St. John's wort dosage

St. John’s wort

David Tomen
David Tomen
19 minute read
St. John’s wort has been shown to relieve depression as well as some prescription antidepressants

St. John’s wort (hypericum perforatum) is a potent antidepressant. This sprawling, leafy herb grows throughout much of the world’s temperate regions.

St. John’s wort has been used to treat a variety of internal and external illnesses dating back to the ancient Greeks. St. John’s wort supplements are derived from the flowering tops of this perennial shrub.St. John's wort treats depression

The name St. John’s wort comes from its traditional flowering and harvesting on St. John’s Day which falls on June 24.

St. John’s wort has remained a popular treatment for anxiety, depression, cuts, and burns. Recent research shows its effectiveness in treating cancer, inflammation, bacterial and viral diseases.

As a nootropic, and for cognitive health, St. John’s wort is as effective at relieving mild-to-moderate depression as the most commonly prescribed SSRI and TCA (tricyclic) antidepressants.

St. John’s wort helps:

  • Neurotransmitters. St. John’s wort inhibits the uptake of serotonin, dopamine, GABA, glutamate and norepinephrine. Inhibiting the neuronal uptake of these neurotransmitters can have a profound effect on depression and mood.
  • Neuroprotection. St. John’s wort extract decreases oxidative stress, prevents neurotoxicity, and brain inflammation. It helps maintain mitochondria electric potential in brain cells. And protects against cell death caused by amyloid P peptides that form plaques in the brains of those suffering from Alzheimer’s.
  • Anxiety and stress. St. John’s wort extract helps alleviate the symptoms of anxiety and stress by influencing neurotransmitters. And St. John’s wort moderates the genes controlling the function of your HPA-axis which is directly related to symptoms of anxiety and stress.


St. John’s wort (hypericum perforatum) is regarded as a wildflower, herb and weed. As a nootropic, St. John’s wort is considered a powerful antidepressant.

St John's wort - Hypericum perforatum
St. John’s wort (Hypericum perforatum)

St. John’s wort is native to Europe. But can be found growing wild throughout Asia, Africa, North and South America and Australia.

Greek physicians Galen and Dioscorides prescribed St. John’s wort as a diuretic, for healing wounds and treating menstrual disorders. In the Middle Ages, it was used as a talisman for warding off evil spirits.

St. John’s wort is best harvested on St. John’s Day (June 24) when the herb is in peak bloom. Legend has it that if you placed a sprig of the herb under your pillow on St. John’s Eve, St. John himself may appear in a dream, and bless you for another year. (Not sure if this applies when you put a bottle of St. John’s wort extract under your pillow, but worth a try).

St. John’s wort first crossed the radar of modern herbalists and naturopaths in 1997. A study published in the British Medical Journal entitled, “St John’s wort for depression–an overview and meta-analysis of randomized clinical trials” pushed it to superstar herbal antidepressant status.

This meta-analysis of 23 previously published studies on St. John’s wort was drawn from foreign medical journals. The analysis showed that overall, St. John’s wort was significantly superior to placebo. And was as effective as pharmaceutical antidepressants.[i]

The British Medical Journal published another study in 2005 showing that St. John’s wort was equally effective in treating depression and better tolerated than the widely prescribed antidepressant paroxetine (Paxil).[ii]

The two major active constituents of St. John’s wort are hypericin (a naphthodianthrone) and hyperforin (a phloroglucinol). The plant contains a total of seven groups of medicinally active compounds.[iii]

Researchers have extensively documented St. John’s wort as having antidepressant, antiviral, antioxidant, anti-cancer, and antibacterial effects.[iv]

The most recent clinical studies show that hyperforin is the constituent in St. John’s wort that has the most antidepressant action.

If you’ve had limited success using St. John’s wort for depression and anxiety, your choice of supplement may be the problem. Go to “Dosage Notes” in this article to learn what extracts work best.


How does St. John’s wort Work in the Brain?

St. John’s wort boosts brain health and function in several ways. But two in particular stand out.

  1. St. John’s wort reduces depression. Hyperforin is the major antidepressive constituent of St. John’s wort. Hyperforin inhibits the uptake of serotonin, dopamine and norepinephrine in the brain.[v] By making more of each of these neurotransmitters available in the brain, mood is elevated and depressive symptoms decline.

Clinical trials also demonstrate that the level of antidepressant effect of St. John’s wort extract is entirely dependent on the concentration of hyperforin.[vi]

A study in Berlin compared the efficacy of using St. John’s wort extract (WS 5570) to paroxetine (Paxil) in treating moderate to severe depression.

In this multicenter, randomized, double-blind study, 130 patients who received 900 mg or 1800 mg per day of St. John’s wort, or 40 mg of paroxetine were included.

