Work

AB-free Kava reduces anxiety-like behavior without preventing nicotine-induced exploration suppression in mice

Year: 2026

Type: article

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.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1981677