully loaded in polymer fibrous materials on the basis of a biodegradable polyester-poly(L-lactide) (PLA) and biocompatible polyether-polyethylene glycol (PEG) by applying the electrospinning method. The optimal process conditions for the preparation of hybrid fibrous materials were found. The extract concentration was varied-0, 5 or 10 wt% in respect of the polymer weight, in order to study its influence on the morphology and the physico-chemical properties of the obtained electrospun materials. All the prepared fibrous mats were composed of defect-free fibers. The mean fiber diameters of the PLA, PLA/M. officinalis (5 wt%) and PLA/M. officinalis (10 wt%) were 1370 ± 220 nm, 1398 ± 233 nm and 1506 ± 242 nm, respectively. The incorporation of the M. officinalis into the fibers resulted in slight increase of the fiber diameters and in increase of the water contact angle values to 133°. The presence of the polyether in the fabricated fibrous material assisted the wetting of the materials imparting them with hydrophilicity (the value of the water contact angle become 0°). Extract-containing fibrous materials displayed strong antioxidant activity as determined by the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method. The DPPH solution color changed to yellow and the absorbance of the DPPH radical dropped by 88.7% and 91% after being in contact with PLA/M. officinalis and PLA/PEG/M. officinalis mats, respectively. These features revealed the M. officinalis-containing fibrous biomaterials promising candidates for pharmaceutical, cosmetic and biomedical use.

A 2020 study "Does Melissa officinalis consumption improve the salivary antioxidant status of smokers?" published in Caspian J Intern Med by Sedigheh Bakhtiari, Zahra Yadegari, Puriya Ehyaei, Narges Gholizadeh, was to investigate the effects of Melissa officinalis tea on the total antioxidant capacity of saliva among smokers. 24 smokers were selected by convenience sampling. Demographic information and duration of smoking were recorded at the beginning of study. Two cups of Melissa officinalis tea were given to the participants with specific instruction for 30 days. The unstimulated saliva was collected on first day, 15th and 30th days. Then, total antioxidant capacity was measured by a special kit. Statistical analysis was conducted by repeated measure ANOVA test. The mean values of total antioxidant capacity of saliva were significantly higher in days 15 and 30 from the baseline. (p<0.0001, P=0.006). In day 30, the mean value of antioxidant was not significantly different from day 15. (P=0.271). Melissa officinalis tea consumption increases salivary antioxidants level in smokers.

A 2022 study "Short-Term Administration of Lemon Balm Extract Ameliorates Myocardial Ischemia/Reperfusion Injury: Focus on Oxidative Stress" published in Pharmaceuticals (Basel), by Nevena Draginic, Isidora Milosavljevic, Marijana Andjic, Jovana Jeremic, Marina Nikolic, Jasmina Sretenovic, Aleksandar Kocovic, Ivan Srejovic, Vladimir Zivkovic, Sergey Bolevich, Stefani Bolevich, Svetlana Curcic, Vladimir Jakovljevic, aimed to investigate the cardioprotective effects of ethanolic Melissa officinalis L. extract in the rat model of myocardial ischemia/reperfusion (I/R) injury. Thirty-two Wistar rats were randomly divided into a CTRL non-treated control group with myocardial I/R injury and three experimental groups of rats treated with 50, 100, or 200 mg/kg of ME for 7 days per os. Afterward, hearts were isolated, and cardiodynamic function was assessed via the Langendorff model of global 20 min ischemia and 30 min reperfusion. Oxidative stress parameters were determined spectrophotometrically from the samples of coronary venous effluent (O₂-, H₂O₂, TBARS, and NO₂-,) and heart tissue homogenate (TBARS, NO₂-, SOD, and CAT). H/E and Picrosirius red staining were used to examine cardiac architecture and cardiac collagen content. ME improved cardiodynamic parameters and achieved to preserve cardiac architecture after I/R injury and to decrease fibrosis, especially in the ME200 group compared to CTRL. ME200 and ME100 markedly decreased prooxidants TBARS, O₂-, and H₂O₂ while increasing NO₂-. Hereby, we confirmed the Melissa officinalis L. extract`s ability to save the heart from I/R induced damage, even after short-term preconditioning in terms of preserving cardiodynamic alterations, cardiac architecture, fibrosis, and suppressing oxidative stress, especially in dose of 200 mg/kg.

A 2017 review article Melissa officinalis L: "A Review Study With an Antioxidant Prospective" published in Journal Evidence Based Complementary Alternative Medicine by Sepide Miraj, Rafieian-Kopaei, Sara Kiani, was aimed not only to introduce Melissa officinalis (its growth condition, its chemical compounds, and its traditional usages) but also to overview its antioxidant properties in detail. This review was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases up to 2016. The search terms used were "Melissa officinalis L", "antioxidant properties, oxidative stress", "oxidative damage", "ROS". Articles whose full texts were not available were excluded from the study. In this study, firstly, traditional usage of this herb was reviewed, including antimicrobial activity (antiparasitic, antibacterial, antiviral, etc), antispasmodic, and insomnia properties. Then, its antioxidant properties were overviewed. Various studies have shown that Melissa officinalis L possesses high amount of antioxidant activity through its chemical compounds including high amount of flavonoids, rosmaric acid, gallic acid, phenolic contents. Many studies confirmed the antioxidative effects of Melissa officinalis; thus, its effect in preventing and treating oxidative stress-related diseases might be reliable.

In one study looking at how the antioxidants in Lemon Balm affect oxidative stress caused by low levels of radiation, Lemon Balm had remarkable results, including a significant improvement in blood levels of other antioxidant cells.

Another study that looked at supplementing the diet of medical professionals consistently exposed to low levels of radiation with Lemon Balm showed that it may be an effective way to protect them against unhealthy levels of oxidative stress. The study also showed Lemon Balm could naturally regulate a very important substance called superoxide dismutase. This enzyme, known in short as SOD, is vital to understand in terms of oxidative stress because the naturally occurring SOD can cause a number of different types of cell damage.