The study showed that St. John’s wort and paroxetine were equally effective in preventing relapse in continuation of treatment after recovery from moderate to severe depression. And that St. John’s wort was an important alternative treatment option for long-term prevention of depression.[vii]

  1. St. John’s wort reduces stress. St. John’s wort is licensed in Germany to treat anxiety, depression and sleep disorders. But scientists and researchers are still working on what in this plant provides the anxiolytic effects.

The anti-anxiety effects of St. John’s wort have been attributed to the binding affinity of at least 10 different extracts of the herb. Including naphthodianthrones like hypericin, flavonoids, xanthones, and bioflavonoids for adenosine triphosphate (ATP). GABAA, GABAB and glutamine receptors, as well as the inhibition of monoamine Oxidase-A and -B activity.  And synaptic uptake of serotonin, dopamine and norepinephrine.[viii]

All we know for sure at this point is that St. John’s wort works to help alleviate some forms of anxiety. One German study ran a multicenter, randomized, placebo controlled, 6-week trial comparing the efficacy of St. John’s wort extract LI 160 (600 mg/day), and placebo in 151 out-patients suffering from anxiety.

The data from the trial shows that St. John’s wort extract (LI 160) has superior effectiveness in controlling anxiety symptoms. And tolerability of the extract was excellent.[ix]

How things go bad

Depression can be experienced at any age. Imbalances in neurotransmitters including serotonin, dopamine, and norepinephrine can affect everything from cognition to mood.St-Johns-wort-reviews

Memory, recall, reaction time and mood diminish

Neuroreceptors decline

↓ Neurotransmitters levels decline

↑ Anxiety, panic attacks, stress and insomnia rise

Neuroplasticity declines degrading long-term potentiation

Under conditions of depression and chronic stress your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition, and decision-making all suffer as a result.

St. John’s wort benefits

St. John’s wort inhibits synaptic uptake in your brain of serotonin, dopamine, and norepinephrine with approximately equal affinity.

Research shows that St. John’s wort also has an affinity for adenosine (ATP), GABA and glutamate receptors. And in the lab, scientists discovered it downregulates beta-adrenergic receptors and upregulates serotonin receptors.[x]

Adrenergic receptors are a class of G protein receptors that are targets of the catecholamines like norepinephrine and epinephrine (adrenaline). This upregulation and downregulation of neurotransmitter concentrations are in areas of the brain implicated in depression.

And finally, neuroendocrine studies show that St. John’s wort is involved in the regulation of genes that control HPA-axis function. Also contributing to the antidepressant action of this herb.[xi]

Much of the therapeutic activity is attributable to St. John’s wort active phytochemical ingredients hypericin, hyperforin and several flavonoids.[xii]

This novel mechanism of action is unlike any other single pharmaceutical antidepressant or nootropic. And underlies St. John’s wort’s profound effect on depression.

St. John’s wort also has strong antibacterial[xiii] and antiviral[xiv] properties. St. John’s wort inhibits tumor cell growth.[xv]

Research shows that St. John’s wort extracts decrease oxidative stress and prevent neurotoxicity, and inflammation. And may be an effective treatment for oxidative stress-related neurodegenerative disorders like Parkinson’s and Alzheimer’s.[xvi]

St. John’s wort shows promise as an anti-inflammatory.[xvii] Thousands of years of clinical use shows St. John’s wort works as a wound-healing agent.

And St. John’s wort even helps reduce the effects of opium dependence by reducing withdrawal symptoms.[xviii] Handy if you’re coming off of opiates.


How does St. John’s wort feel?

If you have had problems with using SSRI prescription antidepressants, St. John’s wort extract may be a good option for you.

St. John’s wort does not produce the same side effects as pharmaceutical antidepressants. Sex drive is not affected. No withdrawal symptoms when you stop taking St. John’s wort.

Users of St. John’s wort extract say it often works sooner than expected, and gets better over time.

St. John’s wort extract helps provide better focus, and fewer Obsessive-Compulsive Disorder (OCD) symptoms. Users report an end to procrastination, less irritation, and better mood.

St. John’s wort extract takes the edge off situations that would normally stress you. Feelings of anxiety are less or non-existent.

Women going through menopause report feeling more emotionally stable when using St. John’s wort extract. Mood swings are no longer an issue.

If you deal with PTSD you may find that St. John’s wort extract will put a stop to the rage. And long-term depression could be a distant memory.

If you are sure your depression is caused by a serotonin imbalance, you should feel the mood-lifting effects of St. John’s wort.

But neuroscience is a complicated subject. And everyone’s body and wiring are different. St. John’s wort does not work for all types of depression or anxiety.

If your depression is caused by a hormone imbalance, a depleted microbiome, an issue with dopamine levels or other neuroreceptor issue, you may not experience the benefit of St. John’s wort.

And please, please do not combine St. John’s wort with prescription antidepressants! Serotonin Syndrome is real and could kill you. Literally.


The Research

The Politics of Treatment for Depression

Most clinical studies using St. John’s wort for depression have been conducted in Europe. And were targeted in cases of mild to moderate depression.

