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Piper Methysticum (Kava) Attenuates Dorsal Anterior Cingulate Cortex GABA Levels in Generalised Anxiety Disorder

29 Pages Posted: 10 Mar 2023 Publication Status: Preprint

See all articles by Karen Savage

Karen Savage

Swinburne University of Technology

Jerome Sarris

Western Sydney University

Matthew Hughes

Swinburne University of Technology

Chad A. Bousman

University of Calgary

Susan L. Rossell

Swinburne University of Technology

Andrew Scholey

Swinburne University of Technology

Con Stough

Swinburne University of Technology

Chao Suo

Monash University

Abstract

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. 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 eight weeks’ 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 placebo, the Kava group had a significant reduction of dACC GABA (p = .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 inhibitory effect, which, if considered efficacious, suggests 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 dACC GABA levels previously un-examined in GAD could be utilised as a biomarker for diagnosis and treatment response.

Funding declaration: Data were derived from the larger KGAD clinical trial, funded by an Australian National Health and Medical Research Council (NHMRC) grant (No. APP1063383) and co-funded by Integria Healthcare. KS was the recipient of an Australian Government Research Training Program (RTP) Stipend Scholarship. The aforementioned grant and sponsor funding sources also provided support for research included in this manuscript to obtain a PhD (KS). JS was supported by NHMRC Clinical Research Fellowship (APP1125000). SLR holds a Senior National Health and Medical Research Council (NHMRC) Fellowship (GNT1154651).

Conflict of Interests: J.Sarris has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare & MediHerb (a kava product manufacturer), Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, Noetic Foundry, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Global Pharma Group, Australian Natural Therapeutics Group, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship, Medical Research Futures Fund. A Scholey has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Abbott Nutrition, Ārepa Nootropics, Arla Foods, Australian Research Council, Australian Wine Research Institute, Barilla, Bayer, Biotechnology and Biological Sciences Research Council, Blackmores, Coca Cola, Cognis, Cyvex, Dairy Health Innovation Consortium, Danone, Delica Therapeutics, DuPont, European Commission Framework 5 Research and Innovation initiative, Fonterra, Frutarom, GlaxoSmithKline, Ginsana, High Value Nutrition Fund, Kemin Foods, Martek, Masterfoods, National Health and Medical Research Council, Naturex, Nestlé, Neurobrands, Novartis, Nutricia-Danone, Pepsico, Pfizer, Pharmavite, Pharmaton, Red Bull, REVIV, Sanofi, Sen- Jam Pharmaceuticals, Verdure Sciences, Unilever, Wrigley Science Institute. He is Chief Scientific Officer for Ārepa Nootropics and is on the Scientific Advisory Board of Sen-Jam Pharmaceutical. All other authors have nothing to declare.

Ethical Approval: Approval from the University of Melbourne/Alfred Hospital, The University of Queensland, and Swinburne University’s Human Research Ethics Committee.

Trial Registration: This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study.

Keywords: anterior cingulate, GABA, Generalized Anxiety Disorder, Kava, magnetic resonance spectroscopy

Suggested Citation

Savage, Karen and Sarris, Jerome and Hughes, Matthew and Bousman, Chad A. and Rossell, Susan L. and Scholey, Andrew and Stough, Con and Suo, Chao, Piper Methysticum (Kava) Attenuates Dorsal Anterior Cingulate Cortex GABA Levels in Generalised Anxiety Disorder. Available at SSRN: https://ssrn.com/abstract=4348556 or http://dx.doi.org/10.2139/ssrn.4348556

Karen Savage (Contact Author)

Swinburne University of Technology ( email )

Cnr Wakefield and William Streets, Hawthorn Victor
3122 Victoria, 3122
Australia

Jerome Sarris

Western Sydney University ( email )

PO Box 10
Kingswood, 2747
Australia

Matthew Hughes

Swinburne University of Technology ( email )

Cnr Wakefield and William Streets, Hawthorn Victor
3122 Victoria, 3122
Australia

Chad A. Bousman

University of Calgary ( email )

University Drive
Calgary, T2N 1N4
Canada

Susan L. Rossell

Swinburne University of Technology ( email )

Cnr Wakefield and William Streets, Hawthorn Victor
3122 Victoria, Victoria 3122
Australia

Andrew Scholey

Swinburne University of Technology ( email )

Cnr Wakefield and William Streets, Hawthorn Victor
3122 Victoria, 3122
Australia

Con Stough

Swinburne University of Technology ( email )

Cnr Wakefield and William Streets, Hawthorn Victor
3122 Victoria, 3122
Australia

Chao Suo

Monash University ( email )

23 Innovation Walk
Wellington Road
Clayton, 3800
Australia

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