Anxiety

Multiple double-blind, placebo-controlled RCTs and ≥4 meta-analyses show standardised root extract lowers perceived stress, Hamilton-Anxiety scores and serum cortisol in adults, via HPA-axis down-regulation and GABA-A modulation ^{1,2,3,4Reference 1Akhgarjand C et al. · 2022Meta-analysisDoes Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? — systematic review and meta-analysis of randomised controlled trialsView study →Reference 2Arumugam V et al. · 2024Meta-analysisEffects of Ashwagandha (Withania somnifera) on stress and anxiety — systematic review and meta-analysisView study →Reference 3Lopresti AL et al. · 2019RCTStress-relieving and pharmacological actions of an ashwagandha extract — a randomised, double-blind, placebo-controlled studyView study →Reference 4Chandrasekhar K et al. · 2012RCTA prospective, randomised double-blind, placebo-controlled study of a high-concentration full-spectrum ashwagandha root extract in reducing stress and anxiety — RCTView study →}. Effect sizes are heterogeneous and trials short (6–10 weeks) on proprietary extracts (KSM-66, Shoden) — not the whole herb, with no head-to-head against first-line anxiolytics.

Anxiety is chamomile’s strongest human indication. A double-blind placebo-controlled RCT in 57 GAD outpatients found a standardised extract (1.2% apigenin, ~220–1100 mg/day) significantly reduced total Hamilton Anxiety score over 8 weeks (P = 0.047) ^{28Reference 28Amsterdam JD et al. · 2009RCTA randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder — randomised controlled trialView study →}, and it now features in an anxiety network meta-analysis alongside kava and lavender ^{29Reference 29Zhang W et al. · 2022Meta-analysisMedicinal herbs for the treatment of anxiety: a systematic review and network meta-analysisView study →}.

The effect is modest, confined to a specific standardised capsule (not tea), and the larger relapse-prevention trial’s primary endpoint was non-significant ^{30Reference 30Mao JJ et al. · 2016RCTLong-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trialView study →}.

Anxiety is kava’s best-evidenced indication. An early meta-analysis of seven double-blind RCTs found extract superior to placebo (~9.7-point drop on the Hamilton Anxiety scale) and a Cochrane review of 11 trials (645 participants) confirmed a smaller but significant benefit, most likely via positive allosteric modulation of GABA-A receptors by kavain plus MAO-B and monoamine-reuptake effects ^{55,56,57,58,59,60,61,62Reference 55Pittler et al. · 2000Meta-analysisEfficacy of kava extract for treating anxiety — systematic review and meta-analysisView study →Reference 56Pittler et al. · 2003Systematic reviewKava extract for treating anxiety — systematic reviewView study →Reference 57Sarris et al. · 2009RCTThe Kava Anxiety Depression Spectrum Study (KADSS) — a randomised, placebo-controlled crossover trialView study →Reference 58Boerner et al. · 2003RCTKava-Kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder — an 8-week randomised, double-blind multicentre RCT in 129 outpatientsView study →Reference 59Ooi et al. · 2018Meta-analysisKava for generalized anxiety disorder — a review and meta-analysis of current evidence [systematic review]View study →Reference 60Sarris et al. · 2011ReviewKava — a comprehensive review of efficacy, safety, and psychopharmacology [review]View study →Reference 61Chua et al. · 2016In vitroKavain, the major constituent of the anxiolytic kava extract, potentiates GABA-A receptors — functional characteristics and molecular mechanism [in vitro]View study →Reference 62Jussofie et al. · 1994AnimalKavapyrone-enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain [animal]View study →}.

The signal is strongest for short-term, situational, non-clinical anxiety. The largest, longest and most rigorous trial (16-week phase III, n=171, diagnosed GAD) was null ^{63Reference 63Sarris et al. · 2020RCTKava for generalised anxiety disorder — a 16-week double-blind, randomised, placebo-controlled study [phase III RCT]View study →}.

Kava carries a rare risk of idiosyncratic hepatotoxicity. Aqueous extracts of peeled noble-cultivar root are the preferred form, and kava is not combined with alcohol ^{64Reference 64Teschke · 2010ReviewKava hepatotoxicity — a clinical review [review]View study →}.

The oral lavender-oil softgel Silexan (standardised L. angustifolia essential oil, 80–160 mg/day) beat placebo on the Hamilton Anxiety scale in subsyndromal anxiety ^{68Reference 68Kasper et al. · 2010RCTSilexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder — randomized, double-blind, placebo-controlled trialView study →} and generalised anxiety disorder ^{69Reference 69Kasper et al. · 2014RCTLavender oil preparation Silexan is effective in generalized anxiety disorder — a randomized, double-blind comparison to placebo and paroxetineView study →}, was non-inferior to 0.5 mg lorazepam ^{70Reference 70Woelk et al. · 2010RCTA multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder — randomized controlled trialView study →} and comparable to paroxetine, and produced no withdrawal/rebound on abrupt discontinuation ^{71Reference 71Gastpar et al. · 2017RCTSilexan does not cause withdrawal symptoms even when abruptly discontinued — randomized controlled trialView study →}; a network and a pooled meta-analysis confirm a consistent moderate anxiolytic effect ^{72,73Reference 72Yap et al. · 2019Meta-analysisEfficacy and safety of lavender essential oil (Silexan) capsules among patients suffering from anxiety disorders — network meta-analysisView study →Reference 73Dold et al. · 2023Meta-analysisEfficacy of Silexan in patients with anxiety disorders — a meta-analysis of randomized, placebo-controlled trialsView study →}.