And then came a study done at Vanderbilt University in the US in 2001 which made headline news and created a ton of controversy. This study discredited the herb’s use in treating patients with major depression.

I’m including this study to draw your attention to why we cannot always rely on “clinical studies” to study a nootropic’s efficacy in brain optimization. And why the nootropics community often resorts to personal experience, and the reviews of other neurohackers.

This double-blind, placebo-controlled trial worked with 200 adult outpatients (mean age 42.4 years) who were diagnosed with major depression. Patients were randomly assigned to receive 900 mg per day of St. John’s wort extract or a placebo for 4 weeks. And if they did not respond, the dose was raised to 1,200 mg per day (or a placebo) for another 8 weeks.

The researchers concluded that there was no significant change in patient depression scores. And that St. John’s wort was no better than placebo for treating major depression.

Their conclusion was, “St. John’s wort was not effective for treatment of major depression”.[xix]

I bring this study up for one reason: the study was funded by Pfizer, the pharmaceutical manufacture of Zoloft. The leading synthetic antidepressant medication.

In 2015, the FDA in the US pushed Pfizer Inc. to modify the safety warning for Zoloft®. Linking Zoloft to causing heart defects in newborns. This in response to hundreds of lawsuits by women who say they weren’t adequately warned that Zoloft could cause defects in their newborns.

Zoloft sales for Pfizer made the company $3.3 billion in 2005.[xx]

It seems to me that having a major pharmaceutical company funding the study of an herb that is in direct competition to one of their main profit-centers is a direct conflict of interest. And there was no way Pfizer was going to have a clinical trial show that St. John’s wort was as good as, or better than Zoloft.

It’s also interesting that sales of St. John’s wort annual USA sales reached a peak of $315 million in 1998. But had declined to about $60 million by 2006.[xxi] Bad press strongly affected the sales of this natural antidepressant. And yet the sales of pharmaceutical antidepressants continue to rise.

St. John’s wort as a Treatment for Mild-to-Moderate Depression

A study at St. John’s Episcopal Hospital in New York compared St. John’s wort to the SSRI sertraline (Zoloft®) in the treatment of depression.

In this double-blind, randomized study, 30 outpatients (mean age 45.5 years) with mild to moderate depression received 600 mg per day of standardized St. John’s wort extract or 50 mg per day of sertraline for 1 week.

This was followed by 900 mg per day of St. John’s wort extract or 75 mg per day of sertraline for another 6 weeks.

The severity of depression symptoms was significantly reduced in both treatment groups. Clinical response was noted in 47% of patients receiving St. John’s wort. And 40% in patients receiving sertraline.

The researchers concluded that St. John’s wort extract was at least as effective as sertraline in the treatment of mild to moderate depression.[xxii]

St. John’s wort for Major Depression

I include this study done in 2008 for using St. John’s wort as treatment for major depression as a response to the questionable study sponsored by Pfizer in 2001.

This study done in Munich, Germany investigated whether extracts of St. John’s wort are more effective than placebo in treating major depression. And as effective with fewer side effects than standard antidepressant drugs.

This study was a review of 29 trials including a total of 5,489 patients. It included 18 comparisons with placebo and 17 comparisons with synthetic “standard antidepressants”. The standard antidepressants included tricyclic and SSRI antidepressants.

The author’s conclusions reported that the available evidence suggests that St. John’s wort extracts were superior to placebo in patients with major depression. St. John’s wort extracts were similarly effective as standard antidepressants. And St. John’s wort extracts had fewer side effects than standard antidepressants.[xxiii]

St. John’s wort helps OCD

A study done at the Dean Foundation for Health Research and Education analyzed 12 patients who had been diagnosed with OCD. Patients received 450 mg of St. John’s wort twice daily for 12 weeks.

The study included weekly evaluations using three different Obsessive-Compulsive scales. And a monthly evaluation with the Hamilton Rating Scale for Depression.

Changes in obsessive compulsive behavior occurred within one week of supplementing with St. John’s wort. And changes continued to improve over the course of the 12-week trial.

5 of the 12 patients were rated “much” or “very much” improved, 6 patients were rated “minimally” improved, and 1 person had no change in symptoms.

The researchers concluded that St. John’s wort could be an effective treatment for Obsessive-Compulsive Disorder (OCD).[xxiv]

St. John’s wort recommended dosage

St. John’s wort is available from local health food and vitamin stores and online. St. John’s wort comes in capsule, tablet and powder form. It’s also available as tinctures, teas and oil-based lotions.St. John's wort dosage

Most St. John’s wort supplements are standardized to contain 3% hypericin. But the most recent clinical studies show that hyperforin is the constituent in St. John’s wort that has the most antidepressant action.

