GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence
Abstract
Anxiety disorders are chronic and functionally disabling conditions with high psychological stress, characterised by cognitive symptoms of excessive worry and focus difficulties and physiological symptoms such as muscle tension and insomnia. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter within the central nervous system and is a key target of pharmacotherapies in the treatment of anxiety. Although current pharmaceutical treatments are often efficacious, they may cause undesirable side effects including cognitive decrements and withdrawal symptoms. Plant-based "phytomedicines" may provide novel treatment options, to act as an adjunctive or alternative to existing anxiolytic medications. As such, we conducted a systematic review to assess the current body of literature on anxiolytic phytomedicines and/or phytoconstituents. An open-ended search to 5 July 2017 was conducted using MEDLINE (PubMed), Scopus, and Cochrane library online databases and performed in a stepped format from preclinical to clinical investigations. Eligible studies must have had (a) in vitro evidence of GABA-modulating activity, (b) animal studies using anxiety models to test an anxiolytic effect, and (c) human clinical trials. Ten phytomedicines were identified as having preclinical investigations showing interaction with the GABA system, in addition to human clinical trials: kava, valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower, ashwagandha, skullcap, and lemon balm. Collectively, the literature reveals preclinical and clinical evidence for various phytomedicines modulating GABA-pathways, with comparative anxiolytic effect to the current array of pharmaceuticals, along with good safety and tolerability profiles.
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Anxiolytic effects are reported following administration of natural compounds and formulations derived from Piper methysticum (kava), Centella asiatica, Humulus lupulus, Ginkgo biloba, Matricaria chamomilla, Melissa officinalis, Passiflora incarnata, Scuterllaria leriflora, Valeriana officinalis, Withania somnifera, Magnolia officinalis and Lavendula angustifolia.
“Anxiolytic effects are reported following administration of natural compounds and formulations derived from Piper methysticum (kava), Centella asiatica (pennywort), Humulus lupulus (hops), Ginkgo biloba (maiden hair), Matricaria chamomilla (chamomile), Melissa officinalis (lemon balm), Passiflora incarnata (maypop), Scuterllaria leriflora (skullcap), Valeriana officinalis (valerian), Withania somn”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Savage, Firth, Stough, & Sarris, 2018
Modulation of the GABA system has been revealed as one important mechanism of several phytochemicals.
“However, modulation of the GABA system has been revealed as one important mechanism of several phytochemicals (Savage et al., 2018).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Savage et al., 2018
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- Authors
- Savage, K., Firth, J., Stough, C., & Sarris, J.
- Affiliations
- The University of Melbourne (AU)
- University of Manchester (GB)
- Swinburne University of Technology (AU)
- Corresponding author
- Savage, Karen
- Venue
- Phytotherapy Research
- Publisher
- Wiley
- Published
- 2017-11-23
- Volume
- 32
- Issue
- 1
- Pages
- 3-18
- ISSN
- 0951-418X (ISSN-L)
- 1099-1573
- OpenAlex
- W2770399954
- Cited by
- 131
- References
- 184
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 21 · 2022: 22 · 2021: 18 · 2020: 10 · 2019: 14 · 2018: 10
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytotherapy Research (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Keywords
- anxiety disorders, GABA, herbal medicine, kava, Valeriana officinalis, Humulus lupulus, chamomile, Ginkgo biloba, Passiflora, Withania somnifera, Scutellaria, lemon balm, GABA receptor modulation, anxiolytic efficacy, safety and tolerability
- MeSH terms
- Animals, Anxiety Disorders, Humans, Phytotherapy, GABA-A Receptor Agonists
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