select sleep supplement references
I spend a lot of time poring through the medical literature on the efficacy (or sometimes lack thereof) of herbs and supplements for sleep. As such, my poor computer often has a million zillion tabs open — and the only folks who benefit from this work are students who actually read the citations at the end of my powerpoints.
So, to support your education and my computer hygiene, I’m posting many of them here. (For studies related to health, mental health and climate change, check out NDClimate.org.)
Consider it a starting point for your own research — and please do share any cool new studies you find! If we’re not already connected by email, just shoot me a note from my contact page and sign up below to get my emails in your inbox.
Salúd!
—Dr. Orna
P.S. Wondering where to get these herbs and supplements? I’ve written up an herb-sourcing list here. For supplements, always use a reputable supplier rather than random online resellers. My go-to is Fullscript.
supplements
general
Imafuku, F., Yamamoto, K., Tanaka, E., Aoki, R., & Nishino, S. (2023). Analysis of the effects of known sleep-support supplements in relation to life habits, sleep conditions, and sleep problems. Nutrients, 15(10), 2377.
L-theanine
Baba, Y., Takihara, T., & Okamura, N. (2023). Theanine maintains sleep quality in healthy young women by suppressing the increase in caffeine-induced wakefulness after sleep onset. Food & Function, 14(15), 7109-7116.
Bulman, A., D’Cunha, N. M., Marx, W., Turner, M., McKune, A., & Naumovski, N. (2025). The effects of L-theanine consumption on sleep outcomes: A systematic review and meta-analysis. Sleep medicine reviews, 81, 102076.
Cotter, J., Caddick, C. E., Harper, J. L., & Ebajemito, J. K. (2026). Examining the effect of L-theanine on sleep: a systematic review of dietary supplementation trials. Nutritional Neuroscience, 29(2), 224-238.
Dasdelen, M. F., Er, S., Kaplan, B., Celik, S., Beker, M. C., & Orhan, C. (2022). A novel Theanine complex, Mg-l-Theanine improves sleep quality via regulating brain electrochemical activity. Front Nutr. 2022; 9.
Lim, S. E., Kim, H. S., Lee, S., Kang, E. Y., Lim, J. H., Kim, B. Y., … & Baek, Y. (2024). Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study. Frontiers in Nutrition, 11, 1419978.
Lyon, M. R., Kapoor, M. P., & Juneja, L. R. (2011). The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Alternative medicine review, 16(4), 348.
Sarris, J., Byrne, G. J., Cribb, L., Oliver, G., Murphy, J., Macdonald, P., … & Ng, C. H. (2019). L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial. Journal of psychiatric research, 110, 31-37.
herbs
Chamomilla recutita (chamomile)
Chang SM, Chen CH. Effects of an intervention with drinking chamomile tea on sleep quality and depression in sleep disturbed postnatal women: a randomized controlled trial. J Adv Nurs. 2016 Feb;72(2):306-15. doi: 10.1111/jan.12836. Epub 2015 Oct 20. PMID: 26483209.
Srivastava JK, Shankar E, Gupta S. Chamomile: A herbal medicine of the past with bright future. Mol Med Rep. 2010 Nov 1;3(6):895-901. doi: 10.3892/mmr.2010.377. PMID: 21132119; PMCID: PMC2995283.
Lavandula spp. (lavender)
Baldinger, Pia et al. Effects of Silexan on the serotonin-1A receptor and microstructure of the human brain: a randomized, placebo-controlled, double-blind, cross-over study with molecular and structural neuroimaging. The international journal of neuropsychopharmacology vol. 18,4 pyu063. 31 Oct. 2014,
Bazrafshan, M. R., Jokar, M., Shokrpour, N., & Delam, H. (2020). The effect of lavender herbal tea on the anxiety and depression of the elderly: A randomized clinical trial. Complementary therapies in medicine, 50, 102393.
Dold, Markus, et al. “Efficacy of Silexan in patients with anxiety disorders: a meta-analysis of randomized, placebo-controlled trials.” European Archives of Psychiatry and Clinical Neuroscience 273.7 (2023): 1615-1628.
Donelli, D., Antonelli, M., Bellinazzi, C., Gensini, G. F., & Firenzuoli, F. (2019). Effects of lavender on anxiety: A systematic review and meta-analysis. Phytomedicine : international journal of phytotherapy and phytopharmacology, 65, 153099.
Farshbaf-Khalili, Azizeh, Mahin Kamalifard, and Mahsa Namadian. “Comparison of the effect of lavender and bitter orange on anxiety in postmenopausal women: A triple-blind, randomized, controlled clinical trial.” Complementary therapies in clinical practice 31 (2018): 132-138.
