Saffron is the dried stigma of the Crocus sativus plant native to the Middle East. And is the world’s most expensive culinary spice largely due to the way it must be grown and harvested (by hand).
Today, Saffron is used to help manage appetite, for energy and stamina, anxiety, and is a very effective antidepressant.
Recent studies show Saffron as effective as some popular prescription antidepressants. And can even help alleviate the sexual dysfunction caused by these drugs.
I first became aware of Saffron when researching this ingredient included in Performance Lab Vision.
And then noticed in the last year that it was appearing on shelves as a standalone supplement in the ‘brain health’ section of local vitamin and health food shops.
Here we’ll explore how Saffron benefits your brain.
- Anxiety & depression: Saffron extracts (crocin & safranal) inhibit the uptake of dopamine and norepinephrine in the brain which helps improve mood.
- Alzheimer’s & dementia: Saffron inhibits the deposit of amyloid-β which is associated with the progression of Alzheimer’s disease. Saffron also inhibits the breakdown of acetylcholine (acetylcholinesterase) just like the current medication (donepezil) approved to treat Alzheimer’s.
- Neuroprotectant: Crocin and safranal which are unique carotenoids in Saffron make it a potent antioxidant. Scavenging free radicals which reduces inflammation, preventing apoptosis, and protecting brain cells and mitochondria.[ii]
Table of Contents
Saffron (Crocus sativus) as a nootropic is the dried crimson stigma of the C. sativus flower cultivated primarily in Iran.
The earliest reference to Saffron goes back to around 2,300 BC from Sargon, founder of the Akkadian empire. Sargon was born in a village on the shores of the Euphrates called Azupiranu (city of Saffron).[iii]
Since then, documentation of Saffron use over the last 4,000 years for at least 90 illnesses has been uncovered.
Saffron takes a long time to germinate from seed and 3 years for the plant to flower. Once it blooms in mid-Autumn, the flowers must be picked carefully by hand within 1 – 2 weeks.
Each Crocus sativus plant produces 3 – 4 flowers per season. Each flower produces a 3-pronged style, each prong terminating in a vivid crimson stigma. Saffron is the dried stigma of Crocus sativus.
This labor-intensive production method makes Saffron the most expensive culinary spice in the world.
As a nootropic, Saffron may be used for depression, PMS symptoms, post-partum depression, memory, appetite suppression, and preventing neurodegenerative diseases like Parkinson’s and Alzheimer’s.
How does Saffron work in the brain?
Saffron boosts brain health and function in several ways. But two in particular stand out.
- Saffron boosts mood. Recent studies suggest that brain-derived neurotrophic factor (BDNF), Nerve Growth Factor, and cAMP Response Binding Protein (CREB) all play a role in anxiety and depression.
Further research shows that Saffron has a significant effect on BDNF, NFG and cAMP levels in the brain.[v] Which likely explains why Saffron is so effective in treating teenage anxiety and depression.
One study in 2018 had 80 participants aged 12 – 16 years with anxiety and depression try Saffron extract (Affron®) 14 mg or a placebo for 8 weeks.
The study concluded that Saffron extract was effective in relieving the symptoms of separation anxiety, social phobia and depression compared to placebo.[vi]
Researchers in the psychology department at Murdoch University in Perth conducted a systematic analysis of every clinical trial they could find for high-quality, randomized, double-blind studies using Saffron, a placebo and antidepressant meds as controls in humans (not animals).
The team concluded that clinical trials support the use of Saffron for the treatment of mild to moderate depression.[vii]
- Saffron for preventing Alzheimer’s. One of the most common symptoms in Alzheimer’s patients is depression.
And doctors commonly prescribe antidepressants for treatment. Including drugs like sertraline (Zoloft®).[viii] Despite the fact that these meds don’t work for Alzheimer’s disease and come with a host of side effects.[ix]
An alternative treatment is obviously needed. So researchers set up a double-blind, placebo-controlled trial with 46 Alzheimer’s patients. The patients were given 15 mg of Saffron twice daily or placebo for 16 weeks.
