Toxicological profiling of Samrannitra: A traditional Thai Cannabis-based formulation evaluated following OECD guideline 408

Abstract

Samrannitra is a conventional Thai herbal preparation including Cannabis sativa L., traditionally utilized to mitigate insomnia, especially among the elderly. Due to its ability to modulate the central nervous system (CNS), assessing its safety profile is essential for clinical development. This study sought to evaluate the subchronic oral toxicity of Samrannitra in accordance with OECD Guideline No. 408, emphasizing pharmacodynamic safety and systemic tolerance. Male and female Sprague-Dawley rats were randomly allocated into four groups, receiving 0 (control), 40, 200, or 400 mg/kg/day of Samrannitra via oral gavage for a duration of 90 days. A supplementary satellite cohort was monitored for 28 days following therapy to evaluate any delayed or reversible effects. Clinical symptoms, mortality rates, food and water consumption, and body weight were assessed on a weekly basis. Hematological and biochemical markers were evaluated at the conclusion of the trial. Principal organs, including central nervous system tissues, were weighed and subjected to histological examination. No adverse effects associated to therapy were found at any dosage. Growth trajectories, behavioral assessments, and physiological functions were consistently within standard parameters. The hematological and biochemical values were analogous to those of the control group. Histopathological assessment indicated no central nervous system or systemic organ damage resulting from the treatment. Samrannitra exhibited no signs of systemic or organ-specific toxicity, including central nervous system-related effects, at dosages of up to 400 mg/kg/day. The No Observed Adverse Effect Level (NOAEL) was determined to be 400 mg/kg/day. These findings offer critical safety pharmacology data to facilitate the clinical application of Samrannitra as a standardized herbal treatment for insomnia.