Kasper, S., Anghelescu, I., & Dienel, A. (2015). Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep–A randomized, placebo-controlled trial. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 25(11), 1960–1967.
Kasper, S., Müller, W. E., Volz, H. P., Möller, H. J., Koch, E., & Dienel, A. (2018). Silexan in anxiety disorders: Clinical data and pharmacological background. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 19(6), 412–420.
Koulivand PH, Khaleghi Ghadiri M, Gorji A. Lavender and the nervous system. Evid Based Complement Alternat Med. 2013;2013:681304. doi: 10.1155/2013/681304. Epub 2013 Mar 14. PMID: 23573142; PMCID: PMC3612440.
Malcolm, B. J., & Tallian, K. (2018). Essential oil of lavender in anxiety disorders: Ready for prime time? The mental health clinician, 7(4), 147–155. https://doi.org/10.9740/mhc.2017.07.147
Nikfarjam M, Parvin N, Assarzadegan N, Asghari S. The Effects of Lavandula Angustifolia Mill Infusion on Depression in Patients Using Citalopram: A comparison Study. Iran Red Crescent Med J. 2013 Aug;15(8):734-9. doi: 10.5812/ircmj.4173. Epub 2013 Aug 5. PMID: 24578844; PMCID: PMC3918201.
O’Connor DW, Eppingstall B, Taffe J, van der Ploeg ES. A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia. BMC Complement Altern Med. 2013 Nov 13;13:315. doi: 10.1186/1472-6882-13-315. PMID: 24219098; PMCID: PMC3827620.
Roozbeh N, Ghazanfarpour M, Khadivzadeh T, Kargarfard L, Dizavandi FR, Shariati K. Effect of Lavender on Sleep, Sexual Desire, Vasomotor, Psychological and Physical Symptom among Menopausal and Elderly Women: A Systematic Review. J Menopausal Med. 2019;25(2):88-93. doi:10.6118/jmm.18158
Seifritz E, Kasper S, Möller HJ, Volz HP, Müller WE, Eckert A, Hatzinger M. Effect of anxiolytic drug silexan on sleep – a narrative review. World J Biol Psychiatry. 2022 Sep;23(7):493-500. doi: 10.1080/15622975.2021.2013092. Epub 2022 Oct 19. PMID: 36259937.
Seifritz E, Schläfke S, Holsboer-Trachsler E. Beneficial effects of Silexan on sleep are mediated by its anxiolytic effect. J Psychiatr Res. 2019 Aug;115:69-74. doi: 10.1016/j.jpsychires.2019.04.013. Epub 2019 Apr 17. PMID: 31121394.
Woelk H, Schläfke S. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine. 2010 Feb;17(2):94-9. doi: 10.1016/j.phymed.2009.10.006. Epub 2009 Dec 3. PMID: 19962288.
Yap WS, Dolzhenko AV, Jalal Z, Hadi MA, Khan TM. Efficacy and safety of lavender essential oil (Silexan) capsules among patients suffering from anxiety disorders: A network meta-analysis. Sci Rep. 2019 Dec 2;9(1):18042. doi: 10.1038/s41598-019-54529-9. PMID: 31792285; PMCID: PMC6889391.
Melissa officinalis (lemon balm)
Araj-Khodaei M, Noorbala AA, Yarani R, Emadi F, Emaratkar E, Faghihzadeh S, Parsian Z, Alijaniha F, Kamalinejad M, Naseri M. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression. BMC Complement Med Ther. 2020 Jul 3;20(1):207. doi: 10.1186/s12906-020-03003-5. PMID: 32620104; PMCID: PMC7333290.
Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG. 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):211-218. doi: 10.1007/s12349-010-0045-4. Epub 2010 Dec 17. PMID: 22207903; PMCID: PMC3230760.
Darvish-Mofrad-Kashani Z, Emaratkar E, Hashem-Dabaghian F, Emadi F, Raisi F, Aliasl J, Kamalinejad M, Hasheminejad SA, Eftekhar T, Zafarghandi N. Effect of Melissa officinalis (Lemon balm) on Sexual Dysfunction in Women: A Double- blind, Randomized, Placebo-controlled Study. Iran J Pharm Res. 2018 Winter;17(Suppl):89-100. PMID: 29796033; PMCID: PMC5958328.
Ghazizadeh J, Sadigh-Eteghad S, Marx W, Fakhari A, Hamedeyazdan S, Torbati M, Taheri-Tarighi S, Araj-Khodaei M, Mirghafourvand M. The effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials: A systematic review and meta-analysis. Phytother Res. 2021 Dec;35(12):6690-6705. doi: 10.1002/ptr.7252. Epub 2021 Aug 27. PMID: 34449930. (Abstract only.)
