Anxiety Soother [Discontinued] by Herb Pharm

There is insufficient reliable information available about the effectiveness of Albizia julibrissin.

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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.

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POSSIBLY EFFECTIVE

• Anxiety. Orally, a specific lavender oil product (Silexan) seems to improve anxiety in some patients. Lavender oil aromatherapy and aromatherapy massage also seem to improve chronic and situational anxiety in some patients. Details: Most meta-analyses and clinical trials in patients with mild to severe anxiety show that taking capsules containing a specific lavender oil ingredient (Silexan, Dr Willmar Schwabe GmbH & Co. KG) 80-160 mg orally daily for 6-10 weeks improves anxiety when compared with placebo. However, heterogeneity and small sample sizes limit the validity of these findings (58077,58080,58098,95640,103061,103069). A meta-analysis of a subgroup of these clinical studies shows that taking Silexan 80 mg orally once daily for 10 weeks also reduces anxiety in patients with subthreshold anxiety disorders, which meet some but not all criteria for generalized anxiety disorder (97257). Limited research compares Silexan to the conventional medications paroxetine and lorazepam. One clinical study shows that taking Silexan 80 mg daily for 6 weeks improves anxiety and quality of sleep similarly to low-dose lorazepam (Ativan) 0.5 mg in adults with generalized anxiety disorder (58077). Another clinical study in adults with generalized anxiety disorder shows that taking Silexan 80-160 mg daily for 10 weeks reduces symptom severity similar to paroxetine 20 mg daily (93004). A network meta-analysis suggests that the higher dose of Silexan (160 mg) might be more effective when compared with paroxetine 20 mg or lorazepam 0.5 mg (103069). Limited research has assessed other oral formulations of lavender. A small clinical study in postmenopausal adults with mild to moderate anxiety shows that taking a dried lavender flower powder 500 mg twice daily for 8 weeks reduces anxiety by about 6% when compared with placebo, as measured on the State-Trait Anxiety Inventory Scale (97256). The clinical significance of this improvement is not clear. Meta-analyses of clinical trials in patients with chronic or situational anxiety show that inhalation aromatherapy or aromatherapy massage using lavender oil moderately reduces anxiety when compared with control. Most often, the control group received no intervention although occasionally they received standard or routine care. In some studies, plain water or diluted lemon juice were used as controls. Most treatments with lavender aromatherapy were given as single sessions of 1-30 minutes. However, occasionally multiple sessions were used (101720,103061,109974). Most other individual clinical trials of aromatherapy with lavender, alone or in combination with bergamot, are in agreement with these findings (58103,95637,97258,99713,101722,101724,108752,109854,109981), although some research does not support the use of lavender aromatherapy for anxiety (29504,58053,97258,101724,109853). The poor quality of most of the available research makes it difficult to determine which patients, if any, are most likely to benefit.