The results of this trial showed Saffron produced a significantly better reduction in behavioral and psychological symptoms than placebo. And concluded, “Saffron is both safe and effective in mild to moderate Alzheimer’s”.[x]
The acetylcholinesterase inhibitor donepezil (Aricept®) is also prescribed to Alzheimer’s patients. For increasing acetylcholine which has been found to be low in these patients.
A 22-week, randomized, double-blind trial with 54 Alzheimer’s patients was conducted to compare donepezil with Saffron. Patients received either 15 mg of Saffron twice per day or 5 mg of donepezil twice per day for the extent of the trial.
This phase II study found Saffron extract was as effective as donepezil in the treatment of mild to moderate Alzheimer’s. But Saffron did not produce the side effect of vomiting.[xi]
How things go bad
Depression is a growing health problem. With over 10% of Americans taking prescription antidepressants. Of whom 90% experience at least one adverse effect. Ranging from sexual dysfunction to convulsion to bleeding disorders.
Antidepressant use can result in:
↓ Abnormal bleeding
↓ Agitation, aggression, anxiety, and delirium
↓ Confusion, convulsions and even death
↓ Decreasing memory, delusional thinking
↓ Hallucinations, headaches, and heart attacks
↓ Insomnia, lethargy, nightmares, and panic attacks
↓ Sedation, impaired driving, slow speech
↓ Sexual dysfunction, priapism
↓ Panic attacks, paranoia, suicidal thoughts, violent behavior
↓ Serotonin Syndrome, withdrawal symptoms
A growing database of studies and user reviews show that Saffron helps treat depression without the risky side effects of prescription antidepressants.
Saffron has also been shown to be effective with other conditions for which antidepressants are prescribed. Including anxiety, Alzheimer’s, and obsessive-compulsive disorder (OCD).
To experience Saffron’s nootropic value you’ll need to use more than a sprinkling of the spice from your local supermarket.
Another study with 18 – 45-year-old women suffering from post-partum depression showed Saffron effective in reducing depression.[xiv]
And a group of women aged 18 – 45 dealing with Premenstrual Syndrome (PMS) found that Saffron was effective in relieving depression during two menstrual cycles (cycles 3 and 4).[xv]
Saffron is a smooth muscle relaxant and helps lower blood pressure. Likely because of its inhibitory effect on histamine H1 receptors, stimulatory effect on ß2-adrenoceptors, and antagonist effect on muscarinic receptors.[xvi]
Several human studies show Saffron as effective as some popular antidepressants in treating mild to moderate anxiety and depression.[xix]
Some of the symptoms of Parkinson’s Disease originate from under-utilization of dopamine in the substantia nigra area of the brain. Studies show Saffron helps protect the substantia nigra dopamine neurons associated with Parkinson’s.[xx]
Newly published studies show Saffron helps protect your eyes from ultraviolet blue light radiation (UV-B). And flicker sensitivity from glaring monitors and headlights.[xxi]
Saffron improves the oxygen and nutrient supply required for healthy eyes. By boosting blood flow in the retina and choroid of your eyes.[xxii]
How does Saffron feel?
Saffron has been proven to help with Age-Related Macular Degeneration (AMD). Vision may be sharper. And you can see a line or two further down the Snellen chart at your next eye appointment.
Glare from headlights during nighttime driving and flicker from monitors is no longer a problem.
You may experience an improvement in mood when supplementing with Saffron. No longer over-reacting, and work-related stress now feels like you are again in control.
Many neurohackers report an increase in energy and better libido with Saffron.
Feeling tired and emotional is a thing of the past. You’re back to your bright, positive, happy self!
Saffron Clinical Research
Clinical research into the efficacy of Saffron is encouraging. But trial lengths have typically been limited to 4 – 6 weeks. And sample sizes are relatively small (30 – 40 people).
And keep in mind of the potential for bias because most clinical trials with humans have been conducted in Iran. Which produces nearly 90% of saffron for the world market. But these are still high-quality studies.
Saffron as good as Prozac
A double-blind, randomized trial with 40 adult outpatients suffering from major depression was conducted at the University of Tehran. The study compared Saffron petals with fluoxetine (Prozac®) for the treatment of depression.
