Investigating the Hypnotic Effect of <i>Lactuca sativa</i> L. Seed in Patients with Insomnia: A Double-Blind, Randomized, Placebo-controlled Trial

Background: Lactuca sativa L. (garden lettuce), belonging to the Asteraceae family, is a leafy annual herb used for salads in Iran. The seeds of lettuce have traditionally been used as a sleeping aid and for relieving inflammation and osteodynia. In Persian medicine, the hypnotic effects of lettuce have been mentioned, and it has been introduced as one of the most effective sleep-inducing herbs. Objectives: The objective of the research was to investigate the hypnotic activity of L. sativa seed syrup in a double-blind, randomized, placebo-controlled trial. Methods: This investigation was a prospective double-blind randomized clinical trial performed at Golestan Hospital, Ahvaz, Iran. The lettuce seed syrup or placebo was prepared according to the pharmacopoeia Simple syrup formula. The criteria for diagnosing primary insomnia, as defined by the diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM-IV-TR), are mentioned in the following. In the study, participants were randomly assigned to either the lettuce group or placebo group in a 1:1 allocation ratio. Group 1 (n = 30) received 15 mL of lettuce seed syrup every night for 4 weeks, and group 2 (n = 30) was given 15 ml of a matching placebo. Each 15 mL of lettuce syrup contains 1 g aqueous extracts of L. sativa containing 111.16 mg total phenols as gallic acid equivalents (GAEs). Blinding was maintained for both the prescribing physician and the person presenting the lettuce seed syrup or placebo. Sleep quality was measured by subjective rating of the Pittsburgh Sleep Quality Index (PSQI), a self-noted questionnaire evaluating sleep quality subjectively over a one-month timeframe. The PSQI was assessed at the beginning and end of the clinical trial. Results: In the treatment group, the mean global score of the PSQI was 9.14 ± 2.13 at the beginning of the study (range: 7 - 15). After 4 weeks of lettuce seed syrup treatment, it was reduced to 4.74 ± 1.58 (range: 1 - 8). At the end of the study, the change in PSQI score was significant in patients compared to baseline (P ≤ 0.001). During treatment, no complaints or side effects were reported. The patients treated with L. sativa seed showed significantly greater improvement in Sleep Rating Scale scores compared to patients receiving placebo (P < 0.05). Conclusions: In conclusion, the syrup of lettuce seeds was found to be an effective sleeping aid.