• Depression. Oral lavender, in the form of tea, tincture, powder, or a specific oil (Silexan), seems to reduce depressive symptoms in some patients. Early research also shows that lavender oil aromatherapy seems to improve symptoms of depression. Details: When used orally, lavender may be beneficial in some patients with depression. A meta-analysis of five clinical trials shows that oral lavender is moderately more beneficial than a control group for reducing symptoms of depression (109860). Most studies included in the analysis were low- to moderate-quality with variation in patient demographics. Studies in the analysis investigated the effects of oral lavender oil or powder in menopausal or postpartum patients, or in patients with major depression, and compared lavender with routine care, placebo, medication, or no intervention. Doses have included powdered lavender leaves 1-2 grams daily for 8 weeks, lavender tea made from 2 grams powder per teabag once or twice daily for 2 weeks, and a specific oral capsule containing lavender oil (Silexan, Dr. Willmar Schwabe GmbH & Co. KG) 80 mg daily for 70 days (103060,104433,109860). Other preliminary clinical research in patients with depressed mood shows that taking Silexan 80 mg daily for 6 weeks can improve depression scores by about 33% when compared to baseline (58098). Also, a small clinical study in patients with mild to moderate depression shows that drinking a tincture of lavender appears to be slightly less effective than imipramine; however, lavender might have some additive antidepressant effects when used in combination with imipramine (9792). The validity of these findings is limited by the lack of a placebo group and small study size. Lavender has also been taken in combination with other products. A small clinical study in patients with depression and anxious distress shows that taking 5 mL of a syrup containing lavender flower extract and Chinese dodder extract twice daily for 6 weeks seems to reduce depression to a similar degree as citalopram 20 mg daily (104437). It is unclear if the benefit is due to lavender, Chinese dodder, or the combination. Lavender oil aromatherapy has also been evaluated. A meta-analysis of nine clinical trials shows that lavender oil aromatherapy is moderately more beneficial than control for reducing symptoms of depression. Most studies included in the analysis were low- to moderate-quality with variation in patient demographics. Studies in the analysis investigated the effects of lavender oil aromatherapy in a variety of patient populations, and no studies were specific to patients with depression. Lavender aromatherapy was compared with no intervention, routine care, other aromatherapy oils, or distilled water (109860). However, in hospitalized patients undergoing microvascular breast reconstruction, lavender oil aromatherapy does not improve symptoms of perioperative depression when compared with coconut oil (109853). Lavender oil has also been studied in combination with other oils as aromatherapy. A small clinical study in community-dwelling older adults shows that inhalation or massage with lavender, sweet orange, and bergamot oils twice weekly for 8 weeks improves depressive symptoms in 55% to 65% of patients when compared with a control (98474). Another small clinical study in postmenopausal adults shows that a combination of aromatherapy with lavender and bergamot oils three times daily for 8 weeks along with routine care modestly improves symptoms of depression when compared with routine care alone (109981). It is unclear if any benefit is due to lavender, other ingredients, or the combination.
• Dysmenorrhea. Limited clinical research suggests that lavender oil aromatherapy might reduce dysmenorrhea symptoms. Details: A clinical study in young adults with dysmenorrhea shows that applying 3 drops of lavender oil to a piece of cotton and inhaling for 30 minutes daily for the first 3 days of menstruation modestly reduces pain when compared to inhaling the scent of diluted milk (95635). Another small clinical study in patients with dysmenorrhea shows that applying 3 drops of lavender oil to the hands and inhaling for 5 minutes every 6 hours for the first 3 days of menstruation seems to reduce abdominal pain and backache when compared with inhaling the scent of sesame oil (90510). Lavender oil has also been added to abdominal massage. A clinical crossover study in young females with dysmenorrhea shows that administering a gentle abdominal massage with lavender essential oil for 15 minutes moderately reduces pain immediately after treatment when compared with a massage with petrolatum (58106). It is unclear if the benefit persists after the end of the treatment. Additionally, because all available research has been conducted in the Middle East, it is unclear if these results can be extrapolated to other geographic locations.

POSSIBLY INEFFECTIVE

• Cancer-related pain. Using lavender oil for massage or as an aromatherapy diffusion does not seem to provide any additional pain relief in patients with advanced or terminal cancer. Details: Clinical research in patients with advanced or terminal cancer shows that diffusing lavender oil as aromatherapy or using lavender oil for massage does not improve pain scores when compared with control treatments without lavender oil (29504,58053).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alopecia areata. Topical lavender oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with alopecia areata shows that applying lavender oil in combination with essential oils from thyme, rosemary, and cedarwood daily for 7 months seems to improve hair growth in 44% of participants when compared with 15% of those using only carrier oils (5177). It is unclear if this effect is due to lavender oil, other oils, or the combination.
• Atopic dermatitis (eczema). Although there is interest in using topical lavender oil for eczema, there is insufficient reliable information about the clinical effects of lavender oil for this condition.
