Stress Relief [Discontinued] by BIOVEA

There is insufficient reliable information available about the effectiveness of cereus.

(Read more about CEREUS)

POSSIBLY EFFECTIVE

• Anxiety. Oral kava seems to improve anxiety when taken for at least 5 weeks. Details: Most clinical research shows that kava extracts 150-400 mg, standardized to 70% kavalactones, daily are superior to placebo for relieving symptoms of non-psychotic anxiety (2094,2095,11372,18315,18316,18317,18320,98980), and are possibly comparable to buspirone 10 mg or low-dose benzodiazepines such as oxazepam 30 mg (18314). However, kava may not be effective for improving subthreshold anxiety. A meta-analysis of 3 small clinical studies in patients with subthreshold anxiety shows that taking kava does not improve anxiety symptoms when compared with placebo (110711). Overall, kava's effects appear to be dose-dependent and duration-dependent. One meta-analysis suggests that taking more than 200 mg kavalactones daily tends to be more beneficial for anxiety than taking less than 200 mg kavalactones daily (98980). Some clinical research also suggests that kava extract must be taken for at least 5 weeks to provide a benefit (2094,15046,18314,98980), while single-dose treatments may not be beneficial for acute anxiety (18319). Most studies have used a specific standardized extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals) 150-300 mg daily. Another specific kava extract (LI 150, Lichtwer Pharma) 400 mg daily has also been used (18314,98980). Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) conclude that there is evidence supporting the use of kava for acute or short-term management of general anxiety symptoms but that only products standardized to a sufficient level of kavalactones should be recommended (110318).

POSSIBLY INEFFECTIVE

• Generalized anxiety disorder (GAD). Oral kava doesn't seem to be effective for treating GAD. Details: A meta-analysis of 3 small, low-quality clinical studies in adults with GAD shows that kava extract standardized to 70% kavalactones, providing 140-280 mg kavalactones daily, is no more effective than placebo when used for 4-8 weeks (15130). Additionally, a more recent meta-analysis of 3 moderate-sized clinical trials in patients diagnosed with GAD shows that taking kava does not reduce anxiety when compared with placebo or conventional therapy (110711). While a small clinical trial in adults with GAD shows that taking kava rootstock extract, standardized to provide 120-240 mg of kavalactones daily, for 6 weeks reduces clinician rated anxiety scores when compared with placebo (29663), a large, multi-center clinical trial from the same research group shows that taking kava root extract standardized to 120 mg of kavalactones twice daily for 16 weeks does not reduce anxiety scores when compared with placebo in adults diagnosed with GAD (102086). Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommends against the use of kava rootstock extracts (standardized to 60-250 mg kavalactones) as either monotherapy or adjunctive therapy in patients with GAD (110318). This recommendation against kava for GAD is based on high quality evidence from a meta-analysis and two additional clinical trials, along with a meta-review of two meta-analyses on the use of kava for GAD (110318,112133).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Benzodiazepine withdrawal. It is unclear if oral kava is beneficial for reducing benzodiazepine withdrawal symptoms. Details: One small clinical study in patients with non-psychotic anxiety shows that titrating a specific kava extract (WS1490, Dr. Willmar Schwabe Pharmaceuticals) up to 300 mg daily over one week while tapering the benzodiazepine over 2 weeks is no more effective than placebo for decreasing benzodiazepine withdrawal symptoms (7325).
• Cancer. It is unclear if oral kava is beneficial in patients with cancer. Details: Epidemiological evidence has found that increasing kava consumption is associated with a lower incidence of cancer (8175).
• Epilepsy. Although there is interest in using oral kava for epilepsy, there is insufficient reliable information about the clinical effects of kava for this condition.
• Insomnia. It is unclear if oral kava is beneficial in patients with insomnia. Details: One small clinical study shows that taking a specific kava extract (WS1490, Dr. Willmar Schwabe Pharmaceuticals) 200 mg standardized to 70% kavalactones daily for 4 weeks reduces sleep disturbances associated with non-psychotic anxiety disorders (18321). However, another internet-based clinical trial in patients with self-reported insomnia associated with anxiety suggests that taking kava in a dose equivalent to 100 mg kavalactones three times daily for 4 weeks does not improve sleep when compared with placebo (15046).
• Menopausal symptoms. It is unclear if oral kava is beneficial for menopausal symptoms. Details: One small clinical study shows that taking kava 100-200 mg standardized to contain 55% kavaina daily for 3 months reduces depression, anxiety, and hot flashes when compared to baseline in perimenopausal patients. However, the changes in depression and hot flashes were not better when compared with the control group that took calcium (18318).
• Myalgia. Although there is interest in using oral kava for myalgia, there is insufficient reliable information about the clinical effects of kava for this condition.
• Premenstrual syndrome (PMS). Although there is interest in using oral kava for PMS, there is insufficient reliable information about the clinical effects of kava for this condition.
• Sexual arousal. Although there is interest in using oral kava for sexual arousal, there is insufficient reliable information about the clinical effects of kava for this condition.
• Stress. It is unclear if oral kava reduces reactivity to experimental stress. Details: A small study in healthy volunteers shows that taking a single dose of kava (LI 150, Lichtwer Pharma) 120 mg orally might reduce the physiological changes associated with mentally stressful tasks when compared to baseline (9893). More evidence is needed to rate kava for these uses.

(Read more about KAVA)

POSSIBLY INEFFECTIVE

• Smoking cessation. Some small clinical studies have evaluated the use of lobeline, a constituent of lobelia, for smoking cessation and stopping use of smokeless tobacco over a 48-hour period. These studies show inconsistent effects of lobelia on tobacco use, with many finding no benefit. The validity of these findings is limited by low study quality and the short duration of use (16413,16414,59987). There is insufficient reliable information available about the effectiveness of lobelia for its other uses.

(Read more about LOBELIA)

There is insufficient reliable information available about the effectiveness of pulsatilla.

(Read more about PULSATILLA)

LIKELY EFFECTIVE

• Depression. Specific formulations of oral St. John's wort are effective for mild or moderate major depressive disorder. St. John's wort may also cause fewer side effects than certain conventional antidepressants. Details: Moderate quality meta-analyses and individual clinical trials show that St. John's wort extracts are more effective than placebo (76057,76140,76143,76271,89669,104036), and likely as effective as low-dose tricyclic antidepressants (6434,76143), tetracyclic antidepressants (76174), and selective serotonin reuptake inhibitors (SSRIs) (76143,76144,96551), including fluoxetine (Prozac) (3550,4897), sertraline (Zoloft) (6400), and paroxetine (Paxil) (13021) for treating depression. However, some of these studies have been critiqued for using lower doses of SSRIs than typical dosing in comparative studies (104037). St. John's wort also seems to have better tolerability and less gastrointestinal, neurologic, and sexual adverse effects than certain conventional antidepressants (104036). Taking St. John's wort extract improves mood and decreases anxiety, somatic symptoms, and insomnia related to mild to severe major depression (3550,4897,6400,13021,13157,76143,104036). Short-term response rates to St. John's wort appear to be between 65% and 100%; however, long-term, the response rates appear to range from 60% to 69% (13156). Most studies have evaluated St. John's wort in adults; however, there is also some evidence that taking St. John's wort 300-1800 mg daily might be effective for depression in children less than 17 years old (4538,10844,76110). There is some concern that St. John's wort may not be effective for severe major depressive disorder necessitating psychiatric care. Two studies in psychiatric care settings showed no benefit of using St. John's wort (5096,10843). Clinical guidelines from the American College of Physicians state that St. John's wort may be as effective and better tolerated than conventional antidepressants for mild to moderate depression (104037). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that St. John's wort is recommended as monotherapy for mild to moderate forms of major depressive disorder (110318). There is no guarantee that people living in the United States can obtain St. John's wort preparations of similar potency and effectiveness as those used in clinical research (104037). The CANMAT Taskforce recommendation is for specific formulations of 3:1 to 7:1 extracts, standardized to approximately 0.2-0.3% hypericin and/or 5-6% hyperforin, in single or divided doses of 600 mg to 1800 mg daily (110318). Most studies have used St. John's wort extracts standardized to hypericin content, usually 0.3%, but extracts standardized to 1% to 4% hyperforin also seem to be effective. Extracts containing hypericin 0.2% to 0.3%, including LI 160 (Lichtwer Pharma) and Remotiv (Zeller) have most often been studied in doses of 300 mg three times daily for up to 6 weeks, or 250 mg twice daily for up to 6 weeks. Extracts containing 3% to 6% hyperforin, including Movana (Pharmaton) and WS 5570 (Schwabe Pharmaceuticals) have most often been studied in doses of 300-600 mg three times daily for 6-26 weeks (761,4538,4630,104036).

