Evaluation of sedative effects of an intranasal dosage form containing saffron, lettuce seeds and sweet violet in primary chronic insomnia: A randomized, double-dummy, double-blind placebo controlled clinical trial

Ethnopharmacological relevance: Traditional Persian Medicine (TPM) has been established as a valuable source of medicinal plants for the treatment of insomnia for thousands of years. Accordingly, oil extracts from plants' parts have been widely used to alleviate central nervous system (CNS) ailments including sleep disorders. A number of preparations have been recommended by TPM for the treatment of insomnia. Among them, an intranasal formulation containing oily macerates of Viola odorata L., Crocus sativus L. and Lactuca sativa L. stands out. Aim of the study: In the present double-dummy, double-blind placebo controlled clinical trial, we aim to evaluate the effectiveness of a combination of violet oil, saffron oil, and lettuce seeds oil nasal drop compared with the placebo (sesame oil). Materials and methods: Fifty patients with primary chronic insomnia were randomly assigned in TPM-treatment or placebo groups, received either two drops of the herbal oil or placebo into each nostril every noon and evening for 8 weeks. Before the study commencement and after 1, 4 and 8 weeks of treatment, Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires were completed by all patients. The primary outcome measure was considered as any changes in ISI scores between the first visit and after 8 weeks. Changes in PSQI scores during the study and possible side effects were also assessed. The multicompound herbal oil was standardized using HPLC analysis and contained 0.02 mg/mL crocin and 4 mu g/mL isoquercitrin. Results: Our study revealed a significant reduction in the ISI and PSQI scores from baseline by the study endpoint (P <= 0.01). The mean ISI scores in week 8 decreased significantly for the intervention group (P = 0.001) and also the placebo group (P < 0.01) when compared with baseline. Moreover, the use of hypnotic drugs in the intervention group was significantly reduced (P < 0.001), while in the control group was maintained at baseline level. Conclusions: It seems that intranasal use of the multi-herbal preparation can be used to improve chronic insomnia and to reduce the dose of conventional hypnotic medications in insomniac patients.