• Burns. It is unclear whether lavender oil aromatherapy is beneficial as adjunct treatment for reducing pain associated with dressing changes in children with burns. Details: Preliminary clinical research in young children with second-degree burns shows that lavender oil aromatherapy, provided as 0.5 mL dripped onto a gauze pad and placed 20 cm away from the child's nose for 15 minutes before a dressing change, modestly reduces pain severity at 1 and 30 minutes after the dressing change when compared with placebo aromatherapy with jojoba oil. Use of lavender oil aromatherapy also attenuated increases in heart and respiratory rates after the dressing change (109857).
• Canker sores. Topical lavender oil might improve canker sore healing and reduce swelling and pain. Details: A clinical study shows that applying 2 drops of lavender oil to canker sores three times daily might reduce redness, swelling, and pain when compared with placebo (58099).
• Colic. It is unclear whether lavender oil aromatherapy massage is beneficial for reducing colic symptoms in infants. Details: A small clinical trial shows that using lavender oil diluted with almond oil to massage the belly of infants for 5-15 minutes beginning at the onset of colic reduces average weekly crying times by about 7 hours when compared with infants not receiving aromatherapy massages (58096). It is unclear if this effect is due to lavender oil, massage, or the combination.
• Coronary artery bypass graft (CABG) surgery. Small clinical studies suggest that lavender aromatherapy might modestly improve sleep and reduce pain in patients who have undergone CABG surgery. Details: One small clinical study shows that placing three drops of lavender oil (Barich Essence Company) on the pillow every night for 5 nights modestly improves sleep quality, but not sleep latency, duration, or efficiency, when compared with placebo (109861). Another small clinical study shows that placing 2 drops of lavender oil on a cotton ball for overnight aromatherapy starting on the second evening after surgery modestly improves sleep quality on the second and third nights of use, but not the first night, when compared with distilled water (109856). Also, a small clinical study shows that applying 5 drops of lavender oil 20% to a gauze which is worn around the neck for 30 minutes after CABG surgery modestly reduces postoperative pain on the day of surgery and the day after surgery when compared with pre-aromatherapy pain levels. These changes were greater than those seen in patients inhaling distilled water (109850). However, one small clinical study shows that inhaling 2 drops of lavender oil 2% for 20 minutes on postoperative days 2 and 3 does not reduce mental stress when compared with placebo (93009).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral lavender is beneficial for olfactory dysfunction in patients with COVID-19. Details: A small preliminary clinical trial in patients with olfactory dysfunction related to COVID-19 shows that taking lavender syrup 9 mL twice daily for 3 weeks in combination with routine treatments modestly reduces symptoms when compared with routine treatments alone. However, there was no change in symptom scores or the percentage of patients with complete improvement in olfactory or taste dysfunction. The lavender syrup was made by preparing a water extract of the dried aerial parts and mixing with honey and water (109864).
• Dementia. Small clinical studies suggest that diffused aromatherapy with lavender oil may modestly improve agitation symptoms in patients with dementia; however, lavender oil applied to the patient or the patient's clothes might not be beneficial. Details: Some small and heterogeneous clinical studies in patients with dementia show that applying lavender oil aromatherapy via a diffuser for either 20 minutes twice daily, 2 hours daily, or once nightly for up to 3 weeks seems to improve agitation when compared with baseline, water, or a sunflower oil placebo (16393,58052,95632). However, using aromatherapy that is applied to the person's clothes or arms does not seem to help. Small clinical studies in patients with moderate or advanced dementia show that applying lavender oil to a pad attached to a patient's shirt does not reduce agitation when compared with placebo (12213,99710). Another clinical study in nursing home residents with dementia and frequent agitated behavior shows that applying 1 mL of 30% lavender oil to each forearm does not reduce agitation or improve mood when compared with applying placebo oil (93014).
• Diabetic neuropathy. It is unclear if lavender aromatherapy massage is beneficial for diabetic neuropathy. Details: Preliminary clinical research in patients with neuropathic pain related to diabetes shows that a gentle foot massage with lavender essential oil 3% in sunflower oil for 10 minutes nightly for 1 month reduces neuropathic pain and improves quality of life when compared with a placebo sunflower oil massage or routine care alone (109858).