POSSIBLY EFFECTIVE

• Menopausal symptoms. Oral St. John's wort seems to be beneficial for patients with menopausal symptoms. Details: Most clinical research shows that taking St. John's wort as a single supplement can reduce menopausal symptoms. A meta-analysis of small clinical trials in menopausal adults shows that taking St. John's wort up to 900 mg daily for up to 16 weeks, alone or in combination with other herbs, reduces frequency and severity of hot flashes when compared with placebo (95510). Some research also suggests that St. John's wort might improve quality of life and psychological symptoms when compared with placebo (76043,76146,89666,95510). St. John's wort has also shown benefit when used in combination with black cohosh (Remifemin Plus, Schaper & Brummer GmbH & Co. KG; Gynoplus, Jin-Yang Pharm; Feramin Q, Dongkook Pharm) (15037,15893,35853,95510), and with Vitex agnus-castus (41482).
• Somatic symptom disorder. Oral St. John's wort seems to be beneficial for patients with somatoform disorder. Details: Two clinical trials in patients with somatoform disorders shows that taking a specific standardized St. John's wort extract (LI 160, Lichtwer Pharma) 600 mg daily seems to reduce symptoms of somatization disorder by 45% after 6 weeks of treatment when compared with placebo (9476,76089).

POSSIBLY INEFFECTIVE

• Burning mouth syndrome. Oral St. John's wort does not appear to reduce pain from burning mouth syndrome. Details: A small clinical study in patients with burning mouth syndrome shows that taking St. John's wort 300 mg (standardized to hypericin 0.3% and hyperforin 3.0%) three times daily for 12 weeks does not alleviate pain when compared to placebo (76133).
• Hepatitis C. St. John's wort contains hypericin. Synthetic hypericin has been studied and shown to be ineffective as an oral drug for hepatitis C. Details: A small clinical study in patients with chronic hepatitis C virus (HCV) infection shows that giving synthetic hypericin 0.05-0.1 mg/kg orally daily does not seem to be effective for reducing viral load and may be unsafe due to the risk for phototoxic reactions (4631).
• HIV/AIDS. St. John's wort contains hypericin. Synthetic hypericin has been studied and shown to be ineffective as an oral and intravenous drug for HIV. Details: A small clinical study in adults infected with HIV shows that giving synthetic hypericin 0.25-0.5 mg/kg, either intravenously 2-3 times weekly or orally every day, as an antiretroviral agent does not seem to be effective and may be unsafe due to the risk for phototoxic reactions, which occurred in about 50% of patients (206).
• Irritable bowel syndrome (IBS). Oral St. John's wort does not seem to improve symptoms in patients with IBS. Details: A small clinical study shows that taking a specific St. John's wort extract (St. John's Wort Extract Extra Strength, Enzymatic Therapy) 450 mg twice daily is no more effective than placebo for reducing symptoms of IBS after 12 weeks of treatment. In fact, patients taking placebo had improved symptoms compared to St. John's wort (16893).
• Peripheral neuropathy. Oral St. John's wort does not seem to relieve pain in patients with peripheral neuropathy. Details: A small clinical study in diabetic and non-diabetic patients with polyneuropathy shows that taking St. John's wort containing 0.9 mg hypericin orally daily for 5 weeks does not seem to relieve most measures of pain when compared with placebo (7047).
• Social anxiety disorder. Oral St. John's wort does not seem to be beneficial for patients with social anxiety disorder. Details: A small clinical study shows that taking St. John's wort 600-1800 mg daily for 12 weeks does not improve social phobia or social anxiety disorder when compared with placebo (76101).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if topical St. John's wort is beneficial for acne. Details: A small clinical trial in patients with mild to moderate acne treated with photodynamic therapy shows that topical application with 1.5 mL of a St. John's wort 0.5% extract (DR-Light complex; Genicos Co., Ltd, Cheongju, Korea) for 10 minutes for four weekly sessions reduces acne lesion count as effectively as treatment with indole-3-acetic acid (110327).
• Anxiety. Although there is interest in using oral St. John's wort for anxiety, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral St. John's wort is beneficial for improving symptoms in children with ADHD. Details: A small clinical study in children ages 6-17 years with ADHD shows that taking a specific St. John's wort extract standardized to 0.3% hypericin, 300 mg three times daily for 8 weeks, does not improve symptoms such as inattentiveness when compared with placebo (17986).
• Brain tumor. St. John's wort contains hypericin. Synthetic hypericin has been studied as an oral drug for malignant brain tumors, with unclear benefit. Details: A small clinical study in patients with malignant gliomas shows that taking synthetic hypericin 0.05-0.5 mg/kg daily orally for up to 3 months was associated with stable disease in 7 of 42 patients and partial response in 2 of 42 patients (76160). However, it is unclear how these outcomes would compare with historical controls or a prospectively enrolled control group.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral St. John's wort for CFS, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
• Crigler-Najjar syndrome type 2. It is unclear if oral St. John's wort is beneficial for patients with this condition. Details: Crigler-Najjar syndrome type 2 is a rare genetic disorder characterized by the accumulation of bilirubin in the body. One case report of a 24 year-old female with this condition shows that taking St. John's wort (Jarsin LI160, Vifor SA) 300 mg three times daily by mouth for two 8-week periods 18 months apart decreases bilirubin levels by 34%, reduces jaundice, and improves fatigue (95509).
• Fibromyalgia. Although there is interest in using oral St. John's wort for fibromyalgia, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
• Genital herpes. Topical St. John's wort has only been evaluated in combination with copper sulfate; its effect when used alone is unclear. Details: A clinical study in patients with herpes simplex virus 1 (HSV-1) or 2 (HSV-2) shows that applying a single dose of a specific topical product (Dynamiclear, Global Herbal Supplies Pty Ltd), which contains St. John's wort 0.1% and copper sulfate pentahydrate 5%, helps reduce symptoms such as stinging, burning, erythema, and pain. In fact, the combination product appears to reduce erythema, itching, and pain more than applying acyclovir 5% (Zovirax, Glaxo Smith Kline) five times daily for 7 days (76164).
• Herpes labialis (cold sores). Topical St. John's wort has only been evaluated in combination with copper sulfate; its effect when used alone is unclear. Details: A clinical study in patients with herpes simplex virus 1 (HSV-1) or 2 (HSV-2) shows that applying a single dose of a specific topical product (Dynamiclear, Global Herbal Supplies Pty Ltd), which contains St. John's wort 0.1% and copper sulfate pentahydrate 5%, helps reduce symptoms such as stinging, burning, erythema, and pain. In fact, the combination product appears to reduce erythema, itching, and pain more than applying acyclovir 5% (Zovirax, Glaxo Smith Kline) five times daily for 7 days (76164).
• Mastitis. It is unclear if topical St. John's wort is beneficial for granulomatous mastitis. Details: In patients with idiopathic granulomatous mastitis, persistent or intractable skin lesions may remain after treatment with oral steroids and antibiotics. Preliminary clinical research shows that topical application with St. John's wort oil for two minutes twice daily for 6 weeks reduces the severity of skin lesions in patients with persistent lesions following treatment. After treatment, the success rate, based on clearance or remaining mild symptoms, was 94.1% (110326).
• Memory. It is unclear if oral St. John's wort is beneficial for improving memory in healthy people. Details: A small clinical study in healthy adults shows that taking a specific supplement (Remotiv, Zeller) containing St. John's wort 250 mg, standardized to 0.5 mg of hypericin, by mouth as a single dose, seems to improve short-term memory when compared with baseline. In contrast, the same product containing a higher dose of St. John's wort, 500 mg, seems to worsen memory when compared with baseline (100245). The validity of this finding is limited by the lack of a control group.
