Top 10 Evidence-Based Recommendations

Standardized linalool/linalyl acetate modulate glutamate and GABA signaling and dampen limbic hyperarousal; human data show robust Hamilton Anxiety (HAMA) drops. ^{[1][2][3][4][5]}

Across 5 RCTs, 80–160 mg/day reduced HAMA vs placebo; 160 mg showed responder rates >60%. In a 539-person head-to-head, Silexan 160 mg outperformed placebo and was comparable to paroxetine on several endpoints with fewer AEs. Network/meta-analyses confirm benefit. ^[1][2][4][5]

Increases alpha brain waves and balances excitatory neurotransmission, reducing cortisol response to stressors without impairing performance. ^[6][7][8][9]

Randomized crossover studies show a single 200 mg dose lowers stress markers (cortisol/EEG) during acute stress; 200–400 mg/day for 4 weeks improves trait anxiety and sleep quality vs placebo. ^[6][7][8][9]

Modulates HPA-axis and GABAergic signaling; human trials show decreases in PSS, HAM-A, and serum cortisol. ^[10][11][12]

Meta-analyses of RCTs (n≈9–12 trials) show meaningful reductions in PSS (MD ≈ −4.7), HAM-A, and cortisol vs placebo; most effective around 300–600 mg/day; certainty of evidence low–moderate. ^[10][11][12]

Restores Mg-dependent GABA and NMDA balance; deficiency increases stress reactivity. Organic salts (citrate/glycinate) absorb better than oxide. ^{[17][18][19][20]}

Systematic review suggests benefit for anxiety in vulnerable groups; newer RCTs support mood benefits. Bioavailability studies consistently show citrate/glycinate > oxide (oxide often ≈ placebo). ^{[17][18][19][20]}

Inhibits GABA-transaminase and modulates cholinergic signaling, producing anxiolysis and improved sleep quality. ^{[21][22][23][24]}

Double-blind crossover trials show reduced stress reactivity and increased calm within 1–3 h; small clinical studies show improvements in anxiety/sleep over ~2 weeks. Meta-analysis supports benefit with minimal side effects. ^[21][22][23]

Crocins and safranal modulate serotonin and increase evening melatonin; RCTs show improved sleep quality and lower anxiety ratings. ^[25][26][27]

Meta-analysis shows reductions in anxiety (BAI) with mixed results on HAMA; multiple RCTs in poor sleepers show clinically meaningful ISI/quality improvements within 1–4 weeks. Well-tolerated. ^[25][26][27]

Anti-inflammatory and neuroplastic effects; meta-analysis shows modest anxiolytic effect, stronger in clinical populations and at ≥2 g/day. ^[28]

19-trial meta-analysis (n=2,240) found reduced anxiety symptoms vs control; effects larger at ≥2,000 mg/day. ^[28]

Adaptogen that normalizes stress-induced HPA and reduces cortisol awakening response, improving attention under fatigue. ^[29]

Randomized trial in stress-related fatigue/burnout showed improved burnout scores and attention vs placebo, with altered cortisol response. ^[29]

GABA_A modulation and reduced excitatory neurotransmission; multiple trials show HAM-A reductions vs placebo. ^[30][31]

Cochrane review: small–moderate benefit vs placebo; NCCIH notes liver-injury risk despite short-term RCTs showing normal LFTs. Use only short-term and from reputable, root-only water extracts. ^[30][31]

Apigenin-rich extract binds benzodiazepine sites on GABA_A receptors, promoting anxiolysis with minimal sedation. ^[32]

Placebo-controlled trial in mild–moderate GAD showed greater HAM-A reduction vs placebo; long-term data suggest symptom reduction with excellent safety. ^[32][33]