Tissue-specific untargeted 1H-NMR metabolomics reveals no adverse metabolic effects of daily intrabuccal cannabidiol (CBD) in healthy mice.

Masiphephethu M.; Bhengu S.; Venter K.; Lemmer Y.; Mason S. · Frontiers in pharmacology · 2026

**Background & Methods** This study employed untargeted 1H-NMR metabolomics to examine tissue-specific metabolic effects of cannabidiol (CBD) in Kramnik mice following 2 weeks of daily intrabuccal CBD administration. Brain, liver, and kidney tissues were analyzed using unsupervised principal component analysis (PCA) to detect metabolic alterations between CBD-treated and control groups. **Key Findings** • Minimal biological variation was detected between CBD-treated and control groups across all tissues examined, with unsupervised PCA revealing no significant metabolic clustering differences • Brain tissue showed the most notable changes, characterized by minor alterations in signaling and neuroenergetics pathways, while liver demonstrated modest changes in sugar metabolism and kidneys exhibited only minor fluctuations in phenylalanine levels • Overall metabolic profile suggested a more balanced metabolic state in CBD-treated mice with no evidence of adverse metabolic perturbations in any organ system studied **Dosage & Administration** Not reported. The abstract specifies daily intrabuccal administration for 2 weeks but does not provide specific dose quantities or concentrations. **Safety & Adverse Effects** No adverse metabolic effects were observed in brain, liver, or kidney tissues. The study found no evidence of metabolic toxicity or dysregulation in any examined organ system following CBD treatment. **Evidence Quality** This research represents a preclinical animal study with significant limitations. As a study conducted in mice (Kramnik strain), findings have limited direct translational applicability to human metabolism and pharmacokinetics. The study design appears to be descriptive rather than hypothesis-driven, relying on unsupervised statistical methods that may miss subtle metabolic changes without a priori defined comparisons. The 2-week treatment duration represents acute-to-subacute exposure and does not address long-term safety. No information regarding CBD dose conversion to human equivalents, pharmacokinetic parameters, or mechanistic follow-up studies is provided. The abstract lacks detail on sample sizes, statistical significance testing, and specific metabolite identifications beyond general metabolic pathways. While the findings suggest CBD's metabolic tolerability in this model, the evidence quality is preliminary and primarily suitable for hypothesis generation rather than clinical decision-making. Further studies with extended treatment duration, dose-response relationships, and validated human metabolomic investigations would be necessary to establish clinical safety profiles and therapeutic metabolic effects in human populations.

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