• Migraine headache. It is unclear if oral St. John's wort is beneficial for reducing migraine headache. Details: A small low quality clinical study in patients with migraines suggests that adding a specific St. John's wort product (Perforan, Godaru) 160 mg three times daily to sodium valproate 400 mg daily might modestly improve migraine intensity, but not migraine frequency, when compared with sodium valproate alone (89667).
• Obsessive-compulsive disorder (OCD). It is unclear if oral St. John's wort is beneficial for reducing OCD symptoms. Details: There is conflicting evidence about the effectiveness of St. John's wort for OCD. A small open-label study suggests that taking a specific St. John's wort extract standardized to 0.3% hypericin (Alterra, Upsher-Smith Laboratories) 450 mg twice daily for 12 weeks might improve symptoms of OCD when compared to baseline (5075). The validity of this finding is limited by the lack of a control group. A small, higher quality clinical study using a different St. John's wort extract (LI 160, Lichtwer Pharma AG) 600-1800 mg daily for 12 weeks shows that it does not improve symptoms of OCD when compared with placebo (14417). However, this study excluded patients with concomitant depression, so it's unclear if St. John's wort might improve OCD symptoms in patients with depression.
• Polycystic ovary syndrome (PCOS). Oral St. John's wort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking three tablets containing St. John's wort, licorice root, Ceylon cinnamon, levant berry, peony, and Tribulus daily for 3 months, in addition to lifestyle changes, improves oligomenorrhea by 33% and quality of life by 30% when compared with lifestyle changes alone in adults with PCOS (97216). It is unclear if these effects are due to St. John's wort, other ingredients, or the combination.
• Premenstrual syndrome (PMS). It is unclear if oral St. John's wort is beneficial for patients with PMS. Details: There is conflicting evidence on the effects of St. John's wort for treating PMS, although most evidence suggests benefit. A small clinical study shows that taking a specific St. John's wort extract standardized to contain 0.18% hypericin and 3.38% hyperforin (LI 160, Lichtwer Pharma AG) 450 mg twice daily for two menstrual cycles reduces physical and behavioral PMS symptoms, but not mood or pain, when compared with placebo (76150). Another clinical study shows that taking St. John's wort extract containing hypericin 1.36 mg daily for two menstrual cycles can reduce symptoms of PMS, including anxiety, depression, forgetfulness, crying, headache, and fatigue, when compared with placebo (76159). However, one clinical study shows that taking St. John's wort 600 mg (standardized to contain 1.8 mg of hypericin) does not reduce anxiety or other PMS symptoms when compared with placebo (76104). The conflicting results may be due to differences in St. John's wort formulations and dosages.
• Psoriasis. It is unclear if topical St. John's wort improves symptoms in patients with plaque psoriasis. Details: A small clinical study in patients with mild or moderate plaque psoriasis shows that applying an ointment containing St. John's wort extract 5% twice daily to one side of the body for 4 weeks modestly decreases the severity, thickness, and degree of erythema of psoriasis plaques when compared with applying placebo ointment to the other side of the body (95940).
• Seasonal affective disorder (SAD). It is unclear if oral St. John's wort is beneficial for patients with SAD. Details: Preliminary clinical research shows that St. John's wort extract improves symptoms associated with SAD, including anxiety, decreased libido, and sleep disturbances, when compared with baseline. It may be beneficial when used alone or in combination with light therapy (9686,76175). However, the validity of these findings is limited by the lack of a comparator group.
• Scleroderma. Topical St. John's wort has only been evaluated in combination with neem oil; its effect when used alone is unclear. Details: A small observational study in patients with systemic sclerosis has found that topical application of a specific cream (Holoil, RI.MOS. SRL) containing St. John's wort and neem oil is associated with improved healing, decreased pain, and reduced need for surgical interventions and antibiotics when compared with a control group (102867). It is unknown if these effects are due to St. John's wort, neem, or the combination. Additionally, the validity of these results is limited by a lack of randomization, blinding, and placebo-control.
• Smoking cessation. It is unclear if oral St. John's wort is beneficial for patients trying to quit smoking. Details: A small clinical study in cigarette smokers shows that taking a specific St. John's wort extract (LI-160, Lichtwer Pharma US) 300 mg once or twice daily, starting 1 week before and continuing for 3 months after quitting smoking, is associated with a continuous abstinence rate of 18% at 3 months and 0% at 12 months, suggesting a lack of benefit (14481).
• Wound healing. Topical St. John's wort seems to improve wound healing and wound-related pain for certain types of surgery. Details: A clinical study in patients who have had a Cesarean section shows that applying ointment containing St. John's wort extract 20% three times a day for 16 days improves wound healing and reduces scar formation when compared with placebo ointment (17225). Preliminary clinical research in patients who have had impacted third molars removed shows that using a mouthwash, prepared by macerating the above ground parts of St. John's wort in virgin olive oil, for 60 days is as effective as chlorhexidine gluconate plus benzydamine hydrochloride mouthwash for improving periodontal healing, and reducing swelling, pain, and infectious complications. However, it was also as effective as plain virgin olive oil, suggesting that St. John's wort did not provide additional benefit. 15 mL of each mouthwash was swished for 30 seconds 3 times daily for 7 days (104957). St. John's wort has also been evaluated in combination with other ingredients. A moderate-sized clinical study in adults with dehisced post-surgical wounds shows that applying a specific aerosol product (1PWD, Kerecis AG) containing St. John's wort and neem oil to wounds during dressing changes does not improve wound healing scores at day 28 but may reduce pain scores when compared with silver-based dressings (alginates or polyurethane foam) (111592). However, this study may have been inadequately powered to detect a difference between groups. It is also unclear if these effects are due to St. John's wort, neem oil, or the combination.
• Tinnitus. St. John's wort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in adults with tinnitus shows that taking St. John's wort 600 mg and ginkgo biloba daily for 12 weeks does not suppress tinnitus or improve tinnitus-related handicap when compared with ginkgo biloba monotherapy (111513). More evidence is needed to rate St. John's wort for these uses.

(Read more about ST. JOHN'S WORT)

POSSIBLY SAFE ...when the flower or stem is used orally for non-cardiac conditions (12). Although it contains cactine, which may have a digitalis-like effect, there are no reports of human toxicity (12).

POSSIBLY UNSAFE ...when used orally to self-medicate for cardiac conditions. There is insufficient reliable information available about the safety of cereus for its other uses.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CEREUS)

POSSIBLY SAFE ...when used orally, short-term. Kava extracts have been used safely in clinical trials under medical supervision for up to 6 months (2093,2094,2095,4032,7325,15046,15130,18314,18316,18318)(18320,29663,29671,98980,102086,112642). Historically, there has been some concern that kava preparations could induce hepatotoxicity and liver failure in patients taking relatively normal doses, short-term. At least 100 cases of liver toxicity following kava use have been reported. Although liver toxicity is more frequently associated with prolonged use of very high doses (6401,57346), in some cases the use of kava for as little as 1-3 months has been associated with the need for liver transplants, and even death (390,7024,7068,7086,7096,17086,57252)(57254,57297). However, some experts question the clinical validity of several of these cases (11369,11371).