• Fall prevention. It is unclear if lavender aromatherapy prevents falls in elderly patients. Details: A clinical study in nursing home residents aged 65 years or older shows that attaching a patch with lavender oil (Aromaseal Lavender, Hakujuji Co.) onto the neckline of clothing once daily for one year seems to have a non-significant trend toward reduced fall incidence when compared with placebo (58101).
• Fatigue. Small clinical studies suggest that lavender aromatherapy may modestly reduce fatigue in patients with underlying medical conditions, such as kidney failure or heart disease. The effects of lavender for fatigue in otherwise healthy adults is unclear. Details: Most small clinical studies in adults with kidney failure show that receiving aromatherapy with lavender essential oil during hemodialysis sessions for 4 weeks reduces fatigue when compared with baseline, a control group, or a placebo group (98524,109867). However, one small clinical study in these patients shows that applying lavender oil for inhalation for 10 minutes during dialysis sessions for 4 weeks does not reduce fatigue when compared with control (95642). Lavender aromatherapy has also been tried in patients hospitalized with various forms of cardiac disease. A small clinical trial shows that placing 3 drops of lavender oil on a cotton ball and inhaling for 20 minutes nightly for 7 days improves fatigue scores by 21 points, compared with a 2-point improvement in those receiving placebo (107959). The validity of these findings is limited due to the short duration of treatment.
• Hypertension. Although there is interest in using lavender aromatherapy for hypertension, there is insufficient reliable information about the clinical effects of lavender for this condition.
• Insect repellent. Although there is interest in using topical lavender to repel insects, there is insufficient reliable information about the clinical effects of lavender for this condition.
• Insomnia. Inhalation aromatherapy or aromatherapy massage with lavender oil may improve some subjective measures of sleep, but results are conflicting and improvements appear minimal at best. Additionally, most small clinical studies suggest it does not improve sleep in hospitalized patients. Details: Lavender oil aromatherapy seems to improve sleep quality in some patients, although it is unclear which patient populations may be most likely to be benefit. A clinical study in healthy college students with self-reported sleep problems shows that wearing a patch containing lavender oil 55 mcL on the chest, in addition to practicing sleep hygiene, improves self-reported sleep quality, but not sleep quantity, when compared with wearing a placebo patch (93012). Another small clinical study in elderly patients that have trouble sleeping in nursing homes shows that placing 2 drops of lavender oil to a cotton pad on a nightstand at bedtime for 4 weeks moderately improves sleep quality and reduces fatigue when compared with control (103062). A meta-analysis of three clinical trials shows that lavender modestly improves postpartum sleep quality when compared with control, including placebo or no intervention. However, each trial used a different form of lavender, including a topical cream, a tea, and aromatherapy. Also, the individual trials included in the analysis show that only the cream and aromatherapy resulted in statistically significant improvements in sleep quality (109866). Conversely, a small clinical study in postmenopausal adults with insomnia who received sleep hygiene guidance shows that inhaling lavender oil 6% before bed nightly for 1 month does not improve sleep quality when compared with sunflower oil. The oil was inhaled from the bottle for two, two-minute sessions and then poured on a cotton ball and placed near the head while sleeping (109852). Lavender aromatherapy has also been evaluated for insomnia in patients with comorbid disease states. A clinical study in patients with insomnia and type 2 diabetes shows that lavender oil aromatherapy for 5 minutes at bedtime nightly for 4 weeks improves sleep when compared with almond oil (103065). Preliminary clinical research in adults with kidney failure shows that foot massage with lavender oil 1.5% for 3 weeks during hemodialysis modestly improves sleep quality when compared with routine care, but is no more effective than sweet orange oil (109859). Another preliminary clinical study in cancer patients shows that receiving aromatherapy as two drops of pure lavender oil applied to a cotton ball and attached to the collar for 20 minutes at bedtime for one week improves sleep when compared with baseline, but seems to be no better than using peppermint oil or a lavender oil 1% control (103063). The validity of this finding is limited because the lavender oil 1% control resulted in notable benefit and might have been an inadequate control treatment. Aromatherapy with lavender oil does not seem to improve sleep in most hospitalized patients, including patients in intermediate care units, hospitalized cardiac patients, and in patients undergoing microvascular breast reconstruction. Aromatherapy treatments have included lavender aromatherapy throughout hospitalization, placing 3 mL of lavender oil 3 feet away from the bed during sleep, and hand and lower leg massage with lavender essential oil 1.5% in sweet almond oil at bedtime (93013,101727,109853). However, studies have generally been small and did not use proper controls. Also, some small clinical studies suggest that lavender aromatherapy might have modest beneficial effects in patients undergoing coronary artery bypass graft (CABG) surgery (109856,109861).
