Life Extension Magazine®

Woman waking after sleeping and supplementing with lemon balm

Fall to Sleep Faster... Stay Sleeping Longer

Three plant-based extracts work on multiple sleep centers in the brain. A human study showed a remission of insomnia in 85% of subjects.

Scientifically reviewed by:  Julia Dosik, MPH, in August 2023. Written by: Katherine De Mateo.

The Centers for Disease Control and Prevention estimates that about 35% of adults get less sleep than they should.1

That’s part of the reason sleeping pills are so popular. But they come with serious drawbacks, including risk for physical dependence, accidents, and eventual tolerance that renders them ineffective.

Several plant-derived extracts have been found to safely help promote healthy sleep.

Scientists have created a combination of three such extracts: lemon balm, honokiol (a compound found in the magnolia tree), and apigenin (an ingredient found in chamomile).

Together, they work on multiple sleep centers in the brain to help restore healthy sleep patterns.

One study of people with mild-to-moderate anxiety disorders and sleep disturbances showed 85% of subjects that supplemented with lemon balm extract achieved full remission for insomnia and 70% of the subjects had complete relief of anxiety symptoms.2

Preclinical and clinical studies and gene expression analysis show that these ingredients can help people fall asleep more easily and improve sleep quality, leading to restorative and health-promoting rest.2-5

The Problem with Sleeping Pills

Woman in bed taking pills

Based on studies in sleep research, the CDC and other experts recommend that adults get seven or more hours of sleep a night.1,6

Using this standard, they found that more than 1 in 3 adults get suboptimal sleep on a regular basis. Frequently getting insufficient sleep has been linked to increased risk of obesity, depression, dementia, and chronic health issues like type II diabetes and heart disease.7-10

The failure to get enough sleep can be influenced by many factors, including caffeine consumption, stress, anxiety, and sleep disorders. The problem worsens with age, with around 40% of all elderly adults suffering from some form of sleep complaint.11,12 Changes in hormones as we grow older have been linked to insomnia and poor sleep quality,13,14 and some medications prescribed to older individuals can disrupt sleep.15

Pharmaceutical sleep aids are extremely popular, but they come with an array of problems. One group of drugs, the benzodiazepines , works by enhancing the effect of a calming neurotransmitter called gamma-aminobutyric acid (GABA). This causes reduction in anxiety, relaxation of muscles, and sedation. Common drugs in this class include Valium®, Xanax®, and Klonopin®.

But these drugs can cause too much sedation, leading to a “hangover” effect in the morning. Even worse, users can become addicted with regular use. And as doses increase, overdose becomes a possibility.16

Newer sleeping pills, such as Ambien® and Lunesta®, work by interacting with GABA receptors in the brain to produce sedative, anti-anxiety effects. Though they have a slightly lower risk for addiction, regular use can still lead to dependence. And many users of these drugs complain about a “zombie” effect the following day, which can cause poor mental performance, and risk for injuries such as falls.17,18

The newest class of sleep aids, orexin receptor antagonists, takes a different approach than the above-mentioned drugs that enhance GABA signaling. The orexin system in the brain controls wakefulness. Therefore, orexin receptor antagonists enhance sleep. Users of orexin receptor antagonists are subject to a “hangover” effect and the potential for physical dependence, like they are with most potent sleep aids.19

A Healthier Alternative

Lemon balm is an herb in the mint family that enhances GABA neurotransmitter activity in the brain, but by a different mechanism than benzodiazepines and other sleeping pills. The compounds in lemon balm, including rosmarinic acid, have been found to inhibit the enzyme that normally degrades GABA.4 This keeps GABA levels higher, to support a sleep-promoting and anxiety-reducing effect.