Haybar H, Javid AZ, Haghighizadeh MH, Valizadeh E, Mohaghegh SM, Mohammadzadeh A. 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. doi: 10.1016/j.clnesp.2018.04.015. Epub 2018 May 19. PMID: 29908682.
Kennedy, David O., et al. “Anxiolytic effects of a combination of Melissa ofcinalis and Valeriana ofcinalis during laboratory induced stress.” Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 20.2 (2006): 96-102.
Mathews IM, Eastwood J, Lamport DJ, Cozannet RL, Fanca-Berthon P, Williams CM. Clinical Efficacy and Tolerability of Lemon Balm (Melissa officinalis L.) in Psychological Well-Being: A Review. Nutrients. 2024 Oct 18;16(20):3545. doi: 10.3390/nu16203545. PMID: 39458539; PMCID: PMC11510126.
Zam W, Quispe C, Sharifi-Rad J, López MD, Schoebitz M, Martorell M, Sharopov F, Fokou PVT, Mishra AP, Chandran D, Kumar M, Chen JT, Pezzani R. An Updated Review on The Properties of Melissa officinalis L.: Not Exclusively Anti-anxiety. Front Biosci (Schol Ed). 2022 Jun 7;14(2):16. doi: 10.31083/j.fbs1402016. PMID: 35730441.
Passiflora spp. (passionflower)
Medina JH, Paladini AC, Wolfman C, Levi de Stein M, Calvo D, Diaz LE, Peña C. Chrysin (5,7-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties. Biochem Pharmacol. 1990 Nov 15;40(10):2227-31. doi: 10.1016/0006-2952(90)90716-x. PMID: 2173925.
Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality. Phytother Res. 2011 Aug;25(8):1153-9. doi: 10.1002/ptr.3400. Epub 2011 Feb 3. PMID: 21294203.
Nojoumi M, Ghaeli P, Salimi S, Sharifi A, Raisi F. Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study. Iran J Psychiatry. 2016 Jul;11(3):191-197. PMID: 27928252; PMCID: PMC5139955.
Wolfman C, Viola H, Paladini A, Dajas F, Medina JH. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav. 1994 Jan;47(1):1-4. doi: 10.1016/0091-3057(94)90103-1. PMID: 7906886.
Piper methysticum (kava)
Aporosa, S. Apo. “De-mythologizing and re-branding of kava as the new ‘world drug’of choice.” Drug Science, Policy and Law 5 (2019): 2050324519876131.
Bian, Tengfei et al. “Kava as a Clinical Nutrient: Promises and Challenges.” Nutrients vol. 12,10 3044. 5 Oct. 2020, doi:10.3390/nu12103044
Chua HC, Christensen ET, Hoestgaard-Jensen K, Hartiadi LY, Ramzan I, Jensen AA, Absalom NL, Chebib M. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLoS One. 2016 Jun 22;11(6):e0157700. doi: 10.1371/journal.pone.0157700. PMID: 27332705.
Fu, Peter P et al. “Toxicity of kava kava.” Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews vol. 26,1 (2008): 89-112. doi:10.1080/10590500801907407
Kuchta K, Hladikova M, Thomsen M, Nahrstedt A, Schmidt M. Kava (Piper methysticum) Extract for the Treatment of Nervous Anxiety, Tension and Restlessness. Drug Res (Stuttg). 2021 Feb;71(2):83-93. doi: 10.1055/a-1268-7135. Epub 2020 Nov 18. PMID: 33207379.
Lehrl S. Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. J Affect Disord. 2004 Feb;78(2):101-10. doi: 10.1016/s0165-0327(02)00238-0. Erratum in: J Affect Disord. 2004 Dec;83(2-3):287. PMID: 14706720.
Martin AC, Johnston E, Xing C, Hegeman AD. Measuring the chemical and cytotoxic variability of commercially available kava (Piper methysticum G. Forster). PLoS One. 2014 Nov 3;9(11):e111572. doi: 10.1371/journal.pone.0111572. PMID: 25365244.
Ooi SL, Henderson P, Pak SC. Kava for Generalized Anxiety Disorder: A Review of Current Evidence. J Altern Complement Med. 2018 Aug;24(8):770-780. doi: 10.1089/acm.2018.0001. Epub 2018 Apr 11. PMID: 29641222.
Pittler, M H, and E Ernst. “Kava extract for treating anxiety.” The Cochrane database of systematic reviews vol. 2003,1 (2003): CD003383. doi:10.1002/14651858.CD003383
Sarris, Jerome et al. “Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study.” The Australian and New Zealand journal of psychiatry vol. 54,3 (2020): 288-297. PMID: 31813230
Sarris J, Stough C, Bousman CA, Wahid ZT, Murray G, Teschke R, Savage KM, Dowell A, Ng C, Schweitzer I. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8. doi: 10.1097/JCP.0b013e318291be67. PMID: 23635869.
