How does St. John’s wort work?
The medicinal parts of the St. John’s wort plant include its flowers and, to a lesser extent, its leaves. The main active components are napthodianthrones (e.g., hypericin and pseudohypericin), phloroglucinols (e.g., hyperforin), and flavonoids (e.g., quercetin, kaempferol, and luteolin). It was formerly believed that hypericin was the component of St. John’s wort primarily responsible for its antidepressant action, however, it is now understood that hyperforin, adhyperforin, and several other related compounds are the primary active constituents. These chemicals act on messengers in the nervous system that regulate mood. (8)
St. John’s wort benefits
St John’s wort is believed to increase the activity of brain chemicals such as serotonin, dopamine, gamma aminobutyric acid (GABA), and norepinephrine that play an important part in regulating our mood. (4)St. John’s wort for depression
Oral intake of St. John’s wort extract appears to improve mood and decrease nervousness and fatigue related to depression. In a study of 251 individuals with acute major depression, those who took 900 mg to 1800 mg of St. John’s wort for six weeks experienced a 56.6% decrease in their depression score, compared to a 44.8% decrease in individuals taking pharmaceutical antidepressants. St. John’s wort was also found to be better tolerated. (13) Furthermore, a 2016 review of studies evaluated the effectiveness of St. John’s wort in the treatment of Major Depressive Disorder (MDD). The review included 35 previously published studies, including a total of 6993 participants. Researchers determined that St. John’s wort supplementation reduced symptoms of mild to moderate depression more than a placebo and similar to prescription antidepressants. However, the review also noted that there was a lack of research examining the effects of St John’s wort for severe depression, as well as poor reporting of adverse events. (3)St. John’s wort for sleep
St. John’s wort supplementation is often used to improve sleep. While there is little research examining the effects of St. John’s wort on sleep, some evidence suggests that this herb may be beneficial by prolonging the duration of deep sleep, a stage of sleep important for physical and mental recovery. Furthermore, other research suggests that St. John’s wort primarily affects sleep patterns, rather than overall sleep quality. In one study, 12 participants were given either 300 mg of St. John’s wort three times per day or a placebo over a 4-week period. Individuals who supplemented with St. John’s wort increased the time spent in deep sleep compared to the placebo. No differences in sleep onset or sleep continuity were observed. (12)St. John’s wort for anxiety
While much of the research examining the use of St. John’s wort has been conducted in individuals with depression, according to the Anxiety and Depression Association of America, an estimated 50 percent of people with depression also suffer from some form of anxiety disorder. (2) It has therefore been theorized that St. John’s wort may benefit individuals with anxiety due to its effect on the activity of serotonin, dopamine, GABA, and norepinephrine. However, long-term human studies examining the effectiveness of St. John’s wort in managing anxiety are needed. (5)St. John’s wort for menopause symptoms
As a result of declining estradiol levels around menopause, many women experience symptoms such as hot flashes. St. John’s wort has been found to have molecular components similar to those of human hormones, and therefore, it has been suggested as a possible intervention to reduce menopausal symptoms. (1) In a systematic review, researchers evaluated the possible benefits of black cohosh, St. John’s work, chasteberry, vitamins and minerals, or their combination, on menopausal symptoms. The results suggest the combination of black cohosh and St. John’s wort to be more effective at improving menopausal symptoms when compared to placebo. Black cohosh alone and a combination of St. John’s wort and chasteberry were not found to be superior to the placebo. (9)St. John’s wort side effects
St. John’s wort is generally considered safe when it is taken orally in appropriate doses. However, possible side effects include:- Difficulty sleeping
- Dizziness
- Dry mouth
- Headache
- Irritability
- Nervousness
- Restlessness
- Skin rash or tingling
- Tiredness
- Upset stomach or diarrhea (6)
- Antidepressants
- Birth control pills
- Cyclosporine, which prevents the body from rejecting transplanted organs
- Digoxin, a medication used to treat heart failure
- Some HIV drugs, including Indinavir
- Some cancer medications, including Irinotecan
- Warfarin, a blood thinner (10)
The bottom line
St. John’s wort has been studied most extensively as a treatment for depression. Most studies demonstrated that St. John’s wort may help address mild-to-moderate depression, with fewer side effects than most other prescription antidepressants. As always, be sure to speak to your integrative healthcare provider to identify potential interactions and to determine if a St. John’s wort supplement is right for you.References
- Abdali K, Khajehei M, Tabatabaee HR. Effect of St John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause. 2010;17(2):326-331. doi:10.1097/gme.0b013e3181b8e02d
- Anxiety and Depression Association of America. (n.d.). Facts & Statistics. Retrieved from https://adaa.org/about-adaa/press-room/facts-statistics
- Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1):148. Published 2016 Sep 2. doi:10.1186/s13643-016-0325-2
- Butterweck V. Mechanism of action of St John’s wort in depression : what is known?. CNS Drugs. 2003;17(8):539-562. doi:10.2165/00023210-200317080-0000
- Caccia S, Gobbi M. St. John’s wort components and the brain: uptake, concentrations reached and the mechanisms underlying pharmacological effects. Curr Drug Metab. 2009;10(9):1055-1065. doi:10.2174/138920009790711878
- Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John’s wort (Hypericum perforatum L.). Eur J Clin Pharmacol. 1998;54(8):589-594. doi:10.1007/s002280050519
- Final report on the safety assessment of Hypericum perforatum extract and Hypericum perforatum oil. Int J Toxicol. 2001;20 Suppl 2:31-39. doi:10.1080/10915810160233749
- Kim HL, Streltzer J, Goebert D. St. John’s wort for depression: a meta-analysis of well-defined clinical trials. J Nerv Ment Dis. 1999;187(9):532-538. doi:10.1097/00005053-199909000-00002
- Laakmann E, Grajecki D, Doege K, zu Eulenburg C, Buhling KJ. Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic review. Gynecol Endocrinol. 2012;28(9):703-709. doi:10.3109/09513590.2011.650772
- National Center for Complementary and Integrative Health. (2016). St. John’s Wort. Retrieved from https://www.nccih.nih.gov/health/st-johns-wort
- National Center for Complementary and Integrative Health. (2017). St. John’s Wort and Depression: In Depth. Retrieved from https://www.nccih.nih.gov/health/st-johns-wort-and-depression-in-depth
- Schulz H, Jobert M. Effects of hypericum extract on the sleep EEG in older volunteers. J Geriatr Psychiatry Neurol. 1994;7 Suppl 1:S39-S43. doi:10.1177/089198879400700111
- Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John’s wort): randomised controlled double blind non-inferiority trial versus paroxetine . BMJ. 2005;330(7490):503. doi:10.1136/bmj.38356.655266.82