PREGNANCY: POSSIBLY UNSAFE
when used orally. There is some concern that pyrone constituents in kava can cause loss of uterine tone (19); avoid using.

LACTATION: POSSIBLY UNSAFE
when used orally. There is concern that the toxic pyrone constituents of kava can pass into breast milk (19); avoid using.

(Read more about KAVA)

LIKELY UNSAFE ...when used orally (3,11). Lobelia leaf can be toxic in doses of 600-1000 mg; 4000 mg of the leaf may be fatal (18). There is insufficient reliable information available about the safety of lobelia when used topically.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally due to its emetic effects (4,12). There is insufficient reliable information available about the safety of lobelia when used topically during pregnancy and lactation.

(Read more about LOBELIA)

LIKELY UNSAFE ...when fresh above ground parts are used orally or topically; pulsatilla is a severe local irritant (4). There is insufficient reliable information available about the safety of the use of dried pulsatilla.

PREGNANCY: LIKELY UNSAFE
when used orally. The fresh or dried above ground parts are contraindicated due to abortifacient and teratogenic effects (2,4). ...when the fresh above ground parts are used topically. There is insufficient reliable information available about the safety of topical dried pulsatilla during pregnancy.

LACTATION: LIKELY UNSAFE
when the fresh above ground parts are used for oral or topical use (19). There is insufficient reliable information available about the safety of dried pulsatilla during breast-feeding.

(Read more about PULSATILLA)

LIKELY SAFE ...when used orally and appropriately. St. John's wort extracts in doses up to 900 mg daily seem to be safe when used for up to 12 weeks (3547,3550,4835,5096,6400,6434,7047,13021,13156,13157)(14417,76143,76144,89666,89669,95510). Some evidence also shows that St. John's wort can be safely used for over one year (13156,13157,76140), and may have better tolerability than selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) (4897,76153,76143,104036).

POSSIBLY SAFE ...when used topically and appropriately. St. John's wort 0.5% extract seems to be safe when used once weekly for 4 weeks (110327). St. John's wort oil has been used with apparent safely twice daily for 6 weeks (110326). However, topical use of St. John's wort can cause photodermatitis with sun exposure (110318).

POSSIBLY UNSAFE ...when used orally in large doses. St. John's wort extract can be unsafe due to the risk of severe phototoxic skin reactions. Taking 2-4 grams of St. John's wort extract (containing hypericin 5-10 mg) daily appears to increase the risk of photosensitivity (758,4631,7808).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Preliminary population research has found that taking St. John's wort while pregnant is associated with offspring that develop neural tube, urinary, and cardiovascular malformations. Subgroup analyses suggest that these risks may be higher when taking St. John's wort during the first trimester when compared with the second or third trimester. However, more research is needed to confirm these findings (106052). Animal-model research also shows that constituents of St. John's wort might have teratogenic effects (9687,15122). Until more is known, St. John's wort should not be taken during pregnancy.

LACTATION: POSSIBLY UNSAFE
when used orally. Nursing infants of mothers who take St. John's wort have a greater chance of experiencing colic, drowsiness, and lethargy (1377,15122,22418); avoid using.

CHILDREN: POSSIBLY SAFE
when used orally, and appropriately, short-term. St. John's wort extracts in doses up to 300 mg three times daily seem to be safe when used for up to 8 weeks in children aged 6-17 years (4538,17986,76110).

(Read more about ST. JOHN'S WORT)

(Read more about CEREUS)

ALCOHOL (ETHANOL) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = A Combining kava with alcohol may increase the risk of sedation and/or hepatotoxicity.  Details Kava has CNS depressant effects (11373,18316). Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression (2093,2098). Additionally, kava has been associated with over 100 cases of hepatotoxicity. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs (7024,7068,7086,7096,17086,57346). Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that alcohol not be used with kava (110318).

CNS DEPRESSANTS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = A Combining kava with CNS depressants can have additive sedative effects.  Details Kava has CNS depressant effects (11373,18316). Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression (2093,2098). Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that CNS depressants, including alcohol and benzodiazepines, not be used with kava (110318).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B It is unclear if kava inhibits CYP1A2; research is conflicting.  Details Although in vitro research and a case report suggest that kava inhibits CYP1A2 (8743,12479,88593), more robust clinical evidence shows that kava has no effect on CYP1A2. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP1A2 activity (13536,98979).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, kava might increase levels of CYP2C19 substrates.  Details In vitro research shows that kava significantly inhibits CYP2C19 enzymes (8743,12479). This effect has not yet been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, kava might increase levels of CYP2C9 substrates.  Details In vitro research shows that kava significantly inhibits CYP2C9 enzymes (8743,12479). This effect has not yet been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B It is unclear if kava inhibits CYP1A2; research is conflicting.  Details In vitro research shows that kava extract significantly inhibits CYP2D6 (8743,12479). However, clinical research shows that kava does not affect the metabolism of CYP2D6 substrates in humans (13536,16848,98979).

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Kava might increase levels of CYP2E1 substrates.  Details In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days inhibited the metabolism of CYP2E1 substrates (13536).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B It is unclear if kava inhibits CYP3AA; research is conflicting.  Details Although in vitro research suggests that kava inhibits CYP3A4 (8743,12479), more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity (13536,98979).

HALOPERIDOL (Haldol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Combining kava and haloperidol might increase the risk of cardiovascular adverse effects and hypoxia.  Details Atrial flutter and hypoxia has been reported for a patient who received intramuscular injections of haloperidol and lorazepam after using kava orally. The side effects were attributed to kava-induced inhibition of CYP2D6, but might also have been related to additive adverse effects with the concomitant use of haloperidol, lorazepam, and kava (88593).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.  Details Kava has been linked with over 100 cases of hepatotoxicity. Most cases occur with excessive and prolonged use. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs (7024,7068,7086,7096,17086,57346).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.  Details In vitro research shows that kava can inhibit P-gp efflux (15131). However, a clinical study in healthy volunteers shows that taking kava standardized to provide 225 mg kavalactones daily for 14 days does not affect the pharmacokinetics of digoxin, a P-gp substrate (15132,98979). It is possible that the use of other P-gp substrates or higher doses of kava might still inhibit P-gp.

ROPINIROLE (Requip) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Taking kava with ropinirole might increase the risk for dopaminergic toxicity.  Details A case of visual hallucinations and paranoid delusions has been reported for a patient who used kava in combination with ropinirole. The adverse effects were attributed to kava-induced inhibition of CYP1A2, which may have reduced the metabolism of ropinirole, resulting in excessive dopaminergic stimulation (88593).

(Read more about KAVA)

(Read more about LOBELIA)

(Read more about PULSATILLA)

ALPRAZOLAM (Xanax) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B St. John's wort increases the clearance of alprazolam and decreases its effects.  Details Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours (10830).

AMBRISENTAN (Letairis) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Probable •  Level of Evidence = B St. John's wort may increase the clearance of ambristentan and decrease its effects.  Details Clinical research in healthy volunteers shows that taking St. John's wort 900 mg daily decreases the area under the concentration-time curve of ambrisentan 5 mg by 17% to 26%. Ambrisentan clearance was increased by 20% to 35% depending on CYP2C19 genotype. However, these small changes are unlikely to be clinically significant (99511).

AMINOLEVULINIC ACID Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort might have additive phototoxic effects with aminolevulinic acid.  Details Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort (9474).