All the positive data are for one manufacturer’s concentrated oral capsule — not the 1:2 tincture, the dried-flower tea, or a diffuser at the same strength.

Two controlled trials in patients with advanced/life-threatening cancer found single-session psilocybin produced substantial, sustained decreases in anxiety and depression ^{85,86Reference 85Bogenschutz et al. · 2022RCTPercentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in Alcohol Use Disorder — randomised controlled trialView study →Reference 86Bogenschutz et al. · 2015Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept studyView study →}. The anxiety endpoint is specifically existential distress in serious illness, not generalised anxiety disorder — outcomes hinge on screening, preparation and integration, not the drug alone.

Anxiety is lemon balm’s best-supported indication. A 2021 systematic review and meta-analysis of clinical trials found lemon balm significantly reduced anxiety scores versus placebo (SMD −0.98), with acute placebo-controlled crossover work showing a single standardised dose raised self-rated calmness, plausibly via GABA-transaminase inhibition by rosmarinic acid and the triterpenes ursolic/oleanolic acid ^{92,93,94,95,96Reference 92Ghazizadeh J et al. · 2021Meta-analysisThe effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials — a systematic review and meta-analysisView study →Reference 93Kennedy DO et al. · 2002RCTModulation of mood and cognitive performance following acute administration of Melissa officinalis — randomised placebo-controlled crossover trialView study →Reference 94Kennedy DO et al. · 2006RCTAnxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory-induced stress — randomised placebo-controlled crossover trialView study →Reference 95Ibarra A et al. · 2010AnimalEffects of chronic administration of Melissa officinalis extract on anxiety-like reactivity in mice — animal modelView study →Reference 96Awad R et al. · 2009In vitroBioassay-guided fractionation of lemon balm using an in vitro measure of GABA transaminase activity — in vitroView study →}.

Trials are small and use different standardised extracts, the dose-response is non-linear (highest doses paradoxically increased anxiety in one session), and few measure physiological stress markers.

Multiple small human RCTs support P. incarnata for anxiety: a pilot double-blind trial (n=36) matched oxazepam 30 mg/day for GAD over four weeks with less job-performance impairment ^{108Reference 108Akhondzadeh et al. · 2001RCTPassionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam — randomisedView study →}, and pre-operative and dental-extraction trials find oral extract (500 mg / 260 mg) comparable to midazolam for situational anxiety without added sedation ^{109,110,111,112,113Reference 109Movafegh et al. · 2008RCTPreoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study — randomised, placebo-controlledView study →Reference 110Aslanargun et al. · 2012RCTPassiflora incarnata Linneaus as an anxiolytic before spinal anesthesia — randomised, placebo-controlledView study →Reference 111Dantas et al. · 2017RCTEffects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction — randomised, double-blind crossoverView study →Reference 112Lima Neto et al. · 2025RCTEffects of Passiflora incarnata on salivary biomarkers and anxiety in patients undergoing third molar extraction surgery — randomised, placebo-controlledView study →Reference 113Christoffoli et al. · 2021RCTAssessment of Passiflora incarnata L for conscious sedation during extraction of mandibular third molars — randomised, double-blind crossoverView study →}, via GABA_A modulation ^{114,115Reference 114Elsas et al. · 2010In vitroPassiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo — in vitro / animal modelView study →Reference 115Appel et al. · 2011In vitroModulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. — in vitroView study →}. A 2007 Cochrane review and 2022 network meta-analysis judge the effect real but low-certainty — trials are small, single-centre, and use different proprietary extracts ^{116,29Reference 116Miyasaka et al. · 2007Systematic reviewPassiflora for anxiety disorder — systematic review (Cochrane)View study →Reference 29Zhang W et al. · 2022Meta-analysisMedicinal herbs for the treatment of anxiety: a systematic review and network meta-analysisView study →}.

Human anxiolytic signals exist but come from secondary outcomes, not dedicated trials: in Calabrese’s elderly cognition RCT, combined state+trait anxiety and heart rate fell on Bacopa and rose on placebo ^{5Reference 5Calabrese et al. · 2008RCTEffects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly — randomised, double-blind, placebo-controlled trialView study →}, and an acute crossover (n=17) of CDRI 08 lowered salivary cortisol and improved mood during a stress challenge ^{6Reference 6Benson et al. · 2014RCTAn acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood — randomised controlled trialView study →}. Preclinically it normalised HPA-axis markers in prenatally stressed rats ^{7Reference 7Sivasangari et al. · 2020AnimalStandardized Bacopa monnieri extract ameliorates learning and memory impairments through synaptic protein, neurogranin, BDNF signaling, and HPA axis in prenatally stressed rat offspring — animal modelView study →}. No adequately powered RCT has used anxiety as the primary endpoint. Traditional Ayurvedic use for anxiety predates all of this ^{8Reference 8Chopra · 1958Chopra’s Indigenous Drugs of India}.

