Natural supplements for anxiety and depression have gained significant attention as people seek alternatives or adjuncts to conventional treatments. Ingredients like saffron, SAM-e, St. John’s Wort, and 5-HTP have been studied in clinical trials showing meaningful effects on mood, stress response, and emotional well-being. The best options target neurotransmitter production, reduce cortisol, or support the body’s natural serotonin and dopamine pathways.
Quick Comparison
Product
Key Ingredient
Form
Best For
Rating
Effective Nutra Saffron Gummies
Saffron + Vitamin D2
Gummies
Best Overall
9.5/10
SAM-e 400mg
SAM-e (S-Adenosyl Methionine)
Tablets
Best Clinically Studied
9.3/10
St. John’s Wort
St. John’s Wort Extract
Capsules
Best for Mild-Moderate Depression
9.2/10
Genius Joy
SAM-e + Rhodiola + Red Panax Ginseng
Capsules
Best Multi-Action Formula
9.1/10
Luma Nutrition Saffron
Saffron Extract 88.5mg
Capsules
Best Saffron Capsule
9.0/10
Bioactive SAM-e 750mg
SAM-e (Biologically Active S,S Form)
Tablets
Best High-Potency SAM-e
8.9/10
SAM-e 500mg
SAM-e 500mg
Tablets
Best Value SAM-e
8.8/10
1. Effective Nutra Saffron Gummies – Best Overall
Effective Nutra Saffron Gummies | Sugar-Free Supplement with Vitamin D2, Passion Flower, St. John’s Wort & GABA | Positive Mood, Digestion, Energy | Natural Berry Flavor, Made in USA (90 Count)
#1 ULTIMATE SAFFRON GUMMY: Not a fan of swallowing large capsules? Our sugar free saffron gummies taste good & go down easy. 90 Gummies in a bottle for the best value out there!*
GET ALL THE BENEFITS: Our saffron supplement is packed with a 5-in-1 blend that may promote positive mood and attitude, digestion, physical fitness, increase in energy and focus, stress relief, heart health and brain function.*
SUPPORTS HEALTHY MOOD: Saffron extract has a long history of traditional use for supporting a healthy mood and promoting emotional balance. A great way to maintain a positive attitude and mood all day long!*
HEALTHY & DELICIOUS: Yes, we did it! At Effective Nutra we want to provide a healthy and enjoyable experience. Our saffron gummies are naturally berry flavored. With no artificial colors or flavors, you can be sure you’re getting the most nourishing health gummies out there!*
EFFECTIVE NUTRA’S SEAL OF EXCELLENCE: QUALITY YOU CAN TRUST: Our supplements are Vegan, Gluten-Free, Non-GMO, Third Party Tested, GMP Certified and proudly Made in USA with Globally Sourced Ingredients. That’s the Effective Nutra seal of excellence!*
These sugar-free saffron gummies combine clinically studied saffron extract with vitamin D2 and passionflower for a comprehensive mood support formula in a convenient, great-tasting format.
Each serving delivers a standardized saffron extract alongside vitamin D2 and passionflower to support emotional balance, reduce stress, and promote calm. Saffron is one of the most well-researched natural mood ingredients, with multiple randomized controlled trials demonstrating effects comparable to conventional treatments for mild to moderate mood challenges. The sugar-free gummy format makes daily compliance easy and enjoyable. Manufactured in a GMP-certified facility, this formula avoids artificial colors and unnecessary fillers.
Pros:
Clinically studied saffron extract for mood support
Sugar-free gummy format with great taste
Added vitamin D2 and passionflower for comprehensive support
Cons:
Gummies may deliver lower extract concentrations than capsules
Contains sugar alcohols for sweetening
Best for: Those seeking an enjoyable, multi-ingredient mood supplement backed by clinical research on saffron
2. SAM-e 400mg – Best Clinically Studied
SAM-E Supplement 400mg | Easy Absorption S-Adenosyl-L-Methionine SAM-e 400mg for Bone and Mood Support Supplement | Made in The USA Non-GMO and Gluten Free (90 Day Supply)
What’s Inside – SAM-e – short for S-adenosylmethionine – is a naturally occurring compound involved in many essential processes particularly among major brain transmitters
One Supplement Many Benefits – Our high potency SAM e supplement offers a variety of benefits ranging to promoting a better mood
Made with Love – We make it our mission to provide accessible supplements to all which is why our SAM-e is made without artificial flavors and colors, preservatives, corn, dairy, sodium, or soy
Premium Quality Solid Support – NasaBeahava is committed to making the highest quality supplements affordable for all consumers
Want More Supplements – We’re proud to present a wide range of premium quality supplements including CoQ10, Phytoceramides, Resveratrol, Pterostilbene and more Just visit the NasaBeahava Store
SAM-e (S-Adenosyl-L-Methionine) is one of the most extensively researched natural compounds for mood support, with decades of clinical evidence backing its effectiveness.
