Phase II randomized controlled trial comparing traditional Thai cannabis-based medicine with lorazepam for insomnia treatment

Abstract

Background: A traditional Thai cannabis-based multi-herbal formulation is legally recognized in Thailand for therapeutic use and clinical research. However, clinical evidence supporting its use for insomnia remains limited. Methods : This Phase II randomized, double-blind, active-controlled non-inferiority trial compared the efficacy and safety of the Anti-Pom-Leung Fever medicine with lorazepam in patients with chronic insomnia. One hundred participants were randomized to receive either the herbal formulation or lorazepam for 4 weeks. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Non-inferiority was evaluated at week 4 using a predefined margin of 2.1 based on the upper bound of the two-sided 95% confidence interval for the mean PSQI difference (experimental minus comparator). Longitudinal changes were analyzed using repeated-measures analysis of variance, and safety was evaluated through clinical and laboratory assessments. Results : Eighty-two participants completed the study (41 per group). Baseline characteristics were comparable between groups. Both treatments significantly improved sleep quality over 4 weeks. At week 4, mean PSQI scores were 3.44 in the experimental group and 4.78 in the comparator group, with a mean difference of -1.34 (95% CI: -2.99 to 0.31), demonstrating non-inferiority. A significant main effect of time on PSQI scores was observed, with no significant time-by-treatment interaction. Quality of life and stress improved in both groups, and safety profiles were comparable, with no clinically significant adverse effects. Conclusions : The traditional Thai cannabis-based multi-herbal formulation demonstrated non-inferior efficacy to lorazepam and was well tolerated, supporting its use as a short-term alternative for chronic insomnia.