Anxiety is California poppy’s best-supported use. In mice an aqueous extract produced an anticonflict effect at a low dose (25 mg/kg) separable from sedation, and both anxiolytic and sedative effects were abolished by flumazenil — implicating the benzodiazepine site of the GABAA receptor, with (S)-reticuline as a positive allosteric modulator and N-methyllaurotetanine adding 5-HT1A affinity ^{18,19,20,21Reference 18Fedurco M et al. · 2015Modulatory effects of Eschscholzia californica alkaloids on recombinant GABAA receptorsView study →Reference 19Gafner S et al. · 2006In vitroAlkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-OH-DPAT to 5-HT1A receptors in vitroView study →Reference 20Rolland A et al. · 1991Behavioural effects of the American traditional plant Eschscholzia californica: sedative and anxiolytic propertiesView study →Reference 21Rolland A et al. · 2001Neurophysiological effects of an extract of Eschscholzia californica ChamView study →}.

The only RCT (n=264, 3 months) tested a fixed combination of California poppy, hawthorn and magnesium (Sympathyl) against placebo in mild-to-moderate GAD, finding a modest but significant advantage on the Hamilton anxiety score ^{22Reference 22Hanus M et al. · 2004RCTDouble-blind, randomised, placebo-controlled study of a fixed combination of Crataegus oxyacantha and Eschscholtzia californica and magnesium in mild-to-moderate anxietyView study →}. No published trial has tested the herb alone in humans, so its individual contribution and monotherapy dose are unknown.

The calming effect belongs to cannabidiol, not the whole plant — in a double-blind RCT a single 600 mg oral CBD dose reduced anxiety during a simulated public-speaking test in social-anxiety patients ^{23Reference 23Bergamaschi et al. · 2011RCTCannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients — randomised controlled trialView study →}, with smaller acute-dosing studies agreeing. But the effect showed at 300–600 mg CBD (far above the 10–50 mg in retail products), there is no chronic-treatment RCT, and high-THC cannabis can provoke anxiety and paranoia.

A double-blind RCT (n=40) found a single 12 g oral dose attenuated the acoustic startle response (a validated anxiety marker) 30–60 min post-dose without affecting mood/HR/BP ^{36Reference 36Bradwejn et al. · 2000RCTA double-blind, placebo-controlled study on the effects of Gotu Kola on acoustic startle response in healthy subjects — randomised trialView study →}; a small open-label GAD study (500 mg 2×/day, 60 days) reported reduced anxiety/stress/depression scores ^{37Reference 37Jana et al. · 2010Clinical trialA clinical study on the management of generalized anxiety disorder with Centella asiatica — clinical trialView study →}. The data are mostly acute and single-dose, with no adequately powered RCT of sustained treatment of a diagnosed disorder.

In a challenge-model RCT, 200 mg L-5-HTP blunted the reaction to a 35% CO₂ panic challenge in panic-disorder patients ^{38Reference 38Schruers K et al. · 2002RCTAcute L-5-hydroxytryptophan administration inhibits carbon-dioxide-induced panic in panic disorder patients — randomised controlled trialView study →}, and Griffonia seed extract itself (10 and 25 mg/kg) also increased time in the light compartment in a rat dark–light test ^{39Reference 39Carnevale G et al. · 2011AnimalAnxiolytic-like effect of Griffonia simplicifolia Baill. seed extract in rats — animal modelView study →}.

The human data are a single acute challenge model rather than a treatment trial, and the direct-herb evidence is rodent-only — with a companion rat study flagging reduced sexual behaviour at higher doses ^{40Reference 40Carnevale G et al. · 2010AnimalGriffonia simplicifolia negatively affects sexual behavior in female rats — animal modelView study →}.

A controlled trial in generalised anxiety disorder (Ocimum sanctum leaf, 500 mg twice daily, 60 days, n=35) reported significant falls in anxiety, stress and depression scores ^{42Reference 42Bhattacharyya et al. · 2008Clinical trialControlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders — controlled clinical trialView study →}, consistent with RCTs on stress symptoms ^{43,44Reference 43Saxena et al. · 2012RCTEfficacy of an extract of Ocimum tenuiflorum (OciBest) in the management of general stress — randomised placebo-controlled trialView study →Reference 44Lopresti et al. · 2022RCTA randomised, double-blind, placebo-controlled trial investigating the effects of a standardised Ocimum tenuiflorum extract — randomised controlled trialView study →}. The GAD trial was small, not placebo-controlled and relied on self-report scales, and no large or long confirmatory study exists.