BOCEPREVIR (Victrelis) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B St. John's wort might decrease the levels and clinical effects of boceprevir.  Details Boceprevir increases the maximum concentration and concentration at 8 hours of the St. John's wort constituent, hypericin, by approximately 30%. However, St. John's wort does not significantly change the area under the concentration-time curve or maximum plasma concentration of boceprevir 800 mg three times daily in healthy adults (95507,96552).

BUPROPION (Wellbutrin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort might reduce the levels and effects of bupropion.  Details Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort (89662).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B St. John's wort might increase the levels and effects of clopidogrel.  Details Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity (13038,89671,96552). Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D St. John's wort might decrease the levels and clinical effects of clozapine.  Details A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort (96552).

CONTRACEPTIVE DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.  Details Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy (11886,11887,13099). Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract (9880). St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives (1292,7809,9204).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of cyclosporine.  Details Concomitant use can decrease plasma cyclosporine levels by 30% to 70% (1234,4826,4831,4834,7808,9596,10628,96552). Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection (1234,1293,1301,6112,6435,7808,9596). This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day (6435,10628). Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels (1234,4513,4826,4831,4834). St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance (1293,1340,9204,9596).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.  Details Clinical research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4 (9204,10848,76163).

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.  Details Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20% (89662).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP2C19 substrates.  Details Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces CYP2C19 and increases metabolism of mephenytoin (Mesantoin). In patients with wild-type 2C19 (2C19*1/*1) metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism (17405). Theoretically, St. John's wort might increase metabolism of other CYP2C19 substrates.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP2C9 substrates.  Details There is contradictory research about the effect of St. John's wort on CYP2C9. Some in vitro research shows that St. John's wort induces CYP2C9, but to a lesser extent than CYP3A4 (9204,10848,11889). St. John's wort also induces metabolism of the S-warfarin isomer, which is a CYP2C9 substrate (11890). Other research shows that St. John's wort 300 mg three times daily for 21 days does not significantly affect the pharmacokinetics of a single 400 mg dose of ibuprofen, which is also a CYP2C9 substrate (15546). Until more is known, use St. John's wort cautiously in patients who are taking CYP2C9 substrates.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.  Details St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates (9204,10830,10847,10848,11889,22423,22424,22425,22427,48603). Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more (97171).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of digoxin.  Details St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs (382,6473,7808,7810,9204,96552,97171). St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels (97171).

DOCETAXEL (Taxotere) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of docetaxel.  Details Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (89661).

FENTANYL Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, St. John's wort may reduce the levels and clinical effects of fentanyl.  Details Given that St. John's wort induces cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, it is possible that concomitant use of St. John's wort with fentanyl will reduce plasma levels and analgesic activity of fentanyl (96552). However, some clinical research in healthy adults shows that taking St. John's wort (LI-160, Lichtwer Pharma) 300 mg daily for 21 days does not alter the pharmacokinetics or clinical effects of intravenous fentanyl (102868). It is unclear if these findings can be generalized to oral, intranasal, or transdermal fentanyl.

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B St. John's wort may increase the levels and clinical effects of fexofenadine.  Details A single dose of St. John's wort decreases the clearance of fexofenadine and increases its plasma levels. However, the effect of St. John's wort on plasma levels of fexofenadine seems to be lost if dosing is continued for more than 2 weeks (9685). Patients taking fexofenadine and St. John's wort concurrently should be monitored for possible fexofenadine toxicity.

FINASTERIDE (Proscar, Propecia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D St. John's wort may reduce the levels and clinical effects of finasteride.  Details St. John's wort reduces plasma levels of finasteride in healthy male volunteers due to induction of finasteride metabolism via cytochrome P450 3A4 (CYP3A4). The clinical significance of this interaction is not known (96552).

GLICLAZIDE (Diamicron, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort may reduce the levels and clinical effects of gliclazide.  Details Taking St. John's wort decreases the half-life and increases clearance of gliclazide in healthy people (22431).

HMG-CoA REDUCTASE INHIBITORS ("Statins") Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the effectiveness of atorvastatin, lovastatin, and rosuvastatin. However, it does not seem to affect pravastatin, pitavastatin, or fluvastatin.  Details Concomitant use of St. John's wort can reduce plasma concentrations of the active simvastatin metabolite, simvastatin hydroxy acid, by 28%. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter. This increases simvastatin clearance. It also increases the clearance of atorvastatin (Lipitor), lovastatin (Mevacor), and rosuvastatin (Crestor). St. John's wort does not seem to affect the plasma concentrations of pravastatin (Pravachol), pitavastatin (Livalo) or fluvastatin (Lescol), which are not substrates of CYP3A4 or P-glycoprotein (10627,96552,97171).

IMATINIB (Gleevec) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = A St. John's wort reduces the levels and clinical effects of imatinib.  Details Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib (11888,96552).

INDINAVIR (Crixivan) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort may reduce the levels and clinical effects of indinavir.  Details In healthy volunteers, taking St. John's wort concurrently with indinavir reduces plasma concentrations of indinavir by inducing metabolism via cytochrome P450 3A4 (CYP3A4) (96552). Theoretically, this could result in treatment failure and viral resistance.

IRINOTECAN (Camptosar) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = A St. John's wort reduces the levels and clinical effects of irinotecan.  Details St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve (9206,97171). This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (7092,96552).

IVABRADINE (Corlanor) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort might reduce the levels and clinical effects of ivabradine.  Details Taking St. John's wort 900 mg containing 7.5 mg of hyperforin daily for 14 days with a single dose of ivabradine causes a 62% reduction in plasma levels of ivabradine. This interaction is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, increasing the metabolism of ivabradine (96552,97171).

KETAMINE (Ketalar) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of ketamine.  Details Taking St. John's wort 300 mg three times daily for 14 days can decrease maximum serum levels of ketamine by around 66% and area under the concentration-time curve of ketamine by 58%. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (89663).

MEPHENYTOIN (Mesantoin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of mephenytoin.  Details Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism (17405).

METHADONE (Dolophine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort might reduce the levels and clinical effects of methadone.  Details St. John's wort might decrease the effectiveness of methadone by reducing its blood concentrations. In one report, two out of four patients on methadone maintenance therapy for addiction experienced methadone withdrawal symptoms after taking St. John's wort 900 mg daily for a median of 31 days. There was a median decrease in blood methadone concentration of 47% (range: 19% to 60%) when compared to baseline (22419).

METHYLPHENIDATE (Concerta, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D St. John's wort might reduce the levels and clinical effects of methylphenidate.  Details St. John's wort might decrease the effectiveness of methylphenidate. In one report, an adult male, stabilized on methylphenidate for attention deficit-hyperactivity disorder (ADHD), experienced increased attention problems and ADHD symptoms after taking St. John's wort 600 mg daily for 4 months. ADHD symptoms improved when St. John's wort was discontinued (15544). The mechanism of this interaction is unknown.

NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of NNRTIs.  Details St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter (1290,1340,4837,96552).

OMEPRAZOLE (Prilosec) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of omeprazole.  Details Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers (22440,96552).

OXYCODONE (Oxycontin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of oxycodone.  Details St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity (96552).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.  Details St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action (382,1340,7810,11722).

PHENOBARBITAL (Luminal) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of phenobarbital.  Details St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped (9204).

PHENPROCOUMON (Marcoumar, others) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of phenprocoumon.  Details St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR) (9204).

PHENYTOIN (Dilantin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of phenytoin.  Details St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped (9204).

PHOTOSENSITIZING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.  Details St. John's wort might increase photosensitivity reactions due to its hypericin content (166). However, some clinical research shows that very high doses of St. John's wort are needed to produce phototoxicity in humans (3900,4542,76266).

PROCAINAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might decrease the levels and clinical effects of procainamide.  Details Animal research shows that taking St. John's wort extract increases the bioavailability of procainamide, but does not increase its metabolism (14865). Whether this interaction is clinically significant in humans is not known.