This easy-absorption formula provides 400mg of SAM-e per tablet, a dosage within the range shown effective in clinical trials for mood support. SAM-e plays a critical role in methylation reactions throughout the body, directly influencing neurotransmitter production including serotonin, dopamine, and norepinephrine. Over 40 clinical studies have evaluated SAM-e for mood disorders, with meta-analyses confirming significant benefits compared to placebo. The enteric-coated tablets protect the active ingredient from stomach acid degradation for improved bioavailability. For those also experiencing sleep disruptions related to mood, a magnesium for sleep supplement can provide complementary support.
Pros:
Backed by over 40 clinical studies for mood support
400mg dosage in the effective clinical range
Supports mood through multiple neurotransmitter pathways
Cons:
Should not be combined with SSRIs or MAOIs without medical guidance
Best taken on an empty stomach, which may cause mild nausea initially
Best for: Those seeking the most clinically validated natural supplement for mood support
3. St. John’s Wort – Best for Mild to Moderate Depression
St John’s Wort Capsules – Powerful & Potent Saint John’s Wort Extract & Whole Herb Complex Standardized to 900mcg Hypericin for Balancing Daily Mood Support – Vegan Non-GMO & Lab Verified (120 Caps)
Turn To St. John’s Wort: For centuries, people have turned to St. John’s Wort (commonly misspelled wart) for all the benefits it can provide. Now we know it contains a natural active chemical called Hypericin – and Healths Harmony’s high-potency formula provides 900mcg of Hypericin in every serving.
Quality And Quantity: We keep servings simple with one capsule per serving and 120 capsules per bottle. There’s no nasty tincture to taste and no gritty pills, just potent extract standardized to 0.3% Hypericin for optimal support.
Manufactured To Immaculate Standards: We manufacture these non-GMO powder capsules in a GMP-certified facility right here in the USA using globally sourced ingredients. Our precision formulation means you can be sure that what’s listed on the bottle is what you actually get – every single time – nothing but pure St. John’s Wort and something to hold the capsule together.
Order Today: Try a full bottle of our St. John’s Wort and see for yourself the difference this natural mood helper can make to your day; click add to cart today!
St. John’s Wort is the most studied herbal remedy for mood support, with clinical evidence showing efficacy comparable to standard treatments for mild to moderate depressive symptoms.
This potent formula combines St. John’s Wort extract with whole herb for a full-spectrum approach. The extract is standardized to hypericin and hyperforin, the active compounds responsible for the herb’s mood-supporting properties. St. John’s Wort works by inhibiting the reuptake of serotonin, dopamine, and norepinephrine, similar to conventional approaches but through a natural mechanism. A comprehensive Cochrane Review analyzing 29 clinical trials concluded that St. John’s Wort extracts are superior to placebo and comparable to standard treatments for mild to moderate depression.
Pros:
One of the most extensively studied herbal mood supplements
Standardized extract ensures consistent potency
Affordable price point for long-term use
Cons:
Interacts with numerous medications including birth control, blood thinners, and antidepressants
Can cause photosensitivity in some users
Best for: Those with mild to moderate mood challenges who want a well-researched herbal option (after checking for medication interactions)
4. Genius Joy – Best Multi-Action Formula
Genius Joy, Nootropic Mood Enhancer Supplement – Support Cognitive Health, Enhance Mood & Neural Function with Brain Boosting L-Theanine, Panax Ginseng & SAM-e – Organic, Non-GMO, & Gluten-Free
Amp Up the Joy in Your Life*: Genius Joy by the Genius Brand is a natural mood-boosting supplement formulated with high-quality ingredients including SAMe, Panax Ginseng, and L-Theanine. Genius Joy is non-GMO, organic, gluten free, and made in the USA. Serving size 4 vegetarian capsules, 25 servings per container.