Beyond sedation, one small randomised, placebo-controlled, double-blind crossover pilot (n=36 healthy young adults with at least mild baseline symptoms) found a hops dry-extract supplement over two 4-week periods reduced self-reported depression, anxiety and stress on DASS-21, with morning cortisol measured ^{45Reference 45Kyrou I et al. · 2017RCTEffects of a hops (Humulus lupulus L.) dry extract supplement on self-reported depression, anxiety and stress levels in apparently healthy young adults: a randomized, placebo-controlled, double-blind, crossover pilot study — [randomized]View study →}. The trial is unreplicated and small, in a subclinical (non-diagnosed) population, with no dose-finding and no active-comparator arm.

The broader anxiety rationale also leans on hops’ sedative, GABAergic sleep evidence ^{46,47,48Reference 46Morin CM et al. · 2005RCTValerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial — [randomized]View study →Reference 47Schicktanz N et al. · 2025RCTEffects of a Valerian-Hops Extract Combination (Ze 91019) on Sleep Duration and Daytime Cognitive and Psychological Parameters in Occasional Insomnia: A Randomized Controlled Feasibility Trial — [randomized]View study →Reference 48Franco L et al. · 2012The sedative effects of hops (Humulus lupulus), a component of beer, on the activity/rest rhythm — [animal]View study →}.

Jasmine acts most clearly in people as an aroma. Inhaling jasmine odour blunted the stress-induced rise in diastolic blood pressure by ~a quarter ^{49Reference 49Nagai M et al et al. · 2000Clinical trialPleasant odors attenuate the blood pressure increase during rhythmic handgrip in humans — [human study]View study →}, and jasmine-tea odour / its component linalool at low intensity slowed heart rate, raised parasympathetic HRV and lifted calm-vigorous mood ^{50,51Reference 50Inoue N et al et al. · 2003Autonomic nervous responses according to preference for the odor of jasmine tea — [human autonomic study]View study →Reference 51Kuroda K et al et al. · 2005Clinical trialSedative effects of the jasmine tea odor and (R)-(-)-linalool, one of its major odor components, on autonomic nerve activity and mood states — [human study]View study →}; a 2024 single-blind placebo-controlled trial reported reduced anxiety in children during dental procedures ^{52Reference 52Jafarzadeh Samani M et al et al. · 2024RCTAnxiolytic Effect of Jasmine Aromatherapy in Pediatric Dental Procedures: A Single-Blinded Randomized Placebo-Controlled Trial — [randomised placebo-controlled trial]View study →}.

The effect is bidirectional: topical J. sambac aromatherapy instead raised breathing rate, blood pressure and alertness (a stimulant profile) ^{53Reference 53Hongratanaworakit T · 2010Stimulating effect of aromatherapy massage with jasmine oil — [human aromatherapy study]View study →} — so it is an aroma effect whose direction depends on dose, preference and context, not a reliably calming ingested anxiolytic.

A single-dose fMRI study found 25 mg Zembrin reduced amygdala reactivity to threat and weakened amygdala–hypothalamus coupling, consistent with a calmer, more regulated stress response ^{54Reference 54Terburg et al. · 2013RCTAcute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala — randomised, placebo-controlled pharmaco-fMRI crossoverView study →}. The study was small and single-dose, measured imaging only with no anxiety-scale or clinical outcome, and used the proprietary Zembrin extract rather than the whole herb.

In a 2019 study in overweight and obese adults, lion’s mane reduced anxiety and sleep disturbance over 8 weeks ^{83Reference 83Vigna et al. · 2019Clinical trialHericium erinaceus improves mood and sleep disorders in patients affected by overweight or obesity — controlled trialView study →}, and a mouse model showed reduced anxiety-like behaviour via hippocampal neurogenesis ^{84Reference 84Ryu et al. · 2018AnimalHericium erinaceus extract reduces anxiety and depressive behaviors by promoting hippocampal neurogenesis in the adult mouse brain — animal modelView study →}. Anxiety was a secondary endpoint in one specific population, not a primary anxiety-disorder trial.

Anxiety is the only magnolia indication with human trials. A standardised Magnolia officinalis + Phellodendron amurense blend (Relora, ~750 mg/day, 4–6 wk) lowered salivary cortisol ~18% and reduced transient (state) anxiety and stress-related mood indices in small placebo-controlled RCTs ^{87,88,89Reference 87Talbott et al. · 2013RCTEffect of Magnolia officinalis and Phellodendron amurense (Relora) on cortisol and psychological mood state in moderately stressed subjects — randomised placebo-controlled trialView study →Reference 88Kalman et al. · 2008RCTEffect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women — randomised placebo-controlled trialView study →Reference 89Garrison et al. · 2006RCTEffect of a proprietary Magnolia and Phellodendron extract on weight management — pilot randomised placebo-controlled clinical trialView study →}, mechanistically via magnolol/honokiol potentiation of the GABA-A benzodiazepine site ^{90,91Reference 90Sarrica et al. · 2018ReviewSafety and toxicology of magnolol and honokiol — reviewView study →Reference 91Qu et al. · 2012AnimalHonokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA-A receptor in mice — animal modelView study →}.

Every trial tested a two-herb proprietary blend in small, mostly female cohorts — no RCT of magnolia bark alone, and trait anxiety was unaffected.