PROTEASE INHIBITORS (PIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of PIs.  Details In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance (1290,7808,96552). St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination (9204).

RESERPINE (Raudixin, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might decrease the effectiveness of reserpine.  Details Animal research shows that St. John's wort can antagonize the effects of reserpine (758).

RIVAROXABAN (Xarelto) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of rivaroxaban.  Details A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20% (104038).

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.  Details Concomitant use of serotonergic drugs with St. John's wort can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstriction disorders (166,542,3569,8056,110318).

TACROLIMUS (Prograf) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of tacrolimus.  Details Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes (7095,10329).

THEOPHYLLINE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D St. John's wort might decrease the levels of theophylline, although this effect might not be clinically relevant.  Details St. John's wort does not seem to significantly affect theophylline pharmacokinetics (11802). There is a single case report of a possible interaction with theophylline. A patient who smoked and was taking 11 other drugs experienced an increase in theophylline levels after discontinuation of St. John's wort. This increase has been attributed to a rebounding of theophylline serum levels after St. John's wort was no longer present to induce metabolism via cytochrome P450 1A2 (CYP1A2) (3556,7808,9204). However, studies in healthy volunteers show that St. John's wort is unlikely to affect theophylline to any clinically significant degree (11802).

TRAMADOL (Ultram) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort might decrease the levels and clinical effects of tramadol.  Details St. John's wort can increase tramadol metabolism via induction of cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity (96552). Theoretically, concurrent use of St. John's wort with tramadol might also cause additive serotonergic effects (763,6427,8056,8936).

VORICONAZOLE (Vfend) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort might decrease the levels and clinical effects of voriconazole.  Details Clinical research shows that taking St. John's wort with voriconazole reduces voriconazole exposure and increases voriconazole metabolism by approximately 107%. Voriconazole is primarily metabolized by cytochrome P450 (CYP) 2C19, with CYP3A4 and CYP2C9 also involved (89660). St. John's wort induces CYP2C19, CYP3A4, and CYP2C9 (9204,10830,10847,10848,11889,11890,17405,22423,22424,22425)(22427,48603).

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of warfarin.  Details Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers (11890,15176). This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4 (11890). St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin (1292). In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption (10448).

ZOLPIDEM (Ambien) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B St. John's wort might decrease the levels and clinical effects of zolpidem.  Details In clinical research, concomitant use of zolpidem with St. John's wort decreased zolpidem plasma levels due to induction of its metabolism by cytochrome P450 3A4 (22441,96552). Whether this interaction is clinically significant is not known.

(Read more about ST. JOHN'S WORT)

General ...Orally, fresh cereus juice may cause burning of the mouth, queasiness, nausea, vomiting, and diarrhea (4,18).
Topically, it may cause itching and skin pustules (18).

(Read more about CEREUS)

General ...Orally, kava seems to be well tolerated.
Most Common Adverse Effects:
Orally: Drowsiness, dry mouth, dizziness, gastrointestinal upset, headache, memory problems, tremor.
Serious Adverse Effects (Rare):
Orally: There have been over 100 reported cases of hepatotoxicity and a few reported cases of rhabdomyolysis.

Cardiovascular ...Long-term use of very large amounts of kava, especially in high doses (400 mg kava pyrones daily), has been associated with overall poor health including symptoms of low body weight, reduced protein levels, puffy face, hematuria, increased red blood cell volume, decreased platelets and lymphocytes, and possibly pulmonary hypertension (4032,6402). Tachycardia and electrocardiogram (ECG) abnormalities (tall P waves) have been reported in heavy kava users (6402).

Dermatologic ...Orally, kava can cause allergic skin reactions, including sebotropic eruptions, delayed-type hypersensitivity, or urticarial eruption (4032,11370,28489,57277,57325,57343). Chronic use of high doses of kava has also been associated with kava dermopathy, which consists of reddened eyes; dry, scaly, flaky skin; and temporary yellow discoloration of the skin, hair, and nails (6240,6401,8414,8417,11370,28485,57342). This pellagra-like syndrome is unresponsive to niacinamide treatment (6240,7728,11370). The cause is unknown, but may relate to interference with cholesterol metabolism (6240). Kava's adverse effects on liver function might also contribute to kava dermopathy (6401,8417). Kava dermopathy usually occurs within three months to one year of regular kava use, and resolves when the kava dose is decreased or discontinued (6401,8414). Kava dose should be decreased or discontinued if kava dermopathy occurs (6401).

Gastrointestinal ...Orally, kava may cause gastrointestinal upset, nausea, or dry mouth (2093,2094,4032,11370,18316,57228,57343).

Hematologic ...Orally, chronic use of very high doses of kava has been associated with increased red blood cell volume, reduced platelet volume, reduced lymphocyte counts, and reduced serum albumin (6402,57258). Hematuria has also been reported anecdotally (6402).

Hepatic ...Since the early 2000's, hepatotoxicity has been a particular concern with kava. Worldwide, there have been at least 100 reported cases of hepatotoxicity following use of kava products (7024,7068,7086,7096,11795,17086)(57252,57254,57297). However, some experts question the clinical validity of several of these cases (11369,11371). Some cases were reported multiple times and in some cases it was unlikely that kava was the causative agent (7068,57253).
In susceptible patients, symptoms can show up after as little as 3-4 weeks of kava use. Symptoms include yellowed skin (jaundice), fatigue, and dark urine (7024,7068). Liver function tests can be elevated after 3-8 weeks of use, possibly followed by hepatomegaly and onset of encephalopathy (7024). Kava has also been reported to exacerbate hepatitis in patients with a history of recurrent hepatitis (390). However, in many cases, symptoms seem to resolve spontaneously, and liver function tests usually normalize within eight weeks (390,7068).
Liver toxicity is more frequently associated with prolonged use of very high doses (6401,57346). But there is some concern that even short-term use of kava in typical doses might cause acute hepatitis in some patients, including severe hepatocellular necrosis. The use of kava for as little as 1-3 months has resulted in need for liver transplant and death, although these events are rare (7024,7068,7086,7096,17086).
There is some speculation that the type of extraction method could be responsible for these rare cases of hepatotoxicity (17086). The "Pacific kava paradox" holds that while the alcohol and acetone extracts of kava used for commercial products cause liver toxicity, the traditional kava rhizome preparation mixed with water might not be toxic (11794,17086). However, a more recent analysis reports cases of hepatotoxicity from the aqueous kava extract and suggests that kava's hepatotoxic effects may be due to contaminants such as mold (29676). Other suggested causes of hepatotoxicity include quality of the kava plant, concomitant medications, large doses and prolonged use, and toxic constituents and metabolites of kava (57300,88532).
Some commercial kava extracts contain parts of the stems and other aerial parts in addition to the rhizome, and it has been suggested that a constituent called pipermethysine, which is only found in these aerial parts, might be partly responsible for hepatotoxicity (17086). Other constituents of kava which might contribute to hepatotoxicity are kavalactones, which are metabolized by cytochrome P450 (CYP450) enzymes in the liver. Reactive metabolites are produced which conjugate with glutathione, and might deplete glutathione in a similar manner to acetaminophen (17086). Increased levels of gamma-glutamyl transferase, involved in the production of glutathione, have been reported in chronic kava users (17086). One of the enzymes involved in production of reactive metabolites from kavalactones is cytochrome P450 2E1 (CYP2E1), which is induced by chronic alcohol intake. Alcohol may also compete for other enzymes which clear kavalactone metabolites from the body. This might explain the observation that alcohol ingestion seems to increase the risk of hepatotoxicity with kava (7068,17086).
There is also speculation that "poor metabolizers" or those patients with deficiency in the cytochrome P450 2D6 (CYP2D6) isoenzyme, which occurs in up to 10% of people of European descent, may be at increased risk for hepatotoxic effects from kava (7068). This deficiency has not been found in Pacific Islanders. However, this theory has not been confirmed.
Due to the concerns regarding the potential hepatotoxicity of kava, kava supplements were withdrawn from European and Canadian markets in 2002 (7086). However, many of the market withdrawals of kava have been lifted after re-evaluation of kava suggested that the risk of hepatotoxicity was minimal (91593,91594,91615). Still, clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend exercising caution when using kava in patients with preexisting liver issues (110318). Until more is known, tell patients to use kava cautiously and recommend liver function tests for routine users or those with underlying liver disease.

