Ranked by evidence within the category
Stress and mood supplements: what the evidence says
This category covers 36 supplements for stress, anxiety and mood: 1 is rated strong, 7 moderate and 28 limited. St John's Wort stands alone at the top, working about as well as standard antidepressants for mild-to-moderate depression, while Silexan lavender extract and standardised chamomile have the better-replicated anxiety data among the calming herbs. Saffron and ashwagandha are promising but rest on small trials, and most of the remaining list, from rhodiola and 5-HTP to CBD and adaptogen blends, has limited evidence.
Evidence last reviewed: September 2026
Strong evidence (1)
St John's Wort is the rare herbal supplement with genuinely strong efficacy data — it works about as well as standard antidepressants for mild-to-moderate depression, with better tolerability.
Moderate evidence (7)
An adaptogenic herb from Ayurvedic medicine.
SAM-e has more RCT support than most mood supplements, but Cochrane found the evidence low quality and inconclusive; it is expensive, unstable, and carries a genuine risk of triggering mania in people with bipolar disorder.
Standardised chamomile extract has real, replicated RCT support for reducing generalised anxiety symptoms over 8 weeks — one of the better-evidenced calming herbs.
Silexan, a specific oral lavender oil preparation, has the strongest clinical dataset of any calming herbal — multiple large placebo-controlled RCTs showing meaningful anxiety reduction without sedation or dependence.
Older meta-analytic data show kava beats placebo for anxiety, but the largest and best-conducted modern trial was flatly negative — and the drug carries a genuine, regulator-recognised hepatotoxicity signal.
Saffron has repeatedly beaten placebo and matched fluoxetine for mild-to-moderate depression in randomized trials, and the effect sizes are large enough to be suspicious.
High-dose B vitamin complexes aimed at perceived stress.
Limited evidence (28)
L-methylfolate is the bioactive form of folate, heavily marketed to people with MTHFR variants and treatment-resistant depression.
Despite decades of popularity as a natural antidepressant, 5-HTP's clinical evidence is thin and dated: systematic reviews found almost no trials of acceptable quality, and the drug-interaction risk is real.
L-ornithine has a coherent biochemical story around ammonia clearance and a couple of small positive Japanese trials for fatigue and sleep, but the total human evidence amounts to a few dozen participants.
Rhodiola is one of the better-studied adaptogens, but that is a low bar: the fatigue trials are small and mostly at high risk of bias, and the one rigorous depression trial found it no better than placebo.
Sold as an adaptogen for stamina and stress resistance, but the best controlled trial found no overall benefit for chronic fatigue.
Small trials consistently report benefits for stress and blood glucose, but that consistency is itself a red flag: literally every published human study is favourable, most are small, short and industry-linked, and none are large or independently replicated.
Genuinely interesting pharmacology - kanna's alkaloids inhibit serotonin reuptake and PDE4 - but the entire human evidence base is three tiny studies totalling under 80 people.
Magnolia bark's active compounds honokiol and magnolol have genuinely interesting GABA-A activity in animals, but the human evidence is a couple of tiny industry-funded pilot studies on a Magnolia-Phellodendron blend.
CBD is a genuinely effective prescription anticonvulsant at 10-20 mg/kg/day — but the evidence for the reasons people actually buy it, anxiety, sleep and pain, is thin and inconsistent, and typical over-the-counter doses of 10-50 mg are far below anything ever shown to work.
There are no randomised controlled trials of lithium orotate for mood, cognition or anything else — the entire marketing case rests on extrapolation from prescription lithium carbonate and from ecological studies of lithium in drinking water.
Isoflavone-standardized kudzu extract has repeatedly reduced how much alcohol heavy drinkers consume in small trials - but nearly all of them come from one research group.
Phenylethylamine is a trace amine marketed as an instant mood and focus booster, but oral PEA is destroyed within minutes by monoamine oxidase B before it reaches the brain.
L-phenylalanine is the essential amino acid precursor to tyrosine, dopamine and noradrenaline, sold for mood, focus and appetite control.
DLPA is a 50/50 racemic mix of L-phenylalanine (a dietary amino acid) and D-phenylalanine (a synthetic isomer claimed to block enkephalin breakdown and relieve chronic pain).
Adrenal fatigue is not a recognized medical condition, and a systematic review of 58 studies concluded it does not exist.
A marketing category built on a real research field: probiotics claimed to improve mood, anxiety or stress via the gut-brain axis.
Bach flower remedies, including Rescue Remedy, have been tested in placebo-controlled trials for anxiety and pain, and systematic reviews conclude they perform no better than placebo.
Phenibut is a prescription central nervous system depressant in several countries that is sold online in the US as a 'dietary supplement' — which it is not.
A root used as the chief herb in classical Chinese formulas for stress and low mood.
Sold almost exclusively paired with magnolia bark in a proprietary extract marketed for cortisol and stress.
A traditional European herb for palpitations and nervous tension.
A non-intoxicating minor cannabinoid promoted for anxiety and inflammation.
Multi-herb formulas built around ashwagandha, rhodiola, eleuthero and similar plants.
Combination products mixing herbs, amino acids and B vitamins for low mood.
Herbal blends sold to blunt nicotine craving.
A traditional herb whose alkaloid lobeline resembles nicotine and was long promoted for quitting smoking.
An aromatic culinary herb tested mostly as an aroma rather than a supplement.
A classical Chinese formula prescribed for stress-related complaints.
Comparison guides for this category
Folic acid, L-methylfolate or folinic acid?
Basic, methylated or 'stress' B-complex?
Plain L-ornithine or ornithine alpha-ketoglutarate?
Plain L-phenylalanine or the DL mix sold for pain?
The dietary amino acid or the step-closer precursor?
Ashwagandha, rhodiola or L-theanine?
Goals these supplements are ranked for
Which anxiety and stress supplements actually have trials behind them, ranked by strength of evidence — plus the popular ones worth…
An evidence-ranked guide to supplements for low mood and mild depression: what has trial support, the interaction risks, and what to skip.
What actually helps you fall asleep and stay asleep, ranked by strength of evidence — plus the popular sleep supplements that do not hold…
Our verdict
Low mood deserves a doctor first; if you do try something, St John's Wort has the strongest evidence but also the most dangerous drug interactions, including contraceptive failure, so check every medication you take. Be sceptical of kava, whose best modern trial was negative and which carries a liver-toxicity signal, and of adrenal, adaptogen and mood-support formulas, which sit in the limited tier.