Standardised L. cardiaca extract bound the GABA site of the rat GABA-A receptor (IC₅₀ ≈ 21 µg/mL) with little benzodiazepine-site activity, giving the traditional sedative use a mechanism ^{98Reference 98Rauwald et al. · 2015In vitroGABA-A receptor binding assays of standardized Leonurus cardiaca and Leonurus japonicus extracts and their isolated constituents — in vitroView study →}; anxiety/depression scores improved in the open-label hypertension trial ^{99Reference 99Shikov et al. · 2011Clinical trialEffect of Leonurus cardiaca oil extract in patients with arterial hypertension accompanied by anxiety and sleep disorders — clinical trial (open-label)View study →} and a small study found a motherwort tincture improved emotional state in anxious subjects, though less than melatonin ^{100Reference 100Ovanesov et al. · 2006Clinical trialEffects of melatonin and motherwort tincture on the emotional state and visual functions in anxious subjects — clinical trialView study →}.

No placebo-controlled RCT exists (a pilot for generalized anxiety, NCT06954038, is registered but not recruiting) and the compound driving GABA-A activity in this species is unidentified — leonurine, which explained the effect in L. japonicus, is absent in L. cardiaca ^{98,101,102Reference 98Rauwald et al. · 2015In vitroGABA-A receptor binding assays of standardized Leonurus cardiaca and Leonurus japonicus extracts and their isolated constituents — in vitroView study →Reference 101Kuchta et al. · 2012Leonurus japonicus, Leonurus cardiaca, Leonotis leonurus: a novel HPLC study on the occurrence and content of the guanidino derivative leonurine — analyticalView study →Reference 102ClinicalTrials.gov · 2025RCTA randomized, double-dummy, placebo-controlled pilot study of an oral supplement based on Leonurus cardiaca for mood and anxiety — registered RCT (not yet recruiting)View study →}.

A four-week RCT in healthy adolescent males found nigella seed improved mood, reduced anxiety and enhanced verbal learning, alongside an elderly-cognition RCT ^{106,107Reference 106Bin Sayeed MS et al. · 2014RCTNigella sativa L. seeds modulate mood, anxiety and cognition in healthy adolescent males — a randomized controlled trialView study →Reference 107Bin Sayeed MS et al. · 2013RCTThe effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers — a randomized controlled trialView study →}, resting on animal evidence of hippocampal protection. Both trials are small, short and in non-clinical (healthy) populations — there is no trial in diagnosed clinical anxiety, and neither result is replicated.

In saffron trials anxiety is usually a secondary outcome alongside depression. A network meta-analysis placed saffron among the better herbal anxiolytics ^{29Reference 29Zhang W et al. · 2022Meta-analysisMedicinal herbs for the treatment of anxiety: a systematic review and network meta-analysisView study →}, the affron® healthy-adult trial cut anxiety symptoms at 28 mg/day ^{121Reference 121Kell et al. · 2017RCTaffron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomised, placebo-controlled clinical trialView study →}, and a 2025 meta-analysis found it comparable to SSRIs across anxiety outcomes ^{122Reference 122Shafiee A et al. · 2025Meta-analysisEffect of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treatment of depression and anxiety: a systematic review and meta-analysis. https://pubmed.ncbi.nlm.nih.gov/38913392/View study →}. Few trials use anxiety as a primary endpoint or enrol diagnosed anxiety patients; one 2025 subclinical RCT was null ^{123Reference 123Amadieu C et al. · 2025RCTEffect of saffron extract supplementation on mood in healthy adults with subclinical symptoms of depression: a randomised, double-blind placebo-controlled studyView study →}.

Anxiety is American skullcap’s best-evidenced indication, with both a mapped mechanism and human data. An ethanol aerial-parts extract was anxiolytic in the rat elevated-plus-maze/open-field, attributed to baicalin and baicalein binding the benzodiazepine site of GABA-A, plus free GABA ^{124Reference 124Awad et al. · 2003AnimalPhytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties — animal modelView study →}; extracts also bind 5-HT7 ^{125Reference 125Gafner et al. · 2003In vitroInhibition of [3H]-LSD binding to 5-HT7 receptors by flavonoids from Scutellaria lateriflora — in vitroView study →}.

In humans, an early double-blind RCT in healthy volunteers reported anxiolytic effects ^{126Reference 126Wolfson et al. · 2003RCTAn investigation into the efficacy of Scutellaria lateriflora in healthy volunteers — a double-blind, placebo-controlled randomised trialView study →}, but a later crossover RCT (n=43, 350 mg ×3/day, 2 wk) was null on the Beck Anxiety Inventory in a minimally anxious sample while significantly reducing total mood disturbance ^{127Reference 127Brock et al. · 2014RCTAmerican Skullcap (Scutellaria lateriflora): a randomised, double-blind placebo-controlled crossover study of its effects on mood in healthy volunteersView study →}. The trials are small and enrolled healthy or minimally anxious subjects, with no diagnosed-anxiety population.