• Kidney failure. Small clinical studies suggest that lavender aromatherapy may modestly reduce fatigue and improve sleep quality in adults receiving hemodialysis. Lavender oil massage may also modestly improve symptoms of restless leg syndrome (RLS) in these patients. Details: Multiple small studies have evaluated lavender aromatherapy, provided during hemodialysis sessions, for reducing fatigue. A small clinical study shows that applying 5% lavender essential oil (Barij Essence Pharmaceutical Company) to a cotton ball on the patient's collar for inhalation for 15-20 minutes twice daily during each session for 1 month reduces fatigue by an additional 44% and 40% when compared with baseline and control, respectively (98524). Another preliminary clinical trial shows that applying lavender oil 7% in sweet almond oil to a gauze pad placed 20 cm from the patient's nose for 2 minutes improves fatigue when compared with placebo aromatherapy. By the third week of four total weeks of treatment, most patients given lavender oil aromatherapy had only mild fatigue, compared with moderate or severe fatigue in the control group (109867). Also, a small clinical trial shows that aromatherapy or aromatherapy foot massage with lavender and sweet orange oil for 10-20 minutes during each session for 2 months reduces fatigue when compared with no treatment. Aromatherapy massage seems to be more effective than aromatherapy alone (103068). However, one small clinical study shows that applying the oil for inhalation for 10 minutes during each session for 1 month does not reduce fatigue when compared with control (95642). The difference in these findings might be due to study size, lavender oil concentration, or the frequency and duration of aromatherapy sessions. Lavender aromatherapy has also been evaluated for reducing insomnia in adults on hemodialysis. A small clinical study shows that foot massage with lavender oil 1.5% for 3 weeks during hemodialysis sessions modestly improves sleep quality when compared with routine care. However, it does not seem to be more effective than using sweet orange oil (109859). Some small clinical studies in patients undergoing hemodialysis show that massaging the feet or lower legs with lavender oil reduces the severity of RLS by up to 45% when compared with routine care, massage only, or baby oil as placebo (95638,103064,109865). However, massage with lavender oil does not seem to be more beneficial than glycerin oil 2% or sweet orange oil 1.5% for reducing RLS severity (103064,109859). Doses have included 10-15 mL of 1.5% or 5% lavender oil for 10- to 45-minutes during hemodialysis sessions for 3-4 weeks (95638,103064,109859,109865).
• Labor pain. Lavender aromatherapy may help to reduce pain during childbirth. Details: A meta-analysis of clinical trials in pregnant patients in Iran shows that lavender oil aromatherapy applied by various means, such as mask or massage, reduces labor pain when compared with control (104440). All available research has been conducted in Iran, so it is unclear if the benefit can be extrapolated to other geographic locations.
• Lice. Topical lavender oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: Clinical studies in patients with head lice shows that applying lavender oil in combination with tea tree oil reduces the number of hatched and unhatched live lice when compared with control (19188,19189). When applied with tea tree oil three times weekly, lavender oils seems to improve lice eradication when compared with two weekly treatments of pyrethrin and piperonyl butoxide (19189). It is not known if these effects are due to tea tree oil, lavender, or the combination.
