The belief that a product that is natural is also safe is a common misconception among users of herbal remedies1. In reality, herbal remedies have the same potential to elicit adverse effects as prescription drugs either directly or indirectly through interactions with other herbs and/or synthetic drugs2. In Canada, approximately 71% of people have reported using some type of herbal therapy including homeopathic drugs, herbal remedies, vitamin supplements and minerals5. Of those only about 12% report having experienced adverse effects from herbal remedy use5. However, less than half of all users of herbal remedies in Canada report adverse reactions5. Other risks are associated with the use of herbal remedies including contamination with heavy metals or over concentrating the pill with the active ingredient during manufacturing, false claims which delay consumers from seeking medical treatment and absent warning labels regarding adverse effects and interactions5. The latter risk is especially true for a product sold in Canada which has risen in popularity across North America and Europe in recent years for the treatment of mild to moderate depression1,2. Specifically, in Canada it is among the top ten most popular herbal remedies6. This product is St. John’s Wort, also known as Hypericum perforatum, an antidepressant that interacts with countless prescription drugs. This reflection will introduce and briefly discuss the risks associated with the use of Hypericum perforatum or St. John’s Wort as it is more commonly known.
St. John’s Wort is a plant of the family Hypericaceae whose extract is used in herbal remedies to treat mild to moderate depression1,2. It has also been used in the treatment of anxiety, sleep disorders, obsessive compulsive disorder, seasonal depression, cancer, gastritis, burns, cuts and abrasions, kidney disease, scabies, hemorrhoids and hypothyroidism1,2. The main ingredients are hypericin and pseudohypericin as well as hyperforin and adhyperforin1. All four ingredients are similar in structure and exert the main pharmacological effects of the herbal medicine1. However, hypericin is thought to be the active ingredient in the treatment of depression1. The effective dose is 900 mg per day taken as three separate doses (ie. 300 mg taken three times daily) with 0.2-0.3% hypericin in the formula1,2. Animal studies and clinical trials have found St. John’s Wort to be highly efficacious in the treatment of mild to moderate depression when used without any other drugs or herbal medicines1,2. This is because it inhibits the reuptake of serotonin, noradrenaline, dompamine, glutamate and gamma-aminobutyric acid which are neurotransmitters that play a role in mood regulation1. A few clinical studies have found it to be as effective at treating mild to moderate depression as tricyclic antidepressants as well as imipramine (both prescription drugs)1,2. In addition, the herbal remedy has few adverse effects, again when used by itself, and in some cases has been found to have less adverse effects than similar prescription antidepressants; a meta-analysis of 23 studies of clinical trials completed by Russo et al. (2013) found 19.8% reported effects in St. John’s Wort users compared to 35.9% reported effects in users of prescribed antidepressants1,2. The adverse effects that it does have are relatively mild and include mild gastrointestinal irritation, lethargy, allergic reactions, dizziness, nausea, rash and restlessness1. The more serious side effects, photosensitivity and manic episodes, are rare and the latter occurs only in predisposed patients1,2.
Despite a lack of direct adverse effects, St. John’s Wort is still an herbal medicine to be concerned about because of its ability to interact with several prescription drugs. Among the prescription drugs St. John’s Wort can interact with are, central nervous system drugs, bronchodilators, cardiovascular drugs, calcium channel blockers, cardiac inotropic drugs, hypocholesterolaemic drugs, gastrointestinal drugs, oral contraceptives, anti-inflammatories, anti-microbials, antineoplastics, immunosuppresants, oral hypoglycaemic and drugs used in the treatment of HIV1,3. Its ability to interact with these drugs is due to alternate mechanisms of action (MOA) which do not play a role in the treatment of depression. First, St. John’s Wort is a potent activator of CYP enzymes that are involved in the metabolism of drugs1,2. Through this mechanism it can decrease the plasma concentration of prescription drugs taken concurrently with St John’s Wort1,2. Second, it also intensifies the activity of P-glycoprotein (P-gp) which is an adenosine triphosphate-dependent drug transporter that is located throughout the body and plays an active role in drug excretion1. Most prescription drugs are metabolized and excreted using CYP enzymes and P-gp transporters, respectively1. Therefore, the joint use of St. John’s Wort with prescriptions drugs that fall under the category listed above can result in the prescription drugs losing their effectiveness via increased metabolism and clearance1,2. Lastly, in the case of CNS drugs, St. John’s Wort may act synergistically resulting in serotonin syndrome which, in worst-case, can result in a coma1.
Subsequently, the concern with St. John’s Wort is its ability to interact with several prescribed drugs. Often, it is not taken alone but is taken in combination with other prescription medicines1. Its use is under-reported to medical professionals both because they do not ask for the information and because the public does not perceive the use of this herbal medicine as a risk to their health1,2. Furthermore, natural health products (NHP) such as St. John’s Wort are not as rigorously regulated as prescription medicines in Canada which can lead to their misuse and the occurrence of adverse effects which go un-reported4,5. Future reflections will explore in greater depth the interaction of St. John’s Wort with clinical drugs in order to characterize the hazard, the estimated exposure of the population to St. John’s Wort, potential at-risk populations, the perception of risk that the Canadian population has towards this drugs, the estimated risk, the current regulations of NHP and their shortfalls and potential solutions to ensure that the risk of NHPs, particularly, St. John’s Wort are being explored, assessed and evaluated, and made public.
Please note: all references are hyperlinked in-text. However, they are also provided below for your convenience
- Russo E., Scicchitano F., Whalley B.J., Mazzitello C., Ciriaco M., Esposito S., PAtane M., Upton R., Pugliese M., Chimirri S., Mammi M., Palleria C. (2013). Hypericum perforatum: Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions. Phytother. Res. DOI: 10.1002/ptr. 5050
- Ernst E. (2002). The Risk-Benefit Profile of Commonly Used Herbal Therapies: Gingko, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto and Kava. Complementary and Alternative Medicine Series. 136 (1): 42 – 53
- University of Maryland Medical Center. (2011). Possible Interactions with: St. John’s Wort. University of Maryland School of Medicine: http://umm.edu/health/medical/altmed/herb-interaction/possible-interactions-with-st-johns-wort
- Health Canada. (2012). Drugs and Health Products: A new approach to natural health products. Government of Canada. http://www.hc-sc.gc.ca/dhp-mps/prodnatur/nhp-new-nouvelle-psn-eng.php
- Health Canada (2012). Drugs and Health Products: About Natural Health Products. Government of Canada. http://www.hc-sc.gc.ca/dhp-mps/prodnatur/about-apropos/cons-eng.php
- World Health Organization. (2002). Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 82