St John’s wort has no anxiety-specific trial. Two placebo-controlled RCTs of extract LI 160 in somatoform disorders found the herb beat placebo across combined symptom scales ^{128Reference 128Müller et al. · 2004RCTTreatment of somatoform disorders with StView study →} and specifically on somatic anxiety ^{129Reference 129Volz et al. · 2002RCTSt John’s wort extract (LI 160) in somatoform disorders: results of a placebo-controlled trialView study →}. That is bodily-symptom anxiety without major depression, not generalised anxiety disorder. Both trials are 6 weeks, modest, and use the same extract.

A controlled inhalation study (n=24) lowered BP and pulse while raising subjective alertness — described as “harmonisation” rather than sedation ^{135Reference 135Hongratanaworakit et al. · 2004RCTEvaluation of the harmonizing effect of ylang-ylang oil on humans after inhalation — randomized controlled trialView study →}; a pilot RCT in nursing staff reduced anxiety scores ^{136Reference 136Gnatta et al. · 2014RCTAromatherapy with ylang ylang for anxiety and self-esteem: a pilot randomized controlled trialView study →}, and single-oil RCTs reduced pre-procedural anxiety in interventional-radiology patients ^{137Reference 137Sriboonlert et al. · 2023RCTCananga odorata Aromatherapy Reduces Anxiety in Unexperienced Patients Hospitalized for Interventional Neuroradiology Procedures: A Randomized Control Trial — randomized controlled trialView study →} and produced the largest pulse drop among children in a paediatric dental trial ^{138Reference 138Patil et al. · 2025RCTYlang-ylang and lavender aromatherapy for paediatric dental anxiety — randomized controlled trialView study →}. Rodent work maps the mechanism onto serotonin/dopamine turnover and the MAPK/ERK–CREB pathway ^{139,140,141Reference 139Zhang et al. · 2016AnimalThe anxiolytic effect of essential oil of Cananga odorata exposure on mice and determination of its major active constituents — animal modelView study →Reference 140Zhang et al. · 2018AnimalCananga odorata essential oil reverses m-CPP-induced anxiety via the MAPK pathway and serotonin system in mice — animal modelView study →Reference 141Zhang et al. · 2023AnimalInhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via serotonin and dopamine metabolism — animal modelView study →}.

Direction of effect is inconsistent (one RCT found the aroma impaired memory and slowed reaction time vs peppermint ^{142Reference 142Moss et al. · 2008RCTModulation of cognitive performance and mood by aromas of peppermint and ylang-ylang — randomized controlled trialView study →}); several trials use blends and no standardised dose/grade exists.

The signature effect is a soft, sedating relaxation, best-characterised through the alkaloid nuciferine, which in NIMH PDSP screening behaves like an aripiprazole-type atypical antipsychotic (5-HT2A/2B/2C antagonist, D2 partial agonist, dopamine-transporter inhibitor) and blocked a serotonergic head-twitch in mice ^{9Reference 9Farrell et al. · 2016In vitroIn vitro and in vivo characterization of the alkaloid nuciferine — in vitro and mouseView study →}; a five-patient case series documents real sedation after use ^{10Reference 10Schimpf et al. · 2023Case reportToxicity from blue lotus (Nymphaea caerulea) after ingestion or inhalation: a case seriesView study →}, alongside ceremonial use as a relaxant ^{11,12Reference 11Emboden · 1981ReviewTranscultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual — reviewView study →Reference 12Bertol et al. · 2004ReviewNymphaea cults in ancient Egypt and the New World: a lesson in empirical pharmacology — reviewView study →}.

There is no controlled anxiety trial; the anxiolytic reputation is extrapolated from the calming profile, and the responsible alkaloid is highly variable and sometimes near-absent in authentic flowers ^{13,14Reference 13Dosoky et al. · 2023Chemical composition, market survey, and safety assessment of blue lotus (Nymphaea caerulea Savigny) extracts — analytical market surveyView study →Reference 14Poklis et al. · 2017The blue lotus flower (Nymphaea caerulea) resin used in a new type of electronic cigarette, the rebuildable dripping atomizer — analyticalView study →}.

Blue vervain’s traditional calming action has cross-species and constituent support but no human data. Crude V. officinalis extract was anxiolytic, sedative and anticonvulsant in mice (elevated-plus-maze, light–dark box, thiopental sleep, PTZ seizures) ^{15Reference 15Khan et al. · 2016AnimalAnticonvulsant, Anxiolytic, and Sedative Activities of Verbena officinalis — mouseView study →}, and a 2025 study characterised neurotropic effects of standardised V. officinalis extract in behavioural models ^{16Reference 16Koshovyi et al. · 2025AnimalVerbena officinalis LView study →}. The mechanism traces to the marker iridoids verbenalin and hastatoside — both confirmed in V. hastata — which are sleep-promoting in animals ^{17Reference 17Makino et al. · 2009AnimalHastatoside and verbenalin are sleep-promoting components in Verbena officinalis — animal modelView study →}. No human anxiety trial exists. The extract work used V. officinalis, a related species, and the iridoid work used isolated molecules, so the human use of blue vervain rests on tradition.