• Menopausal symptoms. It is unclear if lavender aromatherapy reduces menopausal symptoms such as hot flushes. Details: A meta-analysis and individual clinical studies in postmenopausal adults show that lavender aromatherapy for 4-12 weeks, alone or in combination with other essential oils, reduces menopausal symptoms such as hot flushes when compared with placebo (95634,99711,103067). However, heterogeneity and small sample sizes limit the validity of these findings. A small clinical study in postmenopausal adults shows that aromatherapy with lavender 2% oil for 20 minutes at bedtime every day for 1 month improves quality of life scores when compared to baseline (99711). Another small clinical study in menopausal adults shows that receiving aromatherapy with lavender oil and lemon oil for 5 minutes daily for 30 days seems to improve sleep and quality of life when compared with placebo (104439). However, a small clinical study in postmenopausal adults shows that a combination of lavender and bergamot oils administered via inhalation three times daily for 8 weeks with routine care does not improve sexual function when compared with routine care alone (109981).
• Migraine headache. It is unclear if lavender aromatherapy improves migraine symptoms. Details: A small clinical study in patients with migraine headaches shows that rubbing 2-3 drops of lavender oil on the upper lip for inhalation might reduce headache pain and associated symptoms such as nausea and photophobia. Of 129 headaches treated with lavender oil, 92 responded completely or partially, compared with 32 of 68 headaches in the placebo group (18209).
• Multiple sclerosis (MS). It is unclear if lavender aromatherapy can improve memory in patients with MS. Details: A small preliminary clinical trial in patients with MS shows that dripping 2 drops of lavender oil (Barij Essence Pharmaceutical Company) on a cotton ball for inhalation for 10 minutes twice daily for 2 weeks improves working memory by a small amount when compared with inhaling distilled water (109855).
• Multiple sclerosis-related fatigue. It is unclear if oral lavender is beneficial for reducing fatigue in adults with multiple sclerosis (MS). Details: A small clinical trial in patients with MS shows that taking lavender 600 mg three times daily for 60 days improves fatigue by a large amount when compared with placebo (109851).
• Neuropathic pain. Although there is interest in using topical lavender oil for neuropathic pain, there is insufficient reliable information about the clinical effects of lavender for this condition.
• Osteoarthritis. It is unclear if lavender aromatherapy with massage reduces osteoarthritis pain. Details: A small clinical study in patients with osteoarthritis shows that applying 5 mL of 3% lavender oil (Barij Essence Pharmaceutical Company) to the knee through self-administered massage three times weekly for 3 weeks can reduce pain by 23% when compared to massage with placebo oil and by 36% when compared with no treatment. However, any benefits of treatment begin to wear off after treatment completion (95645).
• Otitis media. Topical lavender oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: A clinical study in children ages 5-18 years with otitis media and otalgia shows that administering ear drops containing lavender and other herbal extracts, alone or in combination with a topical anesthetic, improves ear pain when compared with baseline. However, it is possible that the pain is self-limited and any pain reduction is due to natural resolution (39500).
• Pain (acute). Small clinical studies suggest that lavender aromatherapy may modestly reduce acute pain from needle insertion or other procedures in infants and adults. Details: Two small clinical studies in patients having a needle inserted for hemodialysis shows that inhaling 10% lavender essence for 5 minutes or topically applying 0.3 mL of 100% lavender oil for 5 minutes prior to needle insertion modestly reduces pain when compared with using placebo oil or water (93008,93010). Lavender aromatherapy has also been tried for gynecological exam pain. A clinical study shows that inhaling 10% lavender oil from a heat lamp for 10-15 minutes prior to gynecological exams can reduce pain experienced during the exam up to three-fold when compared to those receiving no treatment (95639). Lavender oil aromatherapy may also reduce vaccination, needle stick, and heel-lancing pain in infants. One clinical study shows that inhaling the scent of lavender oil (Barij Essence Pharmaceutical Company) 0.5% drops for one minute before vaccination modestly reduces pain and decreases crying time by about 20 seconds when compared with sweet almond oil (109869). A small clinical study in term infants shows that being placed in an incubator with lavender essential oil scent overnight before receiving a blood draw modestly reduces overall pain scores when compared with no intervention, but seems to be no different than giving 2 mL of 30% glucose solution (103066). Another small clinical study in premature infants shows that inhaling the scent of 6 lavender oil drops on a cotton ball for 3 minutes before and 30 seconds after a heel-lancing procedure seems to reduce pain scores when compared with exposure to an unscented cotton ball (104442). Lavender oil aromatherapy may also reduce pain due to frenotomy in infants. Preliminary clinical research shows that applying a gauze pad containing one drop of lavender oil under the nose, starting 2 minutes before the frenotomy and continuing throughout the procedure, modestly reduces pain when compared with routine care, which includes swaddling, oral sucrose, and pre-frenotomy sucking. Post-frenotomy crying was also reduced by about 50%, or 10 seconds (109868). Lavender oil seems to be similarly effective to vanilla oil (109810).