The magnolia tree is the source of a compound called honokiol. Research has shown that honokiol interacts with the receptor for GABA. Through this interaction, it boosts the activity of GABA to aid sleep.5

The flowering herb chamomile has long been used as a natural sleep aid. Part of this effect may also be attributed to its GABA-enhancing activity. But chamomile and its active components, particularly the nutrient apigenin, may act by additional mechanisms to further promote sleep.20

Computer-based gene expression analysis found that apigenin’s profile resembles an orexin receptor antagonist, and therefore may be working in a similar fashion.3 Orexin, made in the wake centers of the brain, is a compound that promotes wakefulness. A blocker of orexin, which apigenin may be, reduces wakefulness and promotes sleep.21,22

Medical Research on Herbal Sleep Aids

Scientists have uncovered evidence that lemon balm, honokiol, and chamomile can improve sleep.

Since they act by overlapping and unique mechanisms, a formulation combining all three can help restore healthy sleep patterns.

what you need to know

Promoting Restful Sleep

  • It’s estimated that more than 1 in 3 adults get inadequate sleep.
  • Lack of sleep is associated with risk for many chronic diseases, including obesity, type II diabetes, heart disease, depression, and more.
  • Medication used to induce sleep can lead to dependence and can have many potential side effects.
  • Several plant-derived compounds have similar sleep-supporting effects, but without the worrisome side effects.
  • A combination supplement of lemon balm, honokiol, and chamomile provides sleep-promoting effects to achieve a full night of restorative, health-protecting sleep.

Lemon Balm Extract

Lemon Balm

In one study, investigators recruited people with mild-to-moderate anxiety disorders and sleep disturbances.2 Subjects were given a lemon balm extract for 15 days, then assessed by rating scales for anxiety and depression that included sleep quality.

At the end of the study, all the subjects were considered to have had a positive response to the supplementation, with 85% seeing a full remission of their insomnia and the remaining 15% being much improved.

In terms of anxiety symptoms, 70% of subjects who responded to the product were considered in complete remission and another 25% experienced significant improvement.

Another study of lemon balm evaluated patients with heart disease who had trouble sleeping, along with high levels of depression, anxiety, and stress.23 These subjects were randomized to receive either a lemon balm supplement or a placebo for eight weeks.

The patients taking lemon balm had significantly reduced scores for depression, anxiety, and stress. They also took less time to fall asleep and had an increase in total sleep duration.


woman waking up well rested

In mouse models, honokiol reduced the time it took to fall asleep and increased the amount of sleep.24 In another animal study, honokiol was directly compared to diazepam (Valium®).25 It was found to reduce symptoms of anxiety to a similar level as the drug.

But while diazepam decreased muscle motor activity and tone, and impaired memory, honokiol did not. Mice experienced withdrawal symptoms when diazepam was stopped. The animals taking honokiol did not, indicating its use is not likely to lead to physical dependence.

Insufficient Sleep Impacts Health

Lack of sleep isn’t just an annoyance. It leads to serious problems for health and quality of life.

Inadequate sleep can have a harsh impact on cognitive function, causing slowed thinking, impaired attention, and inaccuracies that lead to loss of productivity during the day. It can also be downright dangerous. One study found that sleep deprivation led to poorer performance on cognitive and motor tasks comparable to a level of alcohol intoxication that would make it illegal to drive.29

Another study found that construction workers suffering from poor sleep were at greater risk for injuries at the workplace.30 And it’s been estimated that as many as 6,000 deaths due to car accidents per year have drowsy driving to blame.31

Sleep disorders affect long-term brain function as well. Repeated nights of inadequate sleep are associated with risk for mild cognitive impairment and dementia.11

Studies have also linked suboptimal sleep to obesity.32,33 Lack of sleep was found to cause abnormalities in levels of the hormones leptin and ghrelin, which are critically important to normal body fat balance.33 These abnormalities can contribute to weight gain and, eventually, obesity—which, in turn, increases the risk for many diseases.34-37

In fact, poor sleep quality has been implicated in risk for type II diabetes and heart disease.10,38 Even death from cancer appears more likely with inadequate sleep. One large study showed that patients with colorectal cancer who get less than five hours of sleep per day have a 54% increase in cancer mortality, compared to those getting seven to eight hours of sleep.39

All told, sleep can have a dramatic impact on mental and physical functioning and overall health.