Researchers say that the benefits of St. John’s wort are only applicable to standardized extracts such as LI 160, WS 5570/2, and ZE 117.[xxv]

Check the labels and look for:

  • Perika® which is WS 5570 extract
  • Kira® which is LI 160 extract
  • New Chapter SC27 who produce their own extract

There are reports and some clinical data which suggest that the photosensitivity caused by hypericin can cause cataracts and blindness. All the more reason to play it safe, and go with a high quality St. John’s wort extract containing hyperforin.[xxvi]

Recommended doses for St. John’s wort extract:

  • St. John’s wort for anxiety: 900 mg twice daily
  • St. John’s wort for mild to moderate depression: 300 mg 3-times daily
  • St. John’s wort for severe depression: 900 – 1800 mg daily
  • St. John’s wort for OCD: 450 – 1800 mg daily for 12 weeks
  • St. John’s wort for PMS: 300 – 900 mg daily for 2 menstrual cycles
  • St. John’s wort for irritable bowel syndrome: 450 mg twice daily for 12 weeks
  • St. John’s wort for nerve pain: three 900 mcg hypericin tablets for 2 treatment periods of 5 weeks each

St. John’s wort side effects

Side effects with St. John’s wort are generally mild and can include stomach upset, hives, skin rashes, fatigue, restlessness, headache, dry mouth, dizziness and confusion.

Research shows the Hyperforin found in St. John’s wort is a potent noncompetitive inhibitor of CYP2D6 activity and competitive inhibitor of CYP2C9 and CYP3A4 activity. And Hypericin also demonstrated potent inhibition of several CYP activities.

A researcher working in Pfizer’s Central Research Division said this, “These in vitro data indicate that St. John’s wort preparations contain constituents that can potently inhibit the activities of major human drug-metabolizing enzymes and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo.

As a neurohacker this means that St. John’s wort can either potentiate the effectiveness of some of the nootropics in your stack, or prescription drugs you are using. Or can prevent you from experiencing the benefits of a nootropic supplement or med. 

St. John’s wort can interfere with getting pregnant, or make infertility worse. It can make ADHD symptoms worse. Particularly if you’re taking Ritalin.

St. John’s wort may increase the risk of psychosis in those with schizophrenia, and may contribute to dementia in those with Alzheimer’s.

St. John’s wort can interact with medications used during surgery. So if you’re anticipating surgery avoid St. John’s wort.

Do not take St. John’s wort if you have bipolar disorder.

Some St. John’s wort extracts can make your skin and eyes overly sensitive to sunlight. You should avoid sunlamps, tanning booths and tanning beds while using a St. John’s wort product containing hypericin.

There is some clinical data showing that St. John’s wort products that contain hypericin may cause blindness.[xxvii]

St. John’s wort and Serotonin Syndrome

Cytochrome P450 3A4 (CYP3A4) is a liver enzyme whose job is to oxidize small, foreign organic molecules and toxins so they can be removed from your body.

Some substances, including St. John’s wort and grapefruit juice, affect the enzyme CYP3A4. And can amplify or weaken the action of those drugs and nootropics.[xxviii]

St. John’s wort interacts with tricyclic, SSRI and MAOI antidepressants. Taking St. John’s wort with these medications increases their action, and could lead to serotonin syndrome which can be deadly.

Do not take St. John’s wort with antidepressants including:

  • Tricyclic: Amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil)
  • SSRI: Citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil), fluoxetine (Prozac), sertraline (Zoloft)
  • MAOI’s: (Phenelzine (Nardil), tranylcypromine (Parnate)

St. John’s wort can reduce levels of antihistamines in your body. It can increase the risk of bleeding when combined with Plavix and birth control pills. Do not use St. John’s wort with Warfarin as it can reduce its effectiveness.

Drugs that suppress the immune system can lose their effectiveness with St. John’s wort. It should not be used with drugs that treat HIV and AIDS.

St. John’s wort can increase the sedative effect of barbiturates, benzodiazepines (Valium), and triptans that treat migraines.

St. John’s wort also interacts with antifungal drugs, statins, calcium channel blockers, and any other medication that is broken down by the liver. Which covers a lot of drugs and nootropics.

Serotonin Syndrome is not to be messed with. An overload of serotonin in your brain can make you very sick. And can ultimately kill you. We’re not kidding here.

If you suspect anything could cause problems if it’s increased or decreased in your system, do not use St. John’s wort. If your goal is to treat depression and mood issues, you have many other safer options available to you.

Type of St. John’s wort to buy

St. John’ wort is available in tablet, capsule and powder form. Most are standardized to contain 0.3% hypericin. But the most recent clinical studies show that hyperforin is the constituent in St. John’s wort that has the most antidepressant action.

Researchers say that the benefits of St. John’s wort are only applicable to standardized extracts such as LI 160, WS 5570/2, and ZE 117.[xxix]

Check the labels and look for a product containing:

  • Perika® which is WS 5570 extract
  • Kira® which is LI 160 extract
  • New Chapter SC27 who produce their own extract

St. John’s wort is also available in tinctures, teas and oil-based skin lotions.