Rodent-only anxiolytic activity: methanol/butanol fractions of T. aphrodisiaca matched low-dose diazepam in the mouse elevated-plus-maze ^{31Reference 31Kumar et al. · 2005Anti-anxiety activity studies of various extracts of Turnera aphrodisiaca Ward — animal studyView study →}, the flavonoid marker apigenin increased exploratory behaviour across hole-board, light/dark and mirrored-chamber models ^{32,33Reference 32Kumar et al. · 2008Pharmacological evaluation of bioactive principle of Turnera aphrodisiaca — animal studyView study →Reference 33Kumar et al. · 2008Estimation of apigenin, an anxiolytic constituent, in Turnera aphrodisiacaView study →}, and an aqueous extract produced anxiolytic- and antidepressant-like effects in mice without impairing locomotion ^{34Reference 34Ana María et al. · 2019AnimalNeurobehavioral and toxicological effects of an aqueous extract of Turnera diffusa in mice — animal studyView study →}, with activity linked to GABAₐ/benzodiazepine-site modulation ^{35Reference 35Lee et al. · 2015In vitroEugenol inhibits the GABAA current in trigeminal ganglion neurons — in vitroView study →}.

The work is entirely in rodents. Apigenin content is low and mostly glycoside-bound, and no human anxiety trial of damiana exists.

Hawthorn appears in anxiety trials only inside fixed combinations: a double-blind RCT (n=264, mild-to-moderate GAD) of C. oxyacantha + Eschscholtzia californica + magnesium beat placebo on the Hamilton anxiety scale ^{22Reference 22Hanus M et al. · 2004RCTDouble-blind, randomised, placebo-controlled study of a fixed combination of Crataegus oxyacantha and Eschscholtzia californica and magnesium in mild-to-moderate anxietyView study →}, and the hypertension pilot noted an incidental anxiety trend ^{41Reference 41Walker et al. · 2002RCTPromising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertensionView study →}. Every positive result is a combination product — the effect cannot be attributed to hawthorn alone.

Mood/anxiety improvement is a frequent self-reported reason for use ^{65Reference 65Grundmann · 2017ObservationalPatterns of Kratom use and health impact in the US — Results from an online survey — observationalView study →}, but controlled support is animal-only: a hydro-alcoholic leaf extract reduced anxiety-like behaviour (open-field, elevated-plus-maze) in diabetic rats while lowering brain oxidative stress ^{66Reference 66Chen et al. · 2022AnimalAnxiolytic and Antidepressant-like Effects of Mitragyna speciosa Extract in Diabetic Rats — rat animal modelView study →}, consistent with mitragynine’s serotonergic (5-HT2A) activity ^{67Reference 67Hiranita et al. · 2022In vitroIn vitro and in vivo pharmacology of kratom — reviewView study →}.

Anxiety and irritability are also adrenergic side effects of kratom, so the direction is dose- and person-dependent. There is no human anxiety trial, and the animal model is confounded by diabetes.

Anxiety is linden’s most-replicated action, and the tested preparations match how it is used. Water and hydroethanolic Tilia inflorescence/bract extracts produce dose-dependent anxiolytic effects across the elevated-plus-maze, hole-board and open-field, several comparable to diazepam, with no toxicity at high doses ^{74,75,76Reference 74Aguirre-Hernández et al. · 2007AnimalPharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice — animal in vivo studyView study →Reference 75Pérez-Ortega et al. · 2008AnimalSedative and anxiolytic efficacy of Tilia americana var. mexicana inflorescences used traditionally by communities of the State of Michoacán, Mexico — animal in vivo studyView study →Reference 76Aguirre-Hernández et al. · 2007AnimalBioactivity-guided isolation of β-sitosterol and some fatty acids as active compounds in the anxiolytic and sedative effects of Tilia americana var. mexicana — animal in vivo studyView study →}. Mechanism maps to flavonoid (quercetin, kaempferol, tiliroside, isoquercitrin) activation of GABA-A/benzodiazepine receptors and serotonergic 5-HT1A/2A signalling ^{77,78,79,80,81Reference 77Herrera-Ruiz et al. · 2008AnimalFlavonoids from Tilia americana with anxiolytic activity in the plus-maze test — animal in vivo studyView study →Reference 78Aguirre-Hernández et al. · 2010AnimalHPLC/MS analysis and anxiolytic-like effect of quercetin and kaempferol flavonoids from Tilia americana var. mexicana — animal in vivo studyView study →Reference 79Viola et al. · 1994AnimalIsolation of pharmacologically active benzodiazepine receptor ligands from Tilia tomentosa (Tiliaceae) — animal in vivo studyView study →Reference 80Allio et al. · 2015In vitroBud extracts from Tilia tomentosa Moench inhibit hippocampal neuronal firing through GABAA and benzodiazepine receptor activation — in vitro studyView study →Reference 81Noguerón-Merino et al. · 2015AnimalInteractions of a standardized flavonoid fraction from Tilia americana with serotonergic drugs in the elevated plus maze — animal in vivo studyView study →}. The work is entirely in rodents, with no human trial ^{82Reference 82Sarris et al. · 2013ReviewPlant-based medicines for anxiety disorders, Part 1: a review of preclinical studies — reviewView study →}, and animal doses exceed what a tea delivers.