Immunologic ...Sjögren syndrome has been associated with an herbal supplement containing kava, echinacea, and St. John's wort. Echinacea may have been the primary cause, because Sjögren syndrome is an autoimmune disorder. The role of kava in this syndrome is unclear (10319).

Musculoskeletal ...Kava has been linked with reports of rhabdomyolysis. A 34-year-old man who consumed kava tea several times a week developed rhabdomyolysis with a peak creatine kinase level of 32,500 units/liter (18212). However, there is speculation that this might have been due to product impurities rather than kava itself. Another case report describes rhabdomyolysis with myoglobinuria and a creatine kinase level of 100,500 units/liter in a 29-year-old man who had taken kava in combination with guarana and ginkgo biloba (18213).
Cases of ataxia and tremors have been reported in patients taking single doses of kava powder 205 grams (11373).

Neurologic/CNS ...Orally, kava may cause headache, dizziness, and drowsiness (4032,6402,11370,11372,11373,18316,112642). It might also cause extrapyramidal side effects such as involuntary oral and lingual reflexes, twisting movements of the head and trunk, tremors, and other parkinsonian-like symptoms possibly due to dopamine antagonism (534,4055,7727,8415,102086). In one clinical trial, patients taking a kava supplement providing 120 mg of kavalactones twice daily for 16 weeks had a 3.2-fold greater risk of experiencing tremors when compared with patients taking placebo (102086). Theoretically, kava may worsen symptoms in patients with Parkinson disease or precipitate Parkinson-like symptoms in certain patients (4055,7727). Unlike benzodiazepines, kava is not thought to be associated with impaired cognitive function (2097,2098,11373,57332,57333). However, one clinical trial shows that taking a kava supplement providing 120 mg of kavalactones twice daily for 16 weeks increases the risk for memory impairment by 55% when compared with placebo (102086).
Orally, kava may reduce alertness and impair motor coordination in a dose-dependent manner. Some preliminary reports have noted a decline in accuracy of visual attention and slower reaction times after kava ingestion, particularly at higher doses and in combination with alcohol (11373,95926). Population research has also found that ingesting large amounts of kava tea (typically 50 times higher than what is used medicinally in the US) within a 12-hour period before driving increases the odds of being involved in a serious motor vehicle crash resulting in death or serious injury by almost 5-fold when compared to not drinking kava tea (95927). Use of normal doses of kava may also affect the ability to drive or operate machinery, and driving under the influence (DUI) citations have been issued to individuals observed driving erratically after drinking large amounts of kava tea (535). However, in computer-based driving simulator tests, there are no reported adverse effects of kava on performance (95926). Additionally, other research shows that consuming over 4400 mg of kavalactones over a 6-hour kava session does not seem to impair alertness or attention when compared with non-kava drinkers (103867). Similar research using a specific psychometric tool (Brain Gauge) shows that consuming approximately 3680 mg of kavalactones in a 6-hour kava session seems to impair temporal order judgment, which is associated with the brain's ability to track the order of events, when compared with non-kava drinkers. However, it does not seem to impact cognitive domains related to focus, accuracy, timing perception, plasticity, or fatigue when compared with non-kava drinkers (110435).

Ocular/Otic ...Orally, high doses of kava may cause eye irritation (7728). There is one case report of impaired accommodation and convergence, increased pupil diameter, and oculomotor disturbance following a single dose of kava (9920).

Psychiatric ...Apathy has been associated with traditional use of kava at high doses (57313).

Pulmonary/Respiratory ...Orally, kava may cause shortness of breath, possibly due to pulmonary hypertension (6402).

Renal ...Orally, kava may cause acute urinary retention (57349).

(Read more about KAVA)

General ...Orally, lobelia can cause nausea, vomiting, diarrhea, coughing, dizziness, tremors, and throat irritation. These adverse effects have been reported with doses as low as 50 mg (4,16414). Lobelia leaf can cause toxicity when taken in doses of 600 mg or higher. Symptoms of lobelia toxicity include sweating, tachycardia, convulsions, hypothermia, hypotension, coma, and death (4,11).

Cardiovascular ...Orally, high doses of lobelia leaf can cause toxicity. Symptoms of lobelia toxicity include tachycardia, hypotension, and death (4,11).

Gastrointestinal ...Orally, lobelia can cause nausea, vomiting, diarrhea, and throat irritation (4,16414).

Neurologic/CNS ...Orally, lobelia can cause dizziness and tremors. High doses of lobelia leaf can cause toxicity. Symptoms of lobelia toxicity include convulsions, coma, and death (4,11).

Pulmonary/Respiratory ...Orally, lobelia can cause coughing and throat irritation (4,16414).

Other ...Orally, high doses of lobelia leaf can cause toxicity resulting in death. Toxicity has been reported to occur at doses as low as 600 mg, with doses of 4000 mg or more considered to be fatal (4,11).

(Read more about LOBELIA)

General ...Orally, fresh pulsatilla is a toxic gastrointestinal irritant (4,19). It can also cause kidney and urinary tract irritation (2).
Topically, contact with the fresh plant can cause skin irritation, mucous membrane irritation, itching, and pustule formation known as ranunculus dermatitis (2). Allergic reactions to pulsatilla volatile oil have been documented with patch tests (4).
Inhalation of pulsatilla volatile oil may cause nasal mucosal and conjunctival irritation (4).

Dermatologic ...Topically, contact with the fresh plant can cause skin irritation, mucous membrane irritation, itching, and pustule formation known as ranunculus dermatitis (2).

Gastrointestinal ...Orally, fresh pulsatilla is a toxic gastrointestinal irritant (4,19).

Genitourinary ...Orally, fresh pulsatilla can cause urinary tract irritation (2).

Immunologic ...Topically, allergic reactions to the protoanemonin-containing volatile oil of pulsatilla have been documented with patch tests (4).

Ocular/Otic ...Inhalation of the protoanemonin-containing volatile oil of pulsatilla may cause conjunctival irritation (4).

Pulmonary/Respiratory ...Inhalation of the protoanemonin-containing volatile oil of pulsatilla may cause nasal mucosal irritation (4).

Renal ...Orally, fresh pulsatilla can cause kidney irritation (2).

(Read more about PULSATILLA)

General ...Orally, St. John's wort is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dizziness, dry mouth, gastrointestinal discomfort (mild), fatigue, headache, insomnia, restlessness, and sedation.
Topically: Skin rash and photodermatitis.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of suicidal ideation and psychosis after taking St. John's wort.

Cardiovascular ...In clinical research, palpitations have been reported for patients taking St. John's wort orally, although the number of these events was higher for the patients taking sertraline (76070). In one case report, an adult female developed recurrent palpitations and supraventricular tachycardia (SVT) within 3 weeks of initiating St. John's wort 300 mg daily. SVT and related symptoms responded to Valsalva maneuvers and did not recur after discontinuing therapy (106051).
Edema has also been reported in clinical research for some patients treated with St. John's wort 900-1500 mg daily for 8 weeks (10843). Cardiovascular collapse following induction of anesthesia has been reported in an otherwise healthy patient who had been taking St. John's wort for 6 months (8931). A case of St. John's wort-induced hypertension has been reported for a 56-year-old patient who used St. John's wort extract 250 mg twice daily for 5 weeks. Blood pressure normalized after discontinuation of treatment (76073). A case of new-onset orthostatic hypotension and light-headedness has been reported for a 70 year-old homebound patient who was taking multiple prescription medications and herbal products, including St. John's wort (76128). When all herbal products were discontinued, these symptoms improved, and the patient experienced improvement in pain control.