Enhance Mood & Neural Function*: Genius Joy’s hand-picked blend of nootropics, adaptogens, and natural energy boosters promote a natural sense of well-being. SAMe has been shown to support and enhance mood and neural function, and 5-HTP increases serotonin levels
Support Cognitive Health: L-Theanine, N-Acetyl-L-Tyrosine, and Rhodiola support calm, alertness, and mental focus. Red Panax Ginseng may support focus, concentration, memory, and energy.*
Genius Joy takes a multi-pathway approach to mood support, combining SAM-e with rhodiola, red panax ginseng, and other nootropic ingredients for both emotional balance and cognitive enhancement.
This nootropic mood enhancer stacks SAM-e with adaptogenic herbs and cognitive-supporting nutrients to target mood from multiple angles. Rhodiola rosea helps the body adapt to stress and reduce cortisol, while red panax ginseng supports energy and mental clarity that can diminish during depressive episodes. The formula is designed by The Genius Brand, known for their evidence-based approach to supplement formulation. Unlike single-ingredient mood supplements, Genius Joy addresses the interconnection between mood, energy, and cognitive function that many people experience. If focus is also a concern, see our roundup of focus supplements for ADHD.
Pros:
Multi-pathway approach targets mood, stress, and cognition simultaneously
Includes adaptogens for stress resilience
Well-formulated by a reputable nootropic brand
Cons:
Contains SAM-e, so same medication interaction warnings apply
Higher capsule count per serving (3 capsules)
Best for: Those who want mood support alongside cognitive enhancement and stress adaptation
5. Luma Nutrition Saffron Extract – Best Saffron Capsule
Luma Nutrition Saffron Extract Capsules – Premium Saffron Supplements – 88.50 mg Pure Saffron Pills – Mood Support – Eye Support – Made in The USA – 60 Capsules
Potent & Effective – Elevate Health Naturally: Unleash the power of our natural saffron extract, a top-tier supplement for improved macular eye health, mood enhancer, brain support and energy support. Elevate your wellness journey with proven efficacy.
Many Health Benefits: Our optimized saffron powder is used by many as an effective eye supplement for both men and women. It may also help support overall metabolic function for healthy weight management.
Mood Boosting Marvel – Elevate Positivity: Transform your mood with Luma Nutrition saffron pills, a renowned mood support supplement. Embrace a natural mood boosting that promotes serotonin and positive energy support without the added sugar of Saffron gummies.
Easy 1-Month Supply: Create a solid daily routine with Luma’s 30-day supply of premium saffron supplements for kids and adults. Makes the perfect monthly subscription! Always stay in stock and save money at the same time!
USA-Made Excellence – Veteran Owned: Trust Luma Nutrition’s saffron capsules, crafted in GMP certified US facilities. We’re family-owned, committed to quality, and here to support your well-being journey.
This premium saffron supplement delivers 88.50mg of pure saffron extract per capsule, providing a clinically meaningful dose of the mood-supporting spice in a simple daily capsule.
Saffron extract has emerged as one of the most promising natural ingredients for mood support, with clinical studies showing effects on both anxious and depressive symptoms. The active compounds safranal and crocin influence serotonin metabolism and provide antioxidant protection for brain cells. This Luma Nutrition formula delivers a standardized extract at a dose consistent with successful clinical trials. The vegetarian capsules are free from common allergens and manufactured in a GMP-certified facility in the USA.
