AB-free Kava reduces anxiety-like behavior without preventing nicotine-induced exploration suppression in mice
- 1Department of Psychiatry, College of Medicine, University of Florida
- 2Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), College of Pharmacy, University of Florida
Abstract
Introduction: Tobacco use is the leading preventable cause of death worldwide. Anxiety increases the risk for smoking, and smoking in turn increases the risk for anxiety disorders. There is therefore a need to identify interventions that reduce anxiety, in general and in the context of smoking. Kava (Piper methysticum), a natural product with a long history of indigenous use, has been shown to have anxiolytic and calming effects and reduce nicotine withdrawal. The current study examined whether kava without the hepatotoxic flavokavains A and B (AB-free) could reduce anxiety-like behavior in mice repeatedly treated with nicotine.
Methods: Male and female C57BL/6N mice received either a control diet or an AB-free kava-supplemented diet and underwent two blocks of nicotine treatments. Mice underwent a first block of five every-other-day injections of nicotine (0.5 mg/kg) or saline, with open field testing after each injection, followed 1 week later by a nicotine challenge. A second block of injections was given using the same injection schedule, followed by a second challenge 1 week later, and 2 weeks afterward mice received a final challenge in a novel open field.
Results: During the first treatment block, nicotine significantly reduced locomotor activity and center time. There was a significant diet × treatment interaction on center time, with AB-free kava significantly increasing center time in saline-treated but not nicotine-treated mice. During the final challenge in a novel open field, nicotine again significantly reduced locomotor activity and center time, and AB-free kava significantly increased center time irrespective of nicotine treatment, without affecting locomotor activity. These effects remained significant when cage was included as a random factor.
Discussion: These results suggest that AB-free kava has anxiolytic-like effects without reducing locomotor activity but does not prevent nicotine-induced suppression of exploratory behavior.
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BibTeX
@article{huisman2026abfree,
title = {{AB-free Kava reduces anxiety-like behavior without preventing nicotine-induced exploration suppression in mice}},
author = {Guido Huisman and Lara Caglayan and Tengfei Bian and Yifan Wang and Marcelo Febo and Chengguo Xing and Adriaan W. Bruijnzeel},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1981677},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1981677/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - AB-free Kava reduces anxiety-like behavior without preventing nicotine-induced exploration suppression in mice
AU - Guido Huisman
AU - Lara Caglayan
AU - Tengfei Bian
AU - Yifan Wang
AU - Marcelo Febo
AU - Chengguo Xing
AU - Adriaan W. Bruijnzeel
PY - 2026
DA - 2026/10/14
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1981677
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1981677/full
AB - Introduction: Tobacco use is the leading preventable cause of death worldwide. Anxiety increases the risk for smoking, and smoking in turn increases the risk for anxiety disorders. There is therefore a need to identify interventions that reduce anxiety, in general and in the context of smoking. Kava (Piper methysticum), a natural product with a long history of indigenous use, has been shown to have anxiolytic and calming effects and reduce nicotine withdrawal. The current study examined whether kava without the hepatotoxic flavokavains A and B (AB-free) could reduce anxiety-like behavior in mice repeatedly treated with nicotine. Methods: Male and female C57BL/6N mice received either a control diet or an AB-free kava-supplemented diet and underwent two blocks of nicotine treatments. Mice underwent a first block of five every-other-day injections of nicotine (0.5 mg/kg) or saline, with open field testing after each injection, followed 1 week later by a nicotine challenge. A second block of injections was given using the same injection schedule, followed by a second challenge 1 week later, and 2 weeks afterward mice received a final challenge in a novel open field. Results: During the first treatment block, nicotine significantly reduced locomotor activity and center time. There was a significant diet × treatment interaction on center time, with AB-free kava significantly increasing center time in saline-treated but not nicotine-treated mice. During the final challenge in a novel open field, nicotine again significantly reduced locomotor activity and center time, and AB-free kava significantly increased center time irrespective of nicotine treatment, without affecting locomotor activity. These effects remained significant when cage was included as a random factor. Discussion: These results suggest that AB-free kava has anxiolytic-like effects without reducing locomotor activity but does not prevent nicotine-induced suppression of exploratory behavior.
SN - 1663-9812
ER -