Pharmacokinetic and pharmacodynamic properties of cannabigerol in male mice

Alex Mabou Tagne; Faizy Ahmed; Adren Tran; Francesca Galvani; Lana Debbaneh; Emma Raine Perranoski; David Sarlah; Aditi Das; Elisa Pabon; Ziva Cooper; Daniele Piomelli

doi:10.1016/j.jpet.2026.104308

Pharmacokinetic and pharmacodynamic properties of cannabigerol in male mice

J Pharmacol Exp Ther. 2026 Apr;393(4):104308. doi: 10.1016/j.jpet.2026.104308. Epub 2026 Feb 24.

Authors

Affiliations

¹ Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, California; Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Science Center, Amarillo, Texas.
² Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, California.
³ Department of Chemistry, Rice University, Houston, Texas.
⁴ School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia.
⁵ Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
⁶ Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, California; Department of Biological Chemistry, University of California Irvine, Irvine, California; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California. Electronic address: piomelli@hs.uci.edu.

PMID: 41833244
DOI: 10.1016/j.jpet.2026.104308

Abstract

Cannabigerol (CBG) is a nonintoxicating phytocannabinoid gaining popularity as a self-medication for anxiety and other conditions; however, its pharmacological properties remain poorly defined. Here, we report the development of a rapid and sensitive liquid chromatography-tandem mass spectrometry method for quantifying CBG and its primary oxidative metabolite, cyclo-CBG. This platform enabled the characterization of CBG's pharmacokinetic and biotransformation profile after intraperitoneal administration (10 mg/kg) in male mice. CBG exhibited rapid systemic distribution and clearance, with relatively low brain penetration (brain-to-plasma ratio = 0.26). In contrast, cyclo-CBG accumulated in brain tissue to a surprising extent (brain-to-plasma ratio = 7.1), suggesting local formation and a potentially important role in mediating central effects. Despite prior reports of anxiolytic effects, we found that CBG administered at its peak brain concentration produced anxiogenic-like effects in mice, as assessed using the elevated plus maze. This response was not affected by the CB₁ cannabinoid receptor inverse agonist, rimonabant (3 mg/kg, i.p.), indicating a mechanism independent of CB₁ signaling. As interest in CBG continues to rise, the analytical and pharmacokinetic framework presented here provides a valuable foundation for advancing preclinical and clinical investigations into its efficacy, safety, and mechanism of action. SIGNIFICANCE STATEMENT: Application of a new liquid chromatography-tandem mass spectrometry method to quantify cannabigerol reveals key pharmacokinetic properties of this phytocannabinoid in mice, including unexpectedly high brain accumulation of its metabolite cyclo-cannabigerol, which was accompanied by anxiogenic-like effects. The results offer valuable tools for advancing preclinical and clinical investigations into cannabigerol pharmacology.

Keywords: Anxiety; Cannabigerol; Cannabis; Cyclo-cannabigerol; Liquid chromatography/tandem mass spectrometry; Pharmacokinetics.

MeSH terms

Animals
Anti-Anxiety Agents / pharmacokinetics
Anti-Anxiety Agents / pharmacology
Brain / drug effects
Brain / metabolism
Cannabinoids* / pharmacokinetics
Cannabinoids* / pharmacology
Chromatography, Liquid
Male
Mice
Mice, Inbred C57BL
Receptor, Cannabinoid, CB1 / metabolism
Tandem Mass Spectrometry / methods

Substances

Cannabinoids
cannabigerol
Anti-Anxiety Agents
Receptor, Cannabinoid, CB1