What is St. John’s Wort?
This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. St. John’s Wort (Hypericum perforatum) is a medicinal herb that has been used for centuries for its various therapeutic properties. It is native to Europe and Asia but has also been introduced and naturalized in the United States. This article explores the chemistry, pharmacology, clinical properties, and potential drug interactions associated with St. John’s Wort. Other names include: Amber, Amber Touch-and-Heal, Barbe de Saint-Jean, Chasse-diable, Demon Chaser, Fuga Daemonum, Goatweed, Hardhay, Herbe à la Brûlure, Herbe à Mille Trous, Herbe Aux Fées, Herbe Aux Mille Vertus, Herbe Aux Piqûres, Herbe de Saint Éloi, Herbe de la Saint-Jean, Herbe du Charpentier, Herbe Percée, Hierba de San Juan, Hypereikon, Hyperici Herba, Hypericum perforatum, Klamath Weed, Millepertuis, Millepertuis Perforé, Rosin Rose, Saynt Johannes Wort, SJW, Tipton Weed.
Chemical Composition
The chemical composition of St. John’s Wort has been extensively studied. The primary active constituents include hypericin, hyperforin, and various flavonoids. Hypericin is known for its photosensitive reactions, while hyperforin is primarily responsible for the herb’s antidepressant activity3 8.
Pharmacological Activities
St. John’s Wort exhibits a range of pharmacological activities, including antidepressant, antiviral, and antibacterial effects. These activities support several traditional uses of the herb. The antidepressant effects are particularly well-documented, with hyperforin emerging as a key constituent responsible for this activity3 8.
Clinical Uses of St. John’s Wort
Depression
St. John’s Wort is widely used for the treatment of mild to moderate depression. Clinical studies and meta-analyses have shown that it is as effective as standard selective serotonin reuptake inhibitors (SSRIs) but with fewer side effects9 10. However, its efficacy in severe depression remains unclear, and long-term safety data are limited9.
Pain Management
Recent studies have also explored the potential of St. John’s Wort in managing pain conditions. Preclinical studies indicate that low doses of the herb can relieve acute and chronic pain and augment opioid analgesia. However, clinical research in this area is still scarce5.
Drug Interactions
St. John’s Wort is known to interact with various drugs, primarily through the induction of the cytochrome P450 (CYP) 3A4 enzyme system and the P-glycoprotein drug transporter. These interactions can reduce the efficacy of co-administered medications, including HIV protease inhibitors, immunosuppressants, and hormonal contraceptives1 2 4 6. The constituent hyperforin is likely responsible for CYP3A4 induction, while hypericin may induce P-glycoprotein1 2 4.
Safety and Tolerability
While St. John’s Wort is generally well-tolerated, its potential to induce drug metabolism necessitates caution. Physicians should be aware of these interactions and monitor patients closely when the herb is added, discontinued, or its dosage is changed1 2 10.
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Adverse Effects of St. John’s Wort
Common Adverse Effects
Gastrointestinal symptoms, dizziness, confusion, tiredness, and sedation are frequently reported adverse effects2 9.
Photosensitivity, although rare, is a potential serious adverse effect2.
Gender-Specific Adverse Effects
Women may experience ambient temperature-dependent allodynia, paresthesia, and phototoxic erythrodermia, particularly in sun-exposed areas3.
Drug Interactions
St. John’s Wort can significantly interact with various medications, including warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives, often reducing their efficacy1 4 5 6 10.
These interactions are primarily due to the induction of cytochrome P450 enzymes (CYP3A4, CYP2C9, CYP1A2) and the transport protein P-glycoprotein4 5 6 10.
Serotonin Syndrome
There is a risk of serotonin syndrome when St. John’s Wort is used in combination with selective serotonin reuptake inhibitors (SSRIs) or other serotonergic agents7 8 10.
Reproductive Health
Potential adverse effects on male sexual and reproductive health include reduced libido, delayed ejaculation, erectile dysfunction, and reproductive toxicity (e.g., spermicidal effects, abnormal spermatozoa)7.
Other Adverse Effects
Hair loss has been reported as a possible adverse effect8.
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How has St. John’s Wort Improved Patient Outcomes?
