Effect of Topical Lettuce (Lactuca sativa L.) Seed Oil on Childhood Sleep Disorders: a Randomized Double-Blind Controlled Trial

Document Type : Original paper


1 Department of Persian Medicine, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

3 Behavioral Sciences Research Center, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.


Background and objectives: Sleep disorders are among the most common complaints in childhood. Considering the pitfalls regarding safety and efficacy of conventional treatments for sleep disorders in children and based on the Persian medicine literature and results of recent animal and clinical investigations, this study was conducted to evaluate the effect of topical lettuce seed oil in these patients. Methods: The study was a double-blind randomized controlled trial in 3-6 years old children with sleep disorders. They were randomly assigned to receive either topical placebo oil and clonidine capsule or lettuce seed oil and placebo capsule for three weeks. Lettuce seed oil was prepared using cold press method. Persian version of “BEARS” pediatric sleep questionnaire was used before and after the intervention. Data analysis was performed using SPSS software (version 20) and pResults: At the end of study, 67 patients out of 72 completed the study. Similar to control group, children in intervention group significantly improved regarding bedtime issues (p<0.001), excessive daytime sleepiness (p=0.003), night awakenings (p=0.008), and problems in regularity and duration of sleep (p<0.001); however, no significant change was observed regarding the snoring in both groups. Conclusions: Topical use of lettuce seed oil on forehead and temporal areas of children could be considered as a safe and effective treatment for sleep disorders. However, further studies with larger sample size, longer duration of follow-up, and with the use of objective outcome measures are warranted.