Dermatologic ...Both topical and chronic oral use of St. John's wort can cause photodermatitis (206,620,758,4628,4631,6477,13156,17986,76072,76148)(95506,110318). The average threshold dose range for an increased risk of photosensitivity appears to be 1.8-4 grams St. John's wort extract or 5-10 mg hypericin, daily. Lower doses might not cause this effect (4542,7808). For example, a single dose of St. John's wort extract 1800 mg (5.4 mg hypericin) followed by 900 mg (2.7 mg hypericin) daily does not seem to produce skin hypericin concentrations thought to be high enough to cause phototoxicity (3900,4542,76266). Females appear to have a higher risk of dose-related photosensitivity. In a dose-ranging, small clinical trial, almost all of the female participants experienced mild to moderate photosensitivity with paresthesia in sun-exposed skin areas after administration of St. John's wort (Jarsin, Casella Med) 1800 mg daily for 3-6 days. Symptoms resolved about 12-16 days after discontinuation (95506). Male participants reported no adverse effects at this dose, and both genders reported no adverse effects at lower doses. Light or fair-skinned people should employ protective measures against direct sunlight when using St. John's wort either topically or orally (628).
Total body erythroderma without exposure to sunlight, accompanied by burning sensation of the skin, has also been reported (8930). Orally, St. John's wort may cause pruritus or skin rash, although these events seem to occur infrequently (76140,76148,76245). A case of persistent scalp and eyebrow hair loss has been reported for a 24-year-old schizophrenic female who was taking olanzapine plus St. John's wort 900 mg/day orally (7811). Also, a case of surgical site irritation has been reported for a patient who applied ointment containing St. John's wort (17225).

Endocrine ...A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 67-year-old male with depression has been reported. During a 3-month period, the patient was taking St. John's wort 300 mg daily then increased to 600-900 mg daily with no adverse effects despite a low serum sodium level of 122mEq/L, elevated levels of urine sodium, and urine osmolality suggestive of SIADH. St. John's wort appeared to be the only contributing factor. The patient's sodium level normalized 3 weeks after discontinuation of St. John's wort (95508).

Gastrointestinal ...Orally, St. John's wort may cause dyspepsia, anorexia, diarrhea, nausea, vomiting, and constipation, although these events seems to occur infrequently (4897,13021,17986,76070,76071,76113,76146,76150,76271).

Genitourinary ...Orally, St. John's wort can cause intermenstrual or abnormal menstrual bleeding (1292,76056). However, this effect has occurred in patients who were also taking an oral contraceptive. Changes in menstrual bleeding might be the result of a drug interaction (1292,76056). Also, St. John's wort has been associated with anorgasmia and frequent urination when used orally (10843,76070).
Sexual dysfunction can occur with St. John's wort, but less frequently than with SSRIs (10843). A case of erectile dysfunction and orgasmic delay has been reported for a 49-year-old male after taking St. John's wort orally for one week. Co-administration of sildenafil 25-50 mg prior to sexual activity reversed the sexual dysfunction. Previously, the patient had experienced orgasmic delay, erectile dysfunction, and inhibited sexual desire when taking a selective serotonin reuptake inhibitor (sertraline) (4836).

Hepatic ...A case of acute hepatitis with prolonged cholestasis and features of vanishing bile duct syndrome has been reported for a patient who used tibolone and St. John's wort orally for 10 weeks (76135). A case of jaundice with transaminitis and hyperbilirubinemia has been reported for a 79 year-old female who used St. John's wort and copaiba (95505). Laboratory values normalized 7 weeks after discontinuation of both products.

Musculoskeletal ...Orally, St. John's wort may cause muscle or joint stiffness, tremor, muscle spasms, or pain, although these events appear to occur rarely (76070).

Neurologic/CNS ...St. John's wort may cause headache, dizziness, fatigue, lethargy, or insomnia (5096,13021,76070,76071,76113,76132,76133,76150,89666). Isolated cases of paresthesia have been reported for patients taking St. John's wort (5073). A case of subacute toxic neuropathy has been reported for a 35-year-old female who took St. John's wort 500 mg daily orally for 4 weeks (621).

Ocular/Otic ...There is concern that taking St. John's wort might increase the risk of cataracts. The hypericin constituent of St. John's wort is photoactive and, in the presence of light, may damage lens proteins, leading to cataracts (1296,17088). In population research, people with cataracts were significantly more likely to have used St. John's wort compared to people without cataracts (17088). Ear and labyrinth disorders have been possibly attributed to use of St. John's wort in clinical research, although these events rarely occur (76120).

Psychiatric ...St. John's wort can induce hypomania in depressed patients and mania in depressed patients with occult bipolar disorder (325,3524,3555,3568,10845,76047,76064,76137,110318). Cases of first-episode psychosis have been reported for females who used St. John's wort orally. In both cases, symptoms resolved following discontinuation of St. John's wort and treatment with antipsychotics for several weeks (13015,89664). Also, psychosis and delirium have been reported for a 76-year-old female patient who used St. John's wort for 3 weeks. The patient may have been predisposed to this effect due to undiagnosed dementia (76270). Restlessness, insomnia, panic, and anxiety have been noted for some patients taking St. John's wort orally (5073,13156,76070,76132,76268,76269,89665).
In isolated cases, St. John's wort has been associated with a syndrome consisting of extreme anxiety, confusion, nausea, hypertension, and tachycardia. These symptoms may occur within 2-3 weeks after it is started, in patients with no other predisposing factors. This syndrome has been diagnosed as the serotonin syndrome (6201,7811,110318). In one case, the symptoms began after consuming tyramine-containing foods, including aged cheese and red wine (7812). In an isolated case, a 51-year-old female reported having had suicidal and homicidal thoughts for 9 months while taking vitamin C and a St. John's wort extract. Symptoms disappeared within 3 weeks of discontinuing treatment (76111). A case of decreased libido has been reported for a 42-year-old male with mood and anxiety disorders who had taken St. John's wort orally for 9 months (7312).
St. John's wort has been associated with withdrawal effects similar to those found with conventional antidepressants. Headache, nausea, anorexia, dry mouth, thirst, cold chills, weight loss, dizziness, insomnia, paresthesia, confusion, and fatigue have been reported. Withdrawal effects are most likely to occur within two days after discontinuation but can occur one week or more after stopping treatment in some people. Occurrence of withdrawal symptoms may not be related to dose or duration of use (3569,11801).

Pulmonary/Respiratory ...Orally, St. John's wort may cause sore throat, swollen glands, laryngitis, sinus ache, sweating, and hot flashes, although the frequency of these events appears to be similar to placebo (76150).

Renal ...Orally, St. John's wort has been associated with a case report of acute kidney failure in a 46-year-old female after one dose of homemade St. John's wort tea. Three sessions of hemodialysis were required before there was full recovery (106741). However, causality is unclear since the patient had also been taking diclofenac intermittently for a month prior to developing kidney failure.

Other ...Sjogren's syndrome has been reported in a patient taking herbal supplements including St. John's wort, echinacea, and kava. Echinacea may have been the primary cause, because Sjogren's syndrome is an autoimmune disorder. The role of St. John's wort in causing this syndrome is unclear (10319).

(Read more about ST. JOHN'S WORT)