Nootropics Expert Recommendation

St. John’s wort extract up to 900 – 1,800 mg per day

Nootropics Expert Tested and ApprovedI recommend using St. John’s wort extract as a nootropic supplement. But with the strongest warning we’ve issued for any nootropic mentioned on Nootropics Expert®.

Do not combine St. John’s wort with prescription antidepressants because the combination puts you in serious danger of Serotonin Syndrome.

St. John’s wort may also nullify or amplify the effects of other drugs including nootropics in your stack. This is caused by the suppression or induction of certain enzymes in your liver.

Check the “Side Effects” portion of this article. And do your research before using St. John’s wort if you are taking any other medication or nootropic. Including the section on how St. John’s wort can either increase the effectiveness of some nootropics and prescription meds. Or prevent you from experiencing their benefits depending on the supplement or drug. Because of its effects on liver enzymes.

Your body does not make St. John’s wort on its own. So to experience its antidepressant effects, you must take it as a supplement.

St. John’s wort is especially helpful for those suffering from depression, anxiety and stress. Studies show it may help stop and reverse the devastating effects of stress on your brain, and body.

St. John’s wort stacks well with SAM-e.

You can safely take up to 1,800 mg of St. John’s wort daily if needed. Half the dose first thing in the morning. And the other half early afternoon. St. John’s wort can cause insomnia. So avoid taking it too late in the day.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] Linde K., Ramirez G., Mulrow C.D., Pauls A., Weidenhammer W., Melchart D. “St John’s wort for depression–an overview and meta-analysis of randomised clinical trials.” British Medical Journal 1996 Aug 3;313(7052):253-8. (source)

[ii] Szegedi A, Kohnen R, Dienel A, Kieser M, “Acute Treatment of Moderate to Severe Depression with Hypericum Extract WS(R) 5570 (St. John’s Wort):  Randomized, Controlled, Double-Blind, Non-Inferiority Trial versus Peroxetine”, British Medical Journal 2005, BMJ Online First Retrieved July 29, 2016 (source)

[iii] Nahrstedt A., Butterweck V. “Biologically active and other chemical constituents of the herb of Hypericum perforatum L.”Pharmacopsychiatry. 1997 Sep;30 Suppl 2:129-34. (source)

[iv] Barnes J., Anderson L.A., Phillipson J.D. “St John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties.” Journal of Pharmacy and Pharmacology. 2001 May;53(5):583-600. (source)

[v] Müller W.E., Singer A., Wonnemann M. “Hyperforin–antidepressant activity by a novel mechanism of action.” Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S98-102. (source)

[vi] Laakmann G., Schüle C., Baghai T., Kieser M. “St. John’s wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy.” Pharmacopsychiatry. 1998 Jun;31 Suppl 1:54-9. (source)

[vii] Anghelescu I.G., Kohnen R., Szegedi A., Klement S., Kieser M. “Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study.”Pharmacopsychiatry. 2006 Nov;39(6):213-9. (source)

[viii] Butterweck V. “Mechanism of action of St John’s wort in depression: what is known?” CNS Drugs. 2003;17(8):539-62. (source)

[ix] Volz H.P., Murck H., Kasper S., Möller H.J. “St John’s wort extract (LI 160) in somatoform disorders: results of a placebo-controlled trial.”Psychopharmacology (Berlin). 2002 Nov;164(3):294-300 (source)

[x] Klemow K.M., Bartlow A., Crawford J., Kocher N., Shah J., Ritsick M. “Chapter 11Medical Attributes of St. John’s Wort (Hypericum perforatum)” Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. (source)

[xi] Butterweck V., Hegger M., Winterhoff H. “Flavonoids of St. John’s Wort reduce HPA axis function in the rat.” Planta Medica. 2004 Oct;70(10):1008-11. (source)

[xii] Butterweck V. “Mechanism of action of St John’s wort in depression: what is known?” CNS Drugs. 2003;17(8):539-62. (source)

[xiii] Schempp C.M., Pelz K., Wittmer A., Schöpf E., Simon J.C. “Antibacterial activity of hyperforin from St John’s wort, against multiresistant Staphylococcus aureus and gram-positive bacteria.”Lancet. 1999 Jun 19;353(9170):2129. (source)

[xiv] Tang J., Colacino J.M., Larsen S.H., Spitzer W. “Virucidal activity of hypericin against enveloped and non-enveloped DNA and RNA viruses.” Antiviral Research. 1990 Jun;13(6):313-25. (source)

[xv] Schempp C.M., Kirkin V., Simon-Haarhaus B., Kersten A., Kiss J., Termeer C.C., Gilb B., Kaufmann T., Borner C., Sleeman JP, Simon J.C. “Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John’s wort that acts by induction of apoptosis.” Oncogene. 2002 Feb 14;21(8):1242-50. (source)