Main Subjects

[1] Sheldon SH, Ferber R, Kryger MH. Principles and practice of pediatric sleep medicine. USA: Elsevier Health Sciences, 2005.
[2] Carter KA, Hathaway NE, Lettieri CF. Common sleep disorders in children. Am Fam Physician. 2014; 89(5): 368-377.
[3] Acebo C, Sadeh A, Seifer R, Tzischinsky O, Hafer A, Carskadon MA. Sleep/wake patterns derived from activity monitoring and maternal report for healthy 1-to 5-year-old children. Sleep. 2005; 28(12): 1568-1577.
[4] Meltzer LJ, Moore M. Sleep disruptions in parents of children and adolescents with chronic illnesses: prevalence, causes, and consequences. J Pediatr Psychol. 2008; 33(3): 279-291.
[5] Panaghi L, Kafashi A, Seraji M. Epidemiology of sleep disorders in primary school students in Tehran. Iran J Psychiatry Clin Psychol. 2004; 10(1): 50-58.
[6] Nafeiy Z, Shakiba M, Kashavarzian F. The prevalence of sleep disorders in 1 to 2 year infants refering to health centers in Yazd, 2008-2009. Toloo Behdasht. 2009; 8(26): 39-45.
[7] Ozgoli G, Sheikhan Z, Soleimani F, Nasiri M, Amiri S. Prevalence of sleep disorders among children 4-6 years old in Tehran province, Iran. Iran Red Crescent Med J. 2016; Article ID e22052.
[8] Khazaie T, Portaghali P, Jamali O, Khazaei S, Miri N, Sarhadi S, Moosavi S. Sleep pattern and common sleep problems of school children in Birjand. Modern Care. 2012; 9(3): 257-263.
[9] Wiener JM, Dulcan MK. Textbook of child and adolescent psychiatry. Arlington: American Psychiatric Publishing, 2004.
[10] Hashempur MH, Ghasemi MS, Daneshfard B, Ghoreishi PS, Lari ZN, Homayouni K, Zargaran A. Efficacy of topical chamomile oil for mild and moderate carpal tunnel syndrome: A randomized double-blind placebo-controlled clinical trial. Complement Ther Clin Pract. 2017; 26: 61-67.
[11] Sarris J, Byrne GJ. A systematic review of insomnia and complementary medicine. Sleep Med Rev. 2011; 15(2): 99-106.
[12] Atarzadeh F, Daneshfard B, Dastgheib L, Jaladat A, Amin G. Early description of diet induced blistering skin diseases in medieval Persia: Avicenna's point of view. Skinmed. 2016; 14(5): 367-370.
[13] Golshani SA, Daneshfard B, Mosleh G, Salehi A. Drugs and pharmacology in the Islamic Middle Era. Pharm Hist (Lond). 2015; 45(3): 64-69.
[14] Daneshfard B, Yekta NH, Khoshdel A, Heiran A, Cheraghi R, Yarmohammadi H. The effect of Delphinium denudatum (Jadwar) on fatigue: a randomized double blind placebo-controlled clinical trial. Complement Ther Med. 2019; 46: 29-35. 
[15] Nimrouzi M, Daneshfard B, Tafazoli V, Akrami R. Insomnia in traditional Persian medicine. Acta Med Hist Adriat. 2019; 17(1): 45-54.
[16] Petramfar P, Zarshenas MM, Moein M, Mohagheghzadeh A. Management of insomnia in traditional Persian medicine. Forsch Komplementmed. 2014; 21(2): 119-125.
[17] Feizi F, Namazi N, Rahimi R, Ayati MH. Medicinal plants for management of insomnia: a systematic review of animal and human studies. Galen. 2019; Article ID 1085.
[18] Keyhanmehr AS, Movahhed M, Sahranavard S, Gachkar L, Hamdieh M, Nikfarjad H. The effect of aromatherapy with Rosa damascena essential oil on sleep quality in children. Res J Pharmacongn. 2018; 5(1): 41-46.
[19] Ranjbar M, Salehi A, Rezaeizadeh H, Zarshenas MM, Sadeghniiat-Haghighi K, Mirabzadeh M, Firoozabadi A. Efficacy of a combination of Melissa officinalis L. and Nepeta menthoides Boiss. & Buhse on insomnia: a triple-blind, randomized placebo-controlled clinical trial. J Altern Complement Med. 2018; 24(12): 1197-1203.
[20] Feyzabadi Z, Rezaeitalab F, Badiee S, Taghipour A, Moharari F, Soltanifar A, Ahmadpour MR. Efficacy of violet oil, a traditional Iranian formula, in patients with chronic insomnia: a randomized, double-blind, placebo-controlled study. J Ethnopharmacol. 2018; 214: 22-28.
[21] Feyzabadi Z, Aliasl F, Qaraaty M, Aliasl J. Effective materia medica in treatment of insomnia in Iranian traditional medicine. Med Hist J. 2016; 7(23): 51-68.
[22] Kalantari T, Bahmani M, Heydari ST, Daneshfard B, Nematollahi Z, Nimrouzi M. Effect of temperament on happiness and job satisfaction in university employees. Pak J Med Health Sci. 2018; 12(2): 915-917.
[23] Pour ZS, Hosseinkhani A, Asadi N, Shahraki HR, Vafaei H, Kasraeian M, Bazrafshan K, Faraji A. Double-blind randomized placebo-controlled trial on efficacy and safety of Lactuca sativa L. seeds on pregnancy-related insomnia. J Ethnopharmacol. 2018; 227: 176-180.
[24] Owens JA, Dalzell V. Use of the ‘BEARS’sleep screening tool in a pediatric residents' continuity clinic: a pilot study. Sleep Med. 2005; 6(1): 63-69.
[25] Said S, Kashef HE, Mazar ME, Salama O. Phytochemical and pharmacological studies on Lactuca sativa seed oil. Fitoterapia. 1996; 67(3): 215-219.
[26] Ghorbani A, Rakhshandeh H, Sadeghnia HR. Potentiating effects of Lactuca sativa on pentobarbital-induced sleep. Iran J Pharm Res. 2013; 12(2): 401-406.
[27] Afsharypuor S, Ranjbar M, Mazaheri M, Shakibaei F, Aslani A. Analysis of fatty acid composition of crude seed oil of Lactuca sativa L. by GC-MS and GC methods. Trends Pharm Sci. 2018; 4(2): 95-98.
[28] Afsharypuor S, Ranjbar M, Mazaheri M, Shakibaei F, Aslani A. Essential oil constituents of seeds and fresh leaves of garden lettuce (Lactuca sativa L.) grown in Isfahan, Iran. Res J Pharmacogn. 2018; 5(3): 1-5.
[29] Dulcan MK, Ed. Dulcan's textbook of child and adolescent psychiatry. Arlington: American Psychiatric Publishing, 2015.
[30] Saghaei M. Random allocation software for parallel group randomized trials. BMC Med Res Method. 2004; Article ID 26.
[31] Mohammadi M, Ebrahim Amintehran MF, Ghaleh-bandi MRA, Shoaee S, Ghalehbaghi B. Reliability and validity of Persian version of “BEARS” pediatric sleep questionnaire. Indian J Sleep Med. 2008; 3(1): 14-19.
[32] Noumedem J, Djeussi D, Hritcu L, Mihasan M, Kuete V. Lactuca sativa.  In: Medicinal spices and vegetables from Africa. Kuete V, Ed. London: Academic Press, 2017.
[33] Khare CP. Indian herbal remedies: rational Western therapy, ayurvedic and other traditional usage, botany. Berlin: Springer, 2004.
[34] Nguyen M, Tharani S, Rahmani M, Shapiro M. A review of the use of clonidine as a sleep aid in the child and adolescent population. Clin Pediatr. 2014; 53(3): 211-216.
[35] MacLeod RL, Keen DV. Innovations in practice: 'off‐label' clonidine: UK pediatric and child and adolescent psychiatry prescribing practice for sleep problems. Child Adolesc Ment Health. 2014; 19(2): 147-150.
[36] Yakoot M, Helmy S, Fawal K. Pilot study of the efficacy and safety of lettuce seed oil in patients with sleep disorders. Int J Gen Med. 2011; 4: 451-456.
[37] Rakhshandeh H, Dolati K, Hamid RS, Ghorbani A. Effects of lettuce extracts on sleep in mice. Clin Biochem. 2011; 44(13): 116-117.
[38] Kim HD, Hong KB, Noh DO, Suh HJ. Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep. Food Sci Biotechnol. 2017; 26(3): 807-814.