Efficacy in Treating Depression
St. John’s wort is more effective than placebo in treating mild to moderate depression and is comparable to standard antidepressants in terms of efficacy1 4 5 6.
Patients using St. John’s wort experience fewer adverse effects compared to those using standard antidepressants1 5 6.
Quality of Life Improvements
St. John’s wort improves menopause-specific quality of life and reduces sleep problems in perimenopausal women3.
It produces positive shifts in emotional processing, similar to other antidepressants, which may contribute to its antidepressant effects10.
Platelet Reactivity and Cardiovascular Health
St. John’s wort improves platelet response in patients resistant to clopidogrel after percutaneous coronary intervention, indicating potential benefits for cardiovascular health2.
Glucose Tolerance
St. John’s wort enhances glucose tolerance and insulin secretion in healthy subjects taking metformin, suggesting benefits for metabolic health7.
Economic Benefits
St. John’s wort is a cost-effective alternative to standard antidepressants, offering similar clinical benefits with lower costs and fewer adverse effects8.
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St. John’s Wort Mechanisms of Action
Neurotransmitter Uptake Inhibition
St. John’s wort inhibits the synaptosomal uptake of serotonin, dopamine, and noradrenaline with approximately equal affinity, which is similar to the action of some synthetic antidepressants1 4 7.
Hyperforin, a key constituent, inhibits the re-uptake of these neurotransmitters by affecting the sodium gradient rather than acting as a competitive inhibitor at the transmitter binding sites8.
Receptor Interactions
St. John’s wort extract shows significant affinity for adenosine, GABAa, GABAb, and glutamate receptors, and leads to a downregulation of β-adrenergic receptors and an upregulation of serotonin 5-HT2 receptors in the brain1 5.
Hypericin, another active component, has been shown to bind to sigma receptors, which may contribute to its antidepressant effects4 10.
Enzyme Induction
St. John’s wort activates the pregnane X receptor (PXR), leading to the induction of cytochrome P450 (CYP) 3A4, an enzyme involved in the metabolism of many drugs. This can result in increased drug metabolism and potential drug interactions2 6 9.
Neuroendocrine and Immune System Modulation
St. John’s wort affects the hypothalamic-pituitary-adrenal (HPA) axis, reducing stress-induced increases in plasma ACTH and corticosterone levels, and modulating immune responses by reducing inflammatory markers like TNF-alpha3.
Oxidative Defense Mechanisms
The extract enhances antioxidant capacity by increasing the activity of enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the brain, which may protect against oxidative stress associated with depression3.
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Common Complaints Associated with St. John’s Wort Use
Drug Interactions
St. John’s Wort can induce the cytochrome P450 (CYP) 3A4 enzyme system and the P-glycoprotein drug transporter, reducing the efficacy of co-medications such as HIV protease inhibitors, immunosuppressants, and certain antineoplastic agents2 4.
It can impair the efficacy of hormonal contraceptives, leading to irregular bleeding and unwanted pregnancies2 4.
St. John’s Wort can cause serotonin syndrome when combined with selective serotonin-reuptake inhibitors (SSRIs)4.
Adverse Effects
There were no significant differences in adverse events, laboratory values, or tolerability between St. John’s Wort and placebo in a study on climacteric complaints1.
St. John’s Wort has a lower discontinuation/dropout rate compared to standard SSRIs, indicating better tolerability3.
Pharmacokinetic Concerns
St. John’s Wort decreases the blood concentrations of several drugs, including cyclosporine, digoxin, and warfarin, which can lead to serious clinical consequences such as organ rejection and reduced therapeutic efficacy4.
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Disclaimer
The content presented in this blog is generated by Consensus, an AI-powered academic search engine, and is based on publicly available scientific literature. While every effort is made to provide accurate, up-to-date, and well-researched information, the content is intended for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making any decisions regarding medical conditions, treatments, or medications. The AI system’s analysis may not cover all perspectives, emerging research, or individual cases, and it is not a substitute for professional expertise. Neither the blog publisher nor the developers of the AI-powered search engine are responsible for any actions taken based on the information provided in this content. Use of this information is at your own risk. Citations to the original scientific studies are included for reference, but these studies should be reviewed in full and interpreted with the guidance of a healthcare or research professional.
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