[xvi] Zou Y.P., Lu Y.H., Wei D.Z. “Protective effects of a flavonoid-rich extract of Hypericum perforatum L. against hydrogen peroxide-induced apoptosis in PC12 cells.” Phytotherapy Research. 2010 Jan;24 Suppl 1:S6-S10. (source)

[xvii] Tedeschi E., Menegazzi M., Margotto D., Suzuki H., Förstermann U., Kleinert H. “Anti-inflammatory actions of St. John’s wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha (STAT-1alpha) activation.” Journal of Pharmacology and Experimental Therapy. 2003 Oct;307(1):254-61 (source)

[xviii] Feily A., Abbasi N. “The inhibitory effect of Hypericum perforatum extract on morphine withdrawal syndrome in rat and comparison with clonidine.” Phytotherapy Research. 2009 Nov;23(11):1549-52 (source)

[xix] Shelton R.C., et. Al. “Effectiveness of St John’s wort in major depression: a randomized controlled trial.” JAMA. 2001 Apr 18;285(15):1978-86. (source)

[xx] Feeley J., Koons C. “Pfizer Weighing FDA Request to Change Zoloft’s Warnings” Bloomberg News Retrieved July 28, 2016 (source)

[xxi] Tilburt J.C., Emanuel E.J., Miller F.G. “Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results.” Journal of General Internal Medicine. 2008 Sep;23(9):1495-8. (source)

[xxii] Brenner R., Azbel V., Madhusoodanan S., Pawlowska M. “Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.”Clinical Therapy. 2000 Apr;22(4):411-9. (source)

[xxiii] Linde K., Berner M.M., Kriston L. “St John’s wort for major depression.” Cochrane Database of Systematic Revues. 2008 Oct 8;(4):CD000448 (source)

[xxiv] Taylor L.H., Kobak K.A. “An open-label trial of St. John’s Wort (Hypericum perforatum) in obsessive-compulsive disorder.” Journal of Clinical Psychiatry. 2000 Aug;61(8):575-8. (source)

[xxv] Klemow K.M., Bartlow A., Crawford J., Kocher N., Shah J., Ritsick M. “Chapter 11Medical Attributes of St. John’s Wort (Hypericum perforatum)” Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. (source)

[xxvi] Wielgus A.R., et. Al. “Phototoxicity in Human Retinal Pigment Epithelial Cells Promoted by Hypericin, a Component of St. John’s Wort”Photochemical Photobiology. 2007; 83(3): 706–713. (source)

[xxvii] Booth J.N. 3rd., McGwin G. “The association between self-reported cataracts and St. John’s Wort.” Current Eye Research. 2009 Oct;34(10):863-6. (source)

[xxviii] Wenk M., Todesco L., Krähenbühl S. “Effect of St John’s wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females.” British Journal of Clinical Pharmacology. 2004 Apr;57(4):495-9. (source)

[xxix] Klemow K.M., Bartlow A., Crawford J., Kocher N., Shah J., Ritsick M. “Chapter 11Medical Attributes of St. John’s Wort (Hypericum perforatum)” Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. (source)

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Join The Discussion - 230 comments

April 2, 2020

Hey David,

I want to start taking St John’s Wort for anxiety/depression/ocd, however I am torn because of the photosensitivity warning. The weather is getting nice now and I love to get into the sunlight. Do you think I should still attempt to use SJW and see if photosensitivity is a problem? For reference, I am caucasian with dark hair and dark eyes and don’t consider myself to be fair-skinned. Also, what do you recommend as a substitute for SJW? I currently take no medications and have been supplementing with ashwaganda, Vit D, & B12. I appreciate any feedback, thanks!

    David Tomen
    April 23, 2020

    Sarah, St. John’s wort inhibits the uptake of serotonin, dopamine, GABA, glutamate and norepinephrine. So it’s kinda’ like the Swiss Army Knife of nootropics when it comes to boosting all the major neurotransmitters. The only way to replace it is to find out which neurotransmitter you are low in and go with a precursor to boost that particular one.

    The only way to find out which one is your issue you need to try them one at a time until you feel better. For example, L-Tryptophan for serotonin, L-Tyrosine for dopamine and norepinephrine, GABA for GABA, and L-Glutamine for glutamate.

March 23, 2020

what does st johns stack well with and what is a no-no?

i also take

lions main

just based on what im feeling now it does not go with modafinil.

what about racetams?

Also, thanks for all the awesome info.

    David Tomen
    March 23, 2020

    Solomon, shouldn’t be a problem with the racetams either. This biggest no-no is using it with anything that directly or strongly supports serotonin. For example, you wouldn’t want to use it with 5-HTP or L-Tryptophan.

    The key going forward and figuring this out for yourself is understanding the “mechanism of action” for St. John’s wort. And the “mechanism of action”, or in my language “How ____ works in the brain” for each supplement you are using or intend to try.

      March 24, 2020

      Thanks for the quick reply,

      why is st johns rarely included in pre-made stacks if it is backed by so much solid research and acts as well as an ssri, why isnt it in mind labs pro for example? I have the same question about sam-e….I also remember reading a post of your somewhere suggesting l tryptophan instead of st johns?