Patients were given 15 mg of Saffron petals in the morning and evening, or 10 mg fluoxetine morning and evening for 8 weeks.
The study concluded that Saffron petals were as effective as fluoxetine in the treatment of mild to moderate depression. The remission rate was 25% in both groups with no significant differences in side effects.[xxiii]
Saffron for Alzheimer’s Disease
There is increasing evidence to suggest that Saffron could be used in the management of Alzheimer’s Disease.
In one Iranian study, 54 adults aged 55 year or older with Alzheimer’s participated in a 22-week, double-blind trial. Patients were randomly assigned 30 mg per day of Saffron (15 mg twice per day) or 10 mg per day of donepezil (Aricept®) (5 mg twice per day).
The study found that Saffron was as effective as the drug donepezil in the treatment of mild to moderate Alzheimer’s after 22 weeks.[xxiv]
46 patients with Alzheimer’s volunteered for a 16-week, double-blind trial. Patients were randomly assigned 15 mg of Saffron twice per day or a placebo for the 16-week study.
After 16 weeks, Saffron produced a significantly better outcome on cognitive function than placebo.
The study concluded, “This double-blind, placebo-controlled study suggests that at least in the short-term, Saffron is both safe and effective in mild to moderate Alzheimer’s.”[xxvi]
Saffron for anxiety & depression
60 adult patients with anxiety and depression were given a 50 mg saffron capsule or placebo capsule twice daily for 12 weeks.
Depression and anxiety questionnaires were used at the beginning, 6 and 12 weeks during the trial. The patients who used the saffron supplements had a significant reduction in anxiety and depression symptoms.
The study concluded “Saffron appears to have a significant impact in the treatment of anxiety and depression disorder. Side effects were rare.”[xxvii]
Saffron Recommended Dosage
Clinical studies have evaluated doses ranging from 20 – 400 mg per day of Saffron.
Dosages up to 1.5 g per day of Saffron are thought to be safe.[xxviii] With toxic effects reported for 5 g doses.
As with many nootropics, more is NOT better when using Saffron. Some research shows that dosages above 1.5 g of Saffron can be extremely toxic.
Saffron Side Effects
Genuine Saffron is non-toxic and well-tolerated by most people when used at the recommended dosage.
Some reported side effects of Saffron include headaches, nausea, dizziness, vomiting, and mania (esp. if you are bipolar). Saffron can aggravate asthma symptoms.
5 g of Saffron are associated with toxic effects. And very high doses of Saffron (10 – 20 g) can be deadly.
No drug interactions have been reported. But interactions with anti-aggregating drugs are theoretically possible.
Do NOT use Saffron if you have a bleeding disorder.
Type of Saffron to buy
Saffron as a nootropic is typically sold in capsules.
Most individual Saffron supplements on the market are standardized (for 0.3% safranal) usually with 88.5 mg ‘Saffron extract’.
For nootropic use, look for supplements guaranteed to contain a patented version of Saffron extract. Otherwise, you’ll not likely experience the cognitive benefits of this nootropic for reasons I’ll go into in a minute.
Affron®: Manufactured by PharmActive Biotech Products in Madrid, Spain and not easily found in Saffron products sold in the USA. But here’s one by BCN Health: Saffron Ultra
Satiereal®: Made by PLT Health Solutions in Morristown, NJ and included in select Saffron products like this one by Life Extension: Optimized Saffron
Safranal®: Manufactured by Sigma-Aldrich and included in some Saffron supplements like this one by 1 Body: Saffron 8825
Saffron is also included in much smaller amounts in some vison/eye formulas. While extremely effective for vision health, it’s not enough for much cognitive benefit.
For example, Performance Lab Vision contains 1 mg of Saffron extract. Which I’ve found very effective for reducing glare from computer screens and headlights during nighttime driving. And reducing eye fatigue from monitor flicker. But the dosage in this supplement is too low for any real cognitive benefit.
Keep in mind that Saffron is the most valuable medicinal food plant on the planet. Which makes it a primary target by unscrupulous marketers for adulteration.
Common adulterants include mixing Saffron with things like beet, pomegranate fibers, and red-dyed silk fibers to decrease the cost of Saffron.
