Top 10 Evidence-Based Recommendations

Standardized linalool-rich lavender oil modulates glutamate and GABA signaling and reduces limbic hyperactivity—lowering psychic and somatic anxiety without sedation.^[1][2]

Five RCTs meta-analyzed show Silexan 80 mg/day beats placebo on Hamilton Anxiety (HAMA). In a 539-person head-to-head, 80–160 mg/day outperformed placebo and was comparable to paroxetine on some analyses with fewer AEs.^[1][2] Best evidence is for anxiety, with ancillary mood benefits.

EPA-derived resolvins dampen neuroinflammation and may normalize monoamine signaling; DHA-heavy formulas did not show the same mood benefit.^[3][4][5]

Meta-analyses show small-to-moderate benefit for depression, driven by EPA-major or pure EPA at ≤1 g/day; DHA-focused products underperform. Recent umbrella/meta-analyses confirm benefit mainly as add-on and in mild–moderate cases.^[3][4][5]

Restores inhibitory tone via NMDA antagonism and GABA support; low magnesium states heighten stress circuitry and HPA activity.^[6][10]

An open-label randomized crossover trial (n=112) found 248 mg/day improved PHQ-9 by ~6 points within 2 weeks; a 2023 meta-analysis of RCTs in depressive disorder showed significant symptom reduction (SMD ~ −0.92).^{[6][7][8][10]}

Crocin/safranal modulate serotonin, dopamine, and anti-inflammatory pathways; may improve sleep quality and anxiety alongside mood.^[11][14]

Meta-analyses show saffron outperforms placebo on self-rated scales and can equal SSRIs in mild–moderate depression; umbrella review notes benefits mainly on BDI with mixed clinician-rated outcomes.^[11][13][14]

Increases alpha brain waves and supports GABA, dopamine, and serotonin—promoting a relaxed yet alert state.^[9]

Systematic review of RCTs suggests 200–400 mg/day reduces stress/anxiety in stressful conditions; low risk and helpful as an add-on for anxious depression.^[9]

Reduces HPA-axis hyperactivity and lowers cortisol; may enhance GABAergic signaling.^[15][16]

Recent meta-analyses of RCTs show significant reductions in anxiety/stress (PSS, HAMA) and cortisol, with low–moderate certainty.^[15][16]

Gut–brain axis: microbial metabolites (SCFAs), vagal signaling, tryptophan–serotonin pathway, and cytokine modulation reduce neuroinflammation.^[17]

2025 meta-analysis (n≈3179) finds small but significant reductions in depression and anxiety, with greater benefit in mild symptoms.^[17]

Donates methyl groups for monoamine synthesis (via BH4), supporting serotonin, dopamine, and norepinephrine production.^[18][22]

2023 meta-analysis of 23 RCTs: SAMe better than placebo (SMD −0.58) and similar to antidepressants; 2024 update shows mixed results overall but comparable to SSRIs/TCAs with good tolerability.^[18][21]

Downregulates NF-κB/oxidative pathways and may increase BDNF; inflammation-linked depression often responds.^[23][24][25]

Meta-analyses show small-to-moderate antidepressant effects and improved response rates; evidence quality variable but safety good.^[23][26][25]

Modulates monoamines and HPA stress response; may reduce fatigue and improve resilience.^[12]

RCTs suggest benefit in mild–moderate depression and as add-on to sertraline; more data needed but promising with low side effects.^[12]