      On another note can you suggest a book than discusses in normal English which neurotransmitters correspond to which emotion and the general process of how the brain works, (you can suggest your own too 🙂

      Lastly i would like to thank you for all of this priceless information. I am a Rabbi and Therapist/life coach, and everything you say is golden for my own health as well as my clients.

        David Tomen
        March 24, 2020

        Solomon, I have a chapter that covers neurotransmitters in my book Head First.

        St. John’s wort is not usually offered in pre-made nootropic stacks because it is very potent. And could cause problems for a lot of people who don’t know how to use it. And because it is contraindicated with a lot of prescription medications that affect serotonin.

        L-Tryptophan is a far safer way to increase serotonin levels.

        And SAM-e acts as a cofactor in the synthesis of some neurotransmitters. Not an obvious choice for a nootropic stack.

January 8, 2020

I’m looking for the best Nootropic for social anxiety. I don’t take SSRI’s

Raheem Jr
December 10, 2019

Hi sir. Thank you for your input and this helpful article. I used SSRIs years ago. about 10, 11 years ago and it was for a pretty short period of time. I now wanna try ST john’s wort. As recommended by you. I purchased the Nature’s way Perika extract. Am I gonna be safe from serotonin syndrome ? And how much should I take daily for moderate to severe depression ? Also does ST John’s cause insomnia? I also use CBD oil daily and was wondering if that interferes with ST John’s?
Thank you in advance

    David Tomen
    December 12, 2019

    Raheem, CBD Oil and St. John’s wort both affect serotonin. Not sure if it’s enough to cause Serotonin Syndrome but I’d be careful until you find out for sure. Possibly ask the CBD Oil manufacturer for their opinion.

    St. John’s wort dosage for mild to moderate depression is 300 mg 3-times daily. But CBD Oil could increase its mechanism of action so you’d need less. Please contact the company you got your CBD Oil from and make sure you talk to someone who has knowledge about contraindications.

October 21, 2019

Really appreciate the resources here & your assistance.
Question – Would it be alright to take St John’s Wort + Panax Ginseng + Coluracetam, simultaneously? I am concerning of serotonin syndrome.

Generalized anxiety disorder. Had adverse reaction to SSRI, so am looking for natural alternatives. Boosting serotonin is apparently key for lowering my related vestibular (dizziness) symptoms.

Thank you!

    David Tomen
    October 21, 2019

    CC, not likely a good idea but Serotonin Syndrome is really nasty. Why don’t you replace St. John’s wort with L-Tryptophan? That’s a much safer way to raise serotonin.

      Chelsea Cowan
      October 22, 2019

      Many thanks! 🙂

Robert L.
September 8, 2019

Josh Axe state about St John’s
“For severe depression, take about 900 milligrams of St. John’s wort by mouth daily for eight to 12 weeks (with doctor approval).”

Why 12 weeks? Is there a long term side effect or toxicity too be mindful of?

    David Tomen
    September 9, 2019

    Robert, I’m not aware of any time limit on St. John’s wort usage as long as you’re following dosage recommendations. And are aware of side effects and contraindications with prescription drugs and some nootropic supplements.

August 21, 2019

I’ve a lot of years suffering with anhedonia and libido problems.
I’d like to know if there is some nootropic stack that it helps.

    David Tomen
    August 22, 2019

    Demian, I’ve been asked this question several times and the deeper I go into the subject, the more I realize there is no simple solution. Or nootropic stack that will help you deal with anhedonia. Of which low libido is a symptom.

    And this subject is part of ongoing clinical trial too. I’m going to provide an example which I pretty much guarantee will melt your brain. But here goes:

    “… imaging studies have clearly shown that the severity of anhedonia is correlated, in depressed patients, with a deficit of activity of the ventral striatum (reflecting decreased function of the nucleus accumbens, probably as a primary event) and an excess of activity of ventral region of the prefrontal cortex (concerning an increased function of the ventral striatum of the prefrontal cortex and the orbitofrontal cortex, probably as a secondary phenomenon).

    It is not yet possible to prove that the deficits or excesses of activity are primary or secondary, but the analyses of anhedonic nonclinical subjects, nonanhedonic depressed patients, and depressed patients with various levels of anhedonia seems to favor this way of thinking.

    This oversimplified way of assessing the role of two major structures in anhedonia as a pivotal symptom of depression also has to be confronted with the complexity of the concept of anhedonia.

    Indeed, in order to get a pleasurable, hedonic feeling, a large number of steps have to be efficient, such as arousal (being able to globally detect potentially rewarded stimuli), appraisal (having the capacity to detect which specific stimuli are hedonically relevant), and expression of this emotion (being detected).”

    Dopamine is definitely part of the issue. But in different areas of the brain. Along with glutamate, NMDA receptors, opiate receptors, and others.