Pros:
Clinically relevant saffron dose at 88.50mg
Simple one-capsule daily serving
Well-tolerated with minimal side effects
Cons:
Single-ingredient formula may need pairing with other mood supports
Results typically take 4-6 weeks to manifest
Best for: Those who want a targeted saffron supplement in capsule form for daily mood support
6. Bioactive SAM-e 750mg – Best High-Potency SAM-e
Bioactive SAM-e 750mg – High Strength SAM-e Supplement with Biologically Active S,S Form for Liver and Mood Support – Vegan Non-GMO Preservative Free – Made in The US (30 Capsules)
Precision Dosage: Take one capsule daily of our 750mg SAMe supplements designed to provide enhanced comfort physically and emotionally as this nutrient offers both mood and brain support
Active Form: We formulated our SAM e supplement 750mg with s-adensosyl l-methionine disulfate tosylate which offers enhanced bioavailability so you get more of the SAM-E benefits out of each dose
The Clear Difference: At Clear Formulas we believe transparency and trust are essential which is why our product is made in a cGMP American facility according to strict regulatory guidelines
Made for All in Mind: We stand by our name and our formula is made without many common allergens and additives including dairy, gluten, salt, soy, wheat or artificial preservatives
The Choice is Clear: We believe health doesn’t have to be hard – We make it simple with carefully designed supplements to support your needs. Whatever your age and lifestyle we’ve got you covered
For those who need a higher SAM-e dose, this 750mg formula delivers the biologically active S,S form for maximum efficacy and faster results.
This high-strength SAM-e supplement provides 750mg per tablet of the biologically active S,S form, which is the specific isomer shown to be effective in clinical research. Many cheaper SAM-e supplements contain a mix of active and inactive forms, diluting the effective dose. By providing only the S,S form, this formula ensures the full 750mg is bioavailable. The higher potency is suitable for those who have found lower doses insufficient or who want to reach therapeutic levels more efficiently. Enteric coating protects the SAM-e from degradation in the stomach.
Pros:
750mg of biologically active S,S form per tablet
Higher potency than standard 200-400mg products
Enteric coated for stability and absorption
Cons:
Higher dose may not be necessary for everyone
Premium pricing for the high-potency format
Best for: Those who need a higher SAM-e dose or haven’t responded adequately to standard-potency products
7. SAM-e 500mg – Best Value SAM-e
SAM-E Supplement 500mg | Easy Absorption S-Adenosyl-L-Methionine SAM-e 500mg for Bone and Mood Support Supplement | Made in The USA Non-GMO and Gluten Free (90 Day Supply)
What’s Inside – SAM-e – short for S-adenosylmethionine – is a naturally occurring compound involved in many essential processes particularly among major brain transmitters
One Supplement Many Benefits – Our high potency SAM e supplement offers a variety of benefits promoting a better mood
Made with Love – We make it our mission to provide accessible supplements to all which is why our SAM-e is made without artificial flavors and colors, preservatives, corn, dairy, sodium, or soy
Premium Quality Solid Support – NasaBeahava is committed to making the highest quality supplements affordable for all consumers
Want More Supplements – We’re proud to present a wide range of premium quality supplements including CoQ10, Phytoceramides, Resveratrol, Pterostilbene and more Just visit the NasaBeahava Store
This 500mg SAM-e supplement hits the sweet spot between dosage and value, providing a mid-range potency at an accessible price point.
Each easy-absorption tablet delivers 500mg of SAM-e for mood, joint, and liver health support. The 500mg dose falls within the range commonly used in clinical studies (400-800mg daily) and gives users flexibility to adjust their intake. SAM-e is unique among mood supplements because it also supports joint comfort and liver function through its role in methylation and glutathione production. This makes it particularly valuable for those dealing with mood challenges alongside other health concerns.
Pros:
Versatile 500mg dose suitable for most users
Supports mood, joints, and liver health simultaneously
Good value per milligram of SAM-e
Cons:
Must be stored properly to maintain potency (SAM-e is sensitive to heat and moisture)
Best taken on empty stomach, which some find inconvenient
Best for: Those looking for a mid-range SAM-e dose with multi-system benefits at a reasonable price
8. 1500mg SAM-e Supplement – Best Maximum Strength
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For users who want the highest available daily SAM-e dose in a single product, this 1500mg per serving formula delivers maximum therapeutic support.
This high-strength SAM-e supplement provides 1500mg per serving for those who need the upper end of the therapeutic range. Higher SAM-e doses have been used in clinical settings with positive outcomes for more persistent mood challenges. The capsule format is easy to take and the formula includes no unnecessary fillers or additives. While higher doses of SAM-e should be approached thoughtfully, this product provides the potency that some users need to achieve meaningful results. For a calming complement, many users also benefit from L-theanine for anxiety.