Sometimes the flowers of other plants, including safflower, marigold, arnica and tinted grasses are fraudulently mixed with genuine Saffron stigmas.
The common mislabeling of turmeric (curcuma longa) as “Indian saffron”, “American saffron”, or “Mexican saffron” can easily be mistaken as genuine Saffron.
When Saffron is used for therapeutic purposes such as a nootropic supplement, adulteration will make it completely useless or even harmful.[xxix]
Before you buy your Saffron supplement make sure you check that it’s a reputable supplement manufacturer who tests all their raw ingredients and encapsulated product.
This is a classic case of discounted or cheap Saffron is not a bargain. But something else entirely. Buyer beware!
Nootropics Expert Recommendation
I recommend using Saffron as a nootropic supplement.
Your body does not make Saffron on its own. So to get its benefits you must take it as a supplement.
Saffron is especially helpful for suffering from anxiety and depression. Studies show Saffron to be as effective as some popular antidepressants but without the side effects.
If you are currently using antidepressants, Saffron may help alleviate the sexual dysfunction caused by these drugs.
Saffron seems to be an effective way to control appetite. No snacking between meals and you’re no longer obsessed about food.
Saffron has the added benefit of more energy and stamina to help you through your day.
You can safely take up to 200 mg of Saffron daily if needed. But dosed 100 mg at a time. Be familiar with the associated side effects of higher doses of Saffron.
For nootropic use, choose a patented form of Saffron supplement such as the ones I’ve described above under “Available Forms”.
Saffron is also a very effective vision supplement. Driving at night is easier on your eyes. And the flicker caused by screens and monitors won’t leave you with eye fatigue later in the day.
For a great vision supplement, I highly recommend Performance Lab Vision.
For nootropic benefit look for genuine, verified pure Saffron or Saffron extract (standardized to 0.3 or 0.1% safranal).
[i] Hosseinzadeh H., Noraei N.B. “Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice.” Phytotherapy Research. 2009 Jun;23(6):768-74 (source)
[v] Ghasemi T., Abnous K., Vahdati F., Mehri S., Razavi B.M., Hosseinzadeh H. “Antidepressant Effect of Crocus sativus Aqueous Extract and its Effect on CREB, BDNF, and VGF Transcript and Protein Levels in Rat Hippocampus.” Drug Research (Stuttgart). 2015 Jul;65(7):337-43. (source)
[vi] Lopresti A.L., Drummond P.D., Inarejos-García A.M., Prodanov M. “affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study.” Journal of Affective Disorders. 2018 May;232:349-357 (source)
[vii] Lopresti A.L., Drummond P.D. “Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action.” Human Psychopharmacology. 2014 Nov;29(6):517-27. (source)
[ix] Banerjee S., Hellier J., Romeo R., et al. “Study of the use of antidepressants for depression in dementia: the HTA-SADD trial - a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.” Health Technology Assessment. 2013 Feb;17(7):1-166. (source)
[x] Akhondzadeh S., Sabet M.S., Harirchian M.H., Togha M., Cheraghmakani H., Razeghi S., Hejazi S.Sh., Yousefi M.H., Alimardani R., Jamshidi A., Zare F., Moradi A. “Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.” Journal of Clinical Pharmacy and Therapeutics. 2010 Oct;35(5):581-8. (source)
[xi] Akhondzadeh S., Shafiee Sabet M., Harirchian M.H., Togha M., Cheraghmakani H., Razeghi S., Hejazi S.S., Yousefi M.H., Alimardani R., Jamshidi A., Rezazadeh S.A., Yousefi A., Zare F., Moradi A., Vossoughi A. “A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.” Psychopharmacology (Berlin). 2010 Jan;207(4):637-43. (source)