    The closest I’ve been able to get to dealing with anhedonia is with a post I did awhile back called, “Hacking Motivation with Nootropics”. You can see that post here:

    I suggest experimenting with some of the nootropics listed in the last half of that post. One or two at a time and closely following dosage recommendations. And see if you get any relief of your symptoms.

August 1, 2019

Good afternoon, I am 42 y.o. and I have had a past of MDMA/Ecstasy abuse, and cannabis as well. Lately i had a stressful period and for some time i could sleep only 3-4 hours per night. I am stressed and anxious. I tried 5 HTP, but no results. Melatonin helps.

I tried Phenibut (250mg 3 hours before sleep), and i can sleep as a baby, but i don’t want it as a long term solution of course.

Now i seem to be sleeping good with 900mg of Valerian before sleep, and 1mg of melatonin.

I would like to quit melatonin.

Therefore, based on what i have read here, I am considering to keep taking valerian at night, and take in the morning: St. John’s wort, Rhodiola Rosea, Bacopa Monnieri or L-Theanine.

Which one do you think i should take? I am a bit scared of St. John, but being GabA agonist as Phenibut, i don’t think i should have problems.

Many thanks for any advice.


    David Tomen
    August 2, 2019

    Ivan, St. John’s wort may be a good option for you as long as you follow dosage recommendations. And are NOT using any prescription meds like antidepressants or anti-anxiety medication.

    A gentler source of melatonin is 500 mg L-Tryptophan about 60 mins. before bed. And/or 6 oz. tart cherry juice from concentrate because it’s a natural source of melatonin.

    Melatonin supplement are bad news because they are synthetic. And several studies have shown that what’s in the capsule in not what’s stated on the label. It’s either far less or much more than what is claimed on the label.

    Rhodiola, Bacopa and L-Theanine during the day are also great options for anxiety.

      August 3, 2019

      Dear David, many thanks for your precious advices.

      May i add some details as background: one night i took MDMA pure crystals, way more one is allowed in one night (1 gram, i know, silly me, i was not aware of dosage after years of break), and i was on a binge, the night before i took MDMA pills too. For three nights i could not sleep, i had twitches starting from the back of my neck when in bed (also during the day at the beginning). I had to take some benzoes to sleep, only for a few weeks, even if less than minimum dosage, i hate to become addicted to anything. Then i managed, in months/years to have a quite normal sleep (with help of melatonin). But after 8 years, still yesterday i had some twitches before falling asleep. I think my hyppocampus got damaged somehow. But i know our body is a miracle machine and can heal itself with time, so i am confident.

      With phenibut i fall asleep in no time (i took it only for two weeks). Without phenibut, i need at least 30-90 minutes to fall asleep (with valerian and melatonin).

      I am not taking any prescription meds like antidepressants or anti-anxiety medication. I hate medicines, i only take them if i am really really feeling bad.

      The melatonin i am taking is the best i can find in Italy, pure melatonin, no other ingredients at least this is what they say. But i still want to quit it, so i will try L-Tryptophane at night as you suggested, together with Valerian Root.

      As for the other products to take in the morning, i read here that Rhodiola and Bacopa respectively “influence” and “modulate” serotonin.

      While L-Theanine “increases” serotonin. St.John’s wort “inhibits the reuptake of serotonin” (so i presume increases the amount of serotonin in the brain).

      Based on this, even if i take the smallest dosage (as i always do), don’t i risk to have too much serotonin with L-Tryptophane? Is it better if i use Rhodiola and Bacopa, and avoid L-Theanine and St.John’s wort ? Maybe i would not risk serotonin syndrome, but too much serotonin could have an adverse effect on sleep, or am i wrong?

      A good weekend to you and again thanks for sharing your wisdom.


        David Tomen
        August 4, 2019

        Ivan, the problem with too much serotonin worst case is Serotonin Syndrome which can be fatal. This is not as serious of a problem when using these supplements and NOT using any prescription SSRIs. However …

        Another problem is that too much serotonin depresses dopamine. These two neurotransmitters must be in balance. Use caution in the number of supplements you are taking concurrently that influence the serotonin pathway (which includes melatonin).

        You can counteract the side effects of excess serotonin/depleted dopamine by using something like L-Tyrosine during the day. NOT late afternoon or evening or it will cause insomnia.

        August 5, 2019

        The big question is: how do i know if i have excess of serotonin or dopamine? Are there specific exams that i can do ?

        Or do these values change during the day?

        Because to be honest, i have no idea of what is my serotonin/dopamine ratio.

        David Tomen
        August 5, 2019

        Ivan, there is no accurate or reliable ‘test’ for these types of neurotransmitters. And yes, it can change throughout the day.

        I suggest Googling symptoms of high and low dopamine and then for serotonin. Then watching and listening for signs of these symptoms in your own body. It takes a little practice but you’ll soon become an expert on your own body and brain. And the signals it’s giving you and what it needs.

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