Pros:
Maximum strength 1500mg per serving
Provides the upper therapeutic range in a single product
Clean formula without unnecessary additives
Cons:
High dose should be used under professional guidance
May cause mild GI discomfort at higher doses initially
Best for: Experienced SAM-e users who need maximum potency for persistent mood challenges
How to Choose the Best Supplement for Anxiety and Depression
Start by identifying whether your primary concern is anxiety, depression, or both. Saffron extract and SAM-e show benefits for both anxiety and depressive symptoms. St. John’s Wort has the strongest evidence specifically for mild to moderate depression but may be less effective for anxiety-dominant presentations. L-theanine, magnesium, and ashwagandha tend to be more effective for anxiety-dominant concerns.
Dosage matters significantly with mood supplements. SAM-e is typically studied at 400-1600mg daily, saffron at 30-100mg, and St. John’s Wort at 300-900mg of standardized extract. Starting at the lower end and gradually increasing allows you to find the minimum effective dose while minimizing potential side effects.
Drug interactions are a critical consideration, especially with St. John’s Wort and SAM-e. St. John’s Wort interacts with dozens of medications by inducing liver enzymes that metabolize drugs faster. SAM-e should not be combined with SSRIs, SNRIs, or MAOIs due to the risk of serotonin syndrome. Always review potential interactions with a healthcare provider before starting mood supplements.
Look for standardized extracts that guarantee specific levels of active compounds. For St. John’s Wort, this means standardization to hypericin (0.3%) and hyperforin (1-6%). For saffron, look for standardization to safranal and crocin. Third-party testing and GMP certification provide additional quality assurance.
Frequently Asked Questions
What is the best natural supplement for anxiety and depression?
SAM-e and saffron extract have the broadest clinical evidence for supporting both anxiety and depressive symptoms. SAM-e has been studied in over 40 clinical trials and works by supporting neurotransmitter production. Saffron extract has shown effects comparable to standard treatments in multiple controlled trials. The best choice depends on individual needs, medication use, and whether anxiety or depression is the primary concern.
Can supplements replace antidepressant medications?
Supplements should not be used as a direct replacement for prescribed medications without professional guidance. Some supplements like SAM-e and St. John’s Wort have clinical evidence supporting their use for mild to moderate symptoms, but severe depression typically requires professional treatment. Supplements can be valuable as complementary support or for those with milder symptoms who prefer natural approaches.
How long do mood supplements take to work?
Most mood supplements require 2-6 weeks of consistent use before noticeable effects. SAM-e may show initial benefits within 1-2 weeks, which is faster than many conventional options. Saffron typically requires 4-6 weeks for full effects. St. John’s Wort usually takes 4-6 weeks to reach peak effectiveness. Patience and consistency are key with natural mood support.
Can I take SAM-e with other supplements?
SAM-e can generally be safely combined with most vitamins and minerals, including B vitamins, magnesium, and omega-3s. In fact, B vitamins (especially B6, B9, and B12) support SAM-e’s methylation activity and are often recommended alongside it. However, SAM-e should not be combined with St. John’s Wort, 5-HTP, or any serotonergic supplements or medications without professional guidance due to the risk of excessive serotonin levels.
Are there side effects of mood support supplements?
SAM-e may cause mild GI discomfort, anxiety, or insomnia at higher doses—starting low and increasing gradually helps. St. John’s Wort can cause photosensitivity, dry mouth, and digestive upset. Saffron is generally well-tolerated, with rare side effects at recommended doses. The most important safety consideration is medication interactions, particularly with St. John’s Wort, which affects the metabolism of numerous prescription drugs.
Is saffron really effective for mood?
Yes, multiple randomized, double-blind, placebo-controlled trials have demonstrated that saffron extract (typically 30-100mg daily) significantly improves mood symptoms compared to placebo. Several studies have even found saffron comparable in effectiveness to standard treatments. The active compounds safranal and crocin appear to influence serotonin metabolism in the brain, providing a natural mechanism for mood support.