[xii] Noorbala A.A., Akhondzadeh S., Tahmacebi-Pour N., Jamshidi A.H. “Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial.” Journal of Ethnopharmacology. 2005 Feb 28;97(2):281-4 (source)
[xiii] Mazidi M., Shemshian M., Mousavi S.H., Norouzy A., Kermani T., Moghiman T., Sadeghi A., Mokhber N., Ghayour-Mobarhan M, Ferns G.A. Journal of Complementary and Integrative Medicine. 2016 Jun 1;13(2):195-9 (source)
[xiv] Kashani L., Eslatmanesh S., Saedi N., Niroomand N., Ebrahimi M., Hosseinian M., Foroughifar T., Salimi S., Akhondzadeh S. “Comparison of Saffron versus Fluoxetine in Treatment of Mild to Moderate Postpartum Depression: A Double-Blind, Randomized Clinical Trial.” Pharmacopsychiatry. 2017 Mar;50(2):64-68. (source)
[xv] Hosseini M., Kashani L., Aleyaseen A., Ghoreishi A., Rahmanpour H., Zarrinara A.R., Akhondzadeha S. “Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double‐blind, randomised and placebo‐controlled trial” International Journal of Obstetrics and Gynecology 06 February 2008 (source)
[xvi] Mokhtari-Zaer A., Khazdair M.R., Boskadbady M.H. “Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms” Avidenna Journal of Phytomedicine 2015 Sep-Oct; 5(5): 365–375. (source)
[xvii] Geromichalos G.D., Lamari F.N., Papandreou M.A., Trafalis D.T., Margarity M., Papageorgiou A., Sinakos Z. “Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies.” Journal of Agriculture and Food Chemistry. 2012 Jun 20; 60(24):6131-8. (source)
[xviii] Papandreou M.A., Kanakis C.D., Polissiou M.G., Efthimiopoulos S., Cordopatis P., Margarity M., Lamari F.N. “Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents.” Journal of Agriculture and Food Chemistry 2006 Nov 15; 54(23):8762-8. (source)
[xix] Khazadair M.R., Boskabady M.H., Hosseini M., Rezaee R., Tsatsakis A.M. “The effects of Crocus sativus (saffron) and its constituents on nervous system: A review” Avicenna Journal of Phytomedicine. 2015 Sep-Oct; 5(5): 376–391 (source)
[xx] Purushothuman S., Nandasena C., Peoples C.L., El Massri N., Johnstone D.M., Mitrofanis J., Stone J. “Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-Treated mice.” Journal of Parkinson’s Disease. 2013; 3(1):77-83. (source)
[xxi] Natoli R., Zhu Y., Valter K., Bisti S., Eells J., Stone J. “Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina.” Molecular Vision. 2010 Sep 3;16:1801-22. (source)
[xxii] Xuan B., Zhou Y.H., Li N., Min Z.D., Chiou G.C. “Effects of crocin analogs on ocular blood flow and retinal function.” Journal of Ocular Pharmacology & Therapeutics. 1999 Apr;15(2):143-52. (source)
[xxiii] Akhondzadeh Basti A., Moshiri E., Noorbala A.A., Jamshidi A.H., Abbasi S.H., Akhondzadeh S. “Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial.” Progress in Neuropsychopharmacology and Biological Psychiatry. 2007 Mar 30;31(2):439-42. (source)
[xxiv] Akhondzadeh S., Shafiee Sabet M., Harirchian M.H., Togha M., Cheraghmakani H., Razeghi S., Hejazi S.S., Yousefi M.H., Alimardani R., Jamshidi A., Rezazadeh S.A., Yousefi A., Zare F., Moradi A., Vossoughi A. “A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.” Psychopharmacology (Berlin). 2010 Jan;207(4):637-43. (source)
[xxvi] Akhondzadeh S., Sabet M.S., Harirchian M.H., Togha M., Cheraghmakani H., Razeghi S., Hejazi S.Sh., Yousefi M.H., Alimardani R., Jamshidi A., Zare F., Moradi A. “Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.” Journal of Clinical Pharmacy and Therapeutics. 2010 Oct;35(5):581-8. (source)
[xxvii] Mazidi M., Shemshian M., Mousavi S.H., Norouzy A., Kermani T., Moghiman T., Sadeghi A., Mokhber N., Ghayour-Mobarhan M., Ferns G.A. “A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression.” Journal of Complementary and Integrative Medicine. 2016 Jun 1;13(2):195-9. (source)
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