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The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.<\/jats:p>","DOI":"10.3390\/nu15214586","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T09:27:28Z","timestamp":1698658048000},"page":"4586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neuroimaging Insights: Kava\u2019s (Piper methysticum) Effect on Dorsal Anterior Cingulate Cortex GABA in Generalized Anxiety Disorder"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8075-9222","authenticated-orcid":false,"given":"Karen","family":"Savage","sequence":"first","affiliation":[{"name":"Centre for Human Psychopharmacology, Swinburne University of Technology, 427-451 Burwood Road, Melbourne 3122, Australia"},{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne University, Melbourne 3121, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Sarris","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne University, Melbourne 3121, Australia"},{"name":"NICM Health Research Institute, Western Sydney University, Sydney 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hughes","sequence":"additional","affiliation":[{"name":"Centre for Mental Health, Swinburne University of Technology, Melbourne 3122, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-8696","authenticated-orcid":false,"given":"Chad A.","family":"Bousman","sequence":"additional","affiliation":[{"name":"Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, and Community Health Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rossell","sequence":"additional","affiliation":[{"name":"Centre for Mental Health, Swinburne University of Technology, Melbourne 3122, Australia"},{"name":"Mental Health, St Vincent\u2019s Hospital Melbourne, Melbourne 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4484-5462","authenticated-orcid":false,"given":"Andrew","family":"Scholey","sequence":"additional","affiliation":[{"name":"Centre for Human Psychopharmacology, Swinburne University of Technology, 427-451 Burwood Road, Melbourne 3122, Australia"},{"name":"Department of Nutrition, Dietetics and Food, Monash University, Melbourne 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3628-3220","authenticated-orcid":false,"given":"Con","family":"Stough","sequence":"additional","affiliation":[{"name":"Centre for Human Psychopharmacology, Swinburne University of Technology, 427-451 Burwood Road, Melbourne 3122, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Suo","sequence":"additional","affiliation":[{"name":"Brain Park, Turner Institute of Brain and Mind, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1001\/archpsyc.60.9.993","article-title":"Longitudinal Trajectories of Depression and Anxiety in a Prospective Community Study: The Zurich Cohort Study","volume":"60","author":"Merikangas","year":"2003","journal-title":"Arch. 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