An ethnobotanically grounded study — healers across ten regions of Morelos take the herb as an infusion/tincture for nervous “culture-bound syndromes” — tested polar extracts in open-field, hole-board, plus-maze and barbiturate-potentiation models and confirmed anxiolytic/sedative effects, blocked by both a 5-HT1A antagonist (WAY-100635) and the GABA/benzodiazepine antagonist flumazenil; herniarin was isolated as a candidate active ^{97Reference 97Pérez-Ortega et al. · 2016Tagetes lucida Cav.: ethnobotany, phytochemistry and pharmacology of its tranquilizing properties — animal studyView study →}. The polar extracts match the traditional tea. The work is a single study in mice, with no dose translation and no clinical anxiety endpoint.

The anxiety signal is biphasic: POEE showed anti-stress/adaptogen-like effects in several mouse models ^{103,104Reference 103Piato et al. · 2008Effects of Marapuama in the chronic mild stress model: further indication of antidepressant properties — animal studyView study →Reference 104Piato et al. · 2010AnimalAnti-stress effects of the “tonic” Ptychopetalum olacoides (Marapuama) in mice — animal studyView study →}, but an earlier study found it produced anxiogenic-like behaviour at 30–300 mg/kg ^{105Reference 105da Silva et al. · 2002Anxiogenic properties of Ptychopetalum olacoides Benth. (Marapuama) — animal studyView study →}.

Catnip is a traditional remedy for calming and nervous tension. The human anxiety RCT commonly attributed to catnip was conducted on Nepeta menthoides, a different species, not N. cataria ^{24Reference 24Firoozabadi A et al. · 2016RCTEfficacy of Nepeta menthoides Boiss and Buhse freeze-dried aqueous extract on anxiety of patients with depression: a double-blind randomized controlled clinical trial — [human RCT (different species)]View study →}.

Catnip’s own CNS data are contradictory rodent studies ^{25,26Reference 25Harney JW et al. · 1978AnimalBehavioral and toxicological studies of cyclopentanoid monoterpenes from Nepeta cataria — [animal in vivo]View study →Reference 26Massoco CO et al. · 1995AnimalBehavioral effects of acute and long-term administration of catnip (Nepeta cataria) in mice — [animal in vivo]View study →}, and its active iridoid does not activate human TRPA1 ^{27Reference 27Melo N et al. · 2021In vitroThe irritant receptor TRPA1 mediates the mosquito repellent effect of catnip — [in vitro / in vivo mechanism]View study →}, consistent with its mildness in people.

Marjoram is used traditionally as a mild calming aromatic. There is no anxiety trial.

In TCM reishi is a shen tonic that calms the nerves and eases anxiety without being directly sedative ^{117,118Reference 117Rogers · 2011The fungal pharmacy: The complete guide to medicinal mushrooms and lichens of North America [Adobe Digital Editions version]Reference 118Hempen et al. · 2009A Materia Medica for Chinese Medicine: Plants, Minerals, and Animal Products. (Pg}. There is no anxiety-specific trial.

The closest research is a neurasthenia RCT, in which Ganopoly reduced fatigue and improved wellbeing in 132 patients ^{119Reference 119Tang W et al. · 2005RCTA randomised, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia — randomised controlled trialView study →}, and lucidone D’s sedative activity in mice ^{120Reference 120Feng X · 2019In vitroAnti-inflammatory, anti-nociceptive and sedative-hypnotic activities of lucidone D extracted from Ganoderma lucidum — in vitro and mouse studyView study →}; neither measured anxiety.

Rose has a long traditional and aromatherapeutic use for soothing and lifting the spirits. There is no clinical anxiety trial of the herb itself.

Valerian’s mechanism is well mapped: valerenic acid + valerenol potentiate GABA-A at a β2/β3-dependent site, anxiolytic in mice and abolished in β3(N265M) point-mutant mice — direct in-vivo causal evidence ^{130,131Reference 130Khom S et al. · 2007Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificityView study →Reference 131Benke D et al. · 2009AnimalGABA-A receptors as in vivo substrate for the anxiolytic action of valerenic acidView study →}, with the effect tracking valerenic acid and cancelled by acetoxyvalerenic acid ^{132Reference 132Becker A et al. · 2014The anxiolytic effects of a Valerian extract is based on valerenic acidView study →}.

The human trials are weaker: Cochrane found only one eligible trial and judged the evidence insufficient ^{133Reference 133Miyasaka LS et al. · 2006Valerian for anxiety disordersView study →}, a network meta-analysis did not find valerian effective ^{29Reference 29Zhang W et al. · 2022Meta-analysisMedicinal herbs for the treatment of anxiety: a systematic review and network meta-analysisView study →}, and a GAD pilot was negative ^{134Reference 134Andreatini R et al. · 2002RCTEffect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot studyView study →}.

Wood betony is a traditional Western nervine for nervous headache and tension. There is no anxiety trial.