Chamomile Extract


Chamomile is a popular herb often used as a tea to promote sleep and relaxation.26

In a rat study, chamomile was shown to improve sleep onset and had a mild hypnotic effect (much like benzodiazepines).27 In one clinical study, chamomile showed encouraging beneficial effects on daytime functioning in people with sleep problems.28

Researchers believe that the active components present in chamomile, apigenin in particular, are responsible for its effects.

New Tool in Drug Discovery

The newest frontier in drug discovery utilizes a bioinformatics approach called connectivity mapping to uncover previously unrecognized connections between compounds.

Whenever a compound or drug is applied to cells a unique gene expression signature is created. When two signatures are highly similar, this might represent useful and previously unrecognized connections between seemingly unrelated compounds.

This advanced tool, the Connectivity Map (CMap) library, was developed by the Broad Institute and is available for researchers to use.

Recently, scientists leveraged this tool to help identify natural compounds that produce a similar signature to an orexin receptor antagonist, a new class of sleep drugs. One such compound they identified was apigenin.

Although further investigation into this new potential mechanism is warranted, these interesting preliminary findings could help explain the complex nature of apigenin pharmacology in the brain.


Getting enough quality sleep is critical to health. Inadequate sleep increases risk for many chronic illnesses.

A large percentage of adults do not get enough sleep on a regular basis, and sleep problems increase with advancing age.

Many people rely on pharmaceutical drugs to aid sleep, but these medications cause several potential adverse effects, including risk for addiction and tolerance (which means they stop working).

A combination of plant-derived nutrients may provide support for healthy sleep, without the risk for significant side effects.

Lemon balm, honokiol, and chamomile (which contains apigenin) work on slumber centers in the brain to induce and maintain sleep, but without the sedating or addictive properties of those pharmaceutical medications.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


