Full-spectrum cannabidiol-rich oil modulates behavior and neurochemical alterations in a rodent model of maple syrup urine disease.

da Silva Lemos I.; Duarte S.; Morais M.; Alano C.; Quinsani L.; Matiola R.; Niero F.; Pedro L.; Réus Z.; Rigo F. et al. · Metabolic brain disease · 2026

**Background & Methods** This preclinical study evaluated full-spectrum cannabidiol (CBD)-rich oil in a branched-chain amino acid (BCAA)-induced rodent model of Maple Syrup Urine Disease (MSUD). Rats were divided into six groups receiving either control conditions, CBD monotherapy (3.5 or 7.5 mg/kg), BCAA induction alone, or BCAA induction with CBD co-treatment for 21 days, followed by behavioral testing and cerebral cortex analysis of cholinergic, inflammatory, and oxidative stress markers. **Key Findings** • **Cognitive Effects**: CBD treatment improved memory performance in object recognition testing, with the lower dose (3.5 mg/kg) showing improvements in both short- and long-term memory in healthy animals, while CBD 7.5 mg/kg and combined BCAA+CBD 3.5 mg/kg improved short-term memory only. • **Cholinergic System Restoration**: BCAA-induced disease reduced choline acetyltransferase (ChAT) activity; both CBD doses reversed this deficit. Additionally, CBD treatment normalized acetylcholinesterase (AChE) elevation seen in BCAA controls, with CBD 7.5 mg/kg producing ChAT levels exceeding controls. • **Anti-inflammatory & Antioxidant Effects**: CBD treatment reduced pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) elevated in BCAA controls. CBD also reversed oxidative stress markers including increased free radical formation and lipid peroxidation, while normalizing catalase activity reduced by BCAA induction. **Dosage & Administration** Two doses tested: 3.5 mg/kg and 7.5 mg/kg of full-spectrum CBD-rich oil administered for 21 days. Route of administration not specified. **Safety & Adverse Effects** Not reported. No adverse effects or safety parameters were documented in this preclinical study. **Evidence Quality** This is a preclinical rodent study with significant limitations restricting clinical applicability. The study does not represent human evidence, and findings require validation in clinical trials. The BCAA-induced MSUD model may not fully replicate the genetic disease phenotype. The authors acknowledge that optimal dosing and treatment duration remain undetermined. As a preclinical investigation, this study provides preliminary evidence supporting further investigation but cannot inform clinical practice without human data.

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