Sarris J, Kavanagh DJ, Byrne G, Bone KM, Adams J, Deed G. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl). 2009 Aug;205(3):399-407. doi: 10.1007/s00213-009-1549-9. Epub 2009 May 9. PMID: 19430766.
Smith, Katelyn, and Claudia Leiras. “The effectiveness and safety of Kava Kava for treating anxiety symptoms: A systematic review and analysis of randomized clinical trials.” Complementary therapies in clinical practice 33 (2018): 107-117.
Soares, Rita B et al. “An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava.” Journal of clinical medicine vol. 11,14 4039. 12 Jul. 2022, doi:10.3390/jcm11144039. PMID: 35887801
Steiner, G. G. “Kava as an anticraving agent: preliminary data.” Pacific Health Dialog 8.2 (2001): 335-339.
Tzeng YM, Lee MJ. Neuroprotective properties of kavalactones. Neural Regen Res. 2015 Jun;10(6):875-7. doi: 10.4103/1673-5374.158335. PMID: 26199594; PMCID: PMC4498339.
Yarnell, Eric. “The Safety of Piper Methysticum.” Botmed.rocks, 2023.
Tilia spp. (linden, basswood)
Aguirre-Hernández E, Martínez AL, González-Trujano ME, Moreno J, Vibrans H, Soto-Hernández M. Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice. J Ethnopharmacol. 2007 Jan 3;109(1):140-5. doi: 10.1016/j.jep.2006.07.017. Epub 2006 Jul 21. PMID: 16930893.
Allio A, Calorio C, Franchino C, Gavello D, Carbone E, Marcantoni A. Bud extracts from Tilia tomentosa Moench inhibit hippocampal neuronal firing through GABAA and benzodiazepine receptors activation. J Ethnopharmacol. 2015 Aug 22;172:288-96. doi: 10.1016/j.jep.2015.06.016. Epub 2015 Jul 2. PMID: 26144285.
Cárdenas-Rodríguez N, González-Trujano ME, Aguirre-Hernández E, Ruíz-García M, Sampieri A 3rd, Coballase-Urrutia E, Carmona-Aparicio L. Anticonvulsant and antioxidant effects of Tilia americana var. mexicana and flavonoids constituents in the pentylenetetrazole-induced seizures. Oxid Med Cell Longev. 2014;2014:329172. doi: 10.1155/2014/329172. Epub 2014 Aug 13. PMID: 25197430; PMCID: PMC4147264.
De Simone M, De Feo R, Choucha A, Ciaglia E, Fezeu F. Enhancing Sleep Quality: Assessing the Efficacy of a Fixed Combination of Linden, Hawthorn, Vitamin B1, and Melatonin. Med Sci (Basel). 2023 Dec 28;12(1):2. doi: 10.3390/medsci12010002. PMID: 38249078; PMCID: PMC10801487.
Herrera-Ruiz M, Román-Ramos R, Zamilpa A, Tortoriello J, Jiménez-Ferrer JE. Flavonoids from Tilia americana with anxiolytic activity in plus-maze test. J Ethnopharmacol. 2008 Jul 23;118(2):312-7. doi: 10.1016/j.jep.2008.04.019. Epub 2008 Apr 24. PMID: 18539420.
Pérez-Ortega, G., et al. “Sedative and anxiolytic efficacy of Tilia americana var. mexicana inflorescences used traditionally by communities of State of Michoacan, Mexico.” Journal of Ethnopharmacology 116.3 (2008): 461-468.
Viola H, Wolfman C, Levi de Stein M, Wasowski C, Peña C, Medina JH, Paladini AC. Isolation of pharmacologically active benzodiazepine receptor ligands from Tilia tomentosa (Tiliaceae). J Ethnopharmacol. 1994 Aug;44(1):47-53. doi: 10.1016/0378-8741(94)90098-1. PMID: 7990504. (Abstract.)
Withania somnifera (ashwagandha)
Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian journal of psychological medicine, 34(3), 255–262.
Cheah KL, Norhayati MN, Husniati Yaacob L, Abdul Rahman R. Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis. Plos one. 2021 ;16(9):e0257843. DOI: 10.1371/journal.pone.0257843. PMID: 34559859; PMCID: PMC8462692.
Gannon, J. M., Forrest, P. E., & Roy Chengappa, K. N. (2014). Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder. Journal of Ayurveda and integrative medicine, 5(4), 241–245.
Langade D, Kanchi S, Salve J, et al. (September 28, 2019) Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study. Cureus 11(9): e5797.
Lopresti, A. L., Smith, S. J., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine, 98(37), e17186.