  1. Available at: Accessed May 9, 2019.
  2. Cases J, Ibarra A, Feuillere N, et al. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Med J Nutrition Metab. 2011 Dec;4(3):211-8.
  3. In-house connectivity mapping. LINCS-Broad Institute Database. Data on File. 2019.
  4. Awad R, Muhammad A, Durst T, et al. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother Res. 2009 Aug;23(8):1075-81.
  5. Alexeev M, Grosenbaugh DK, Mott DD, et al. The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA(A) receptors. Neuropharmacology. 2012 Jun;62(8):2507-14.
  6. Watson NF, Badr MS, Belenky G, et al. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015 Jun 1;38(6):843-4.
  7. Riemann D, Krone LB, Wulff K, et al. Sleep, insomnia, and depression. Neuropsychopharmacology. 2019 May 9.
  8. von Ruesten A, Weikert C, Fietze I, et al. Association of sleep duration with chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. PLoS One. 2012;7(1):e30972.
  9. Cooper CB, Neufeld EV, Dolezal BA, et al. Sleep deprivation and obesity in adults: a brief narrative review. BMJ Open Sport Exerc Med. 2018;4(1):e000392.
  10. Lao XQ, Liu X, Deng HB, et al. Sleep Quality, Sleep Duration, and the Risk of Coronary Heart Disease: A Prospective Cohort Study With 60,586 Adults. J Clin Sleep Med. 2018 Jan 15;14(1):109-17.
  11. Zhang F, Zhong R, Li S, et al. The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms. J Neural Transm (Vienna). 2017 May;124(5):559-68.
  12. Adib-Hajbaghery M, Mousavi SN. The effects of chamomile extract on sleep quality among elderly people: A clinical trial. Complement Ther Med. 2017 Dec;35:109-14.
  13. Geyer C. In Search of a Good Night’s Sleep: Hormones, Mind, Movement, and Breath. Am J Lifestyle Med. 2018 Mar-Apr;12(2):120-3.
  14. Baker FC, de Zambotti M, Colrain IM, et al. Sleep problems during the menopausal transition: prevalence, impact, and management challenges. Nat Sci Sleep. 2018;10:73-95.
  15. Sutton EL. Insomnia. Med Clin North Am. 2014 May;98(3):565-81.
  16. Available at: Accessed May 13, 2019.
  17. Frey DJ, Ortega JD, Wiseman C, et al. Influence of zolpidem and sleep inertia on balance and cognition during nighttime awakening: a randomized placebo-controlled trial. J Am Geriatr Soc. 2011 Jan;59(1):73-81.
  18. Chung SD, Lin CC, Wang LH, et al. Zolpidem Use and the Risk of Injury: A Population-Based Follow-Up Study. PLoS One. 2013;8(6):e67459.
  19. Available at: Accessed May 13, 2019.
  20. Awad R, Levac D, Cybulska P, et al. Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system. Can J Physiol Pharmacol. 2007 Sep;85(9):933-42.
  21. Brisbare-Roch C, Dingemanse J, Koberstein R, et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007 Feb;13(2):150-5.
  22. Dubey AK, Handu SS, Mediratta PK. Suvorexant: The first orexin receptor antagonist to treat insomnia. J Pharmacol Pharmacother. 2015 Apr-Jun;6(2):118-21.
  23. Haybar H, Javid AZ, Haghighizadeh MH, et al. The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clin Nutr ESPEN. 2018 Aug;26:47-52.
  24. Qu WM, Yue XF, Sun Y, et al. Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice. Br J Pharmacol. 2012 Oct;167(3):587-98.
  25. Kuribara H, Stavinoha WB, Maruyama Y. Honokiol, a putative anxiolytic agent extracted from magnolia bark, has no diazepam-like side-effects in mice. J Pharm Pharmacol. 1999 Jan;51(1):97-103.
  26. Sanchez-Ortuno MM, Belanger L, Ivers H, et al. The use of natural products for sleep: A common practice? Sleep Med. 2009 Oct;10(9):982-7.
  27. Shinomiya K, Inoue T, Utsu Y, et al. Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats. Biol Pharm Bull. 2005 May;28(5):808-10.
  28. Zick SM, Wright BD, Sen A, et al. Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: a randomized placebo-controlled pilot study. BMC Complement Altern Med. 2011 Sep 22;11:78.
  29. Williamson AM, Feyer AM. Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication. Occup Environ Med. 2000 Oct;57(10):649-55.
  30. Brossoit RM, Crain TL, Leslie JJ, et al. The effects of sleep on workplace cognitive failure and safety. J Occup Health Psychol. 2018 Nov 29.
  31. Available at: Accessed May 13, 2019.
  32. Gangwisch JE, Malaspina D, Boden-Albala B, et al. Inadequate sleep as a risk factor for obesity: analyses of the NHANES I. Sleep. 2005 Oct;28(10):1289-96.
  33. Taheri S, Lin L, Austin D, et al. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004 Dec;1(3):e62.
  34. Foley D, Ancoli-Israel S, Britz P, et al. Sleep disturbances and chronic disease in older adults: results of the 2003 National Sleep Foundation Sleep in America Survey. J Psychosom Res. 2004 May;56(5):497-502.
  35. Gislason T, Almqvist M. Somatic diseases and sleep complaints. An epidemiological study of 3,201 Swedish men. Acta Med Scand. 1987;221(5):475-81.
  36. Liu Y, Croft JB, Wheaton AG, et al. Association between perceived insufficient sleep, frequent mental distress, obesity and chronic diseases among US adults, 2009 behavioral risk factor surveillance system. BMC Public Health. 2013 Jan 29;13:84.
  37. Liu Y, Wheaton AG, Chapman DP, et al. Sleep duration and chronic diseases among U.S. adults age 45 years and older: evidence from the 2010 Behavioral Risk Factor Surveillance System. Sleep. 2013 Oct 1;36(10):1421-7.
  38. Spiegel K, Knutson K, Leproult R, et al. Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol (1985). 2005 Nov;99(5):2008-19.
  39. Xiao Q, Arem H, Pfeiffer R, et al. Prediagnosis Sleep Duration, Napping, and Mortality Among Colorectal Cancer Survivors in a Large US Cohort. Sleep. 2017 Apr 1;40(4).