• Postdural puncture headache. It is unclear if lavender aromatherapy improves postdural puncture headache severity. Details: A small clinical study in patients with postdural puncture headache shows that receiving lavender oil aromatherapy for 15 minutes modestly improves pain immediately after treatment when compared with placebo. However, the pain relief is not maintained at 30 minutes after treatment (104441).
• Postoperative nausea and vomiting (PONV). It is unclear if lavender aromatherapy reduces PONV. Details: A small clinical study in postoperative patients shows that inhaling the scent of 2 drops of lavender oil from a cotton pad for 5 minutes improves nausea scores in 83% of people, compared with 44% of those inhaling a placebo. There was no difference in vomiting scores between groups (99712). Another small clinical study in patients after percutaneous nephrolithotomy shows that inhaling the scent of 3 drops of lavender essential oil from a gauze for 5 minutes immediately after the operation, and again 3 and 6 hours later, does not improve nausea or vomiting when compared with a control group that was not receiving aromatherapy (103872).
• Postoperative pain. The evidence for the use of lavender aromatherapy for pain after various types of surgical procedures is preliminary and conflicting. Details: Some preliminary clinical research in patients post-Cesarean section shows that, when used in conjunction with standard analgesic therapy, applying 2 drops of lavender oil 2% to a face mask or applying 3 drops of lavender to a cotton ball for inhalation seems to reduce postoperative pain when compared with control (58093,101724). Additionally, preliminary clinical research in patients undergoing coronary artery bypass graft (CABG) surgery shows that applying lavender oil to a gauze which is worn around the neck may modestly reduce postoperative pain on the day of surgery and the day after surgery when compared with distilled water (109850). Also, a small clinical study in children aged 6-12 years post-tonsillectomy shows that rubbing lavender oil onto the palms and inhaling for 3 minutes every 6 hours as needed reduces the use of acetaminophen when compared with control (90513). However, aromatherapy with lavender throughout hospitalization does not seem to improve postoperative pain in patients undergoing microvascular breast reconstruction when compared with coconut oil (109853).
• Postpartum complications. It is unclear if topical or inhaled lavender reduces postpartum complications such as pain and swelling. Details: Some clinical research in patients receiving an episiotomy during childbirth shows that adding lavender oil to water or sitz baths for up to 10 days might reduce episiotomy redness and discomfort when compared with using no lavender and standard treatment, such as povidone-iodine. However, findings are mixed as to whether adding lavender oil to baths helps to reduce edema and analgesic use (58085,58092,58116,58121). Lavender aromatherapy has also been studied to improve wellbeing in postpartum patients. A small clinical study in postpartum patients immediately following a natural birth shows that inhaling lavender oil from a cotton ball for 10-15 minutes in the morning, 6 hours later, and at bedtime, improves perceived pain, fatigue, distress, and mood within 1 hour of treatment and also the next morning when compared with placebo (95631).
• Postpartum depression. Small clinical studies suggest that aromatherapy with lavender oil may modestly improve or prevent depressive symptoms in postpartum patients. Details: A clinical study in healthy postpartum patients shows that placing 3 drops of lavender essential oil on the palms three times daily for 4 weeks after delivery moderately reduces depressive symptoms and anxiety when compared with usual care only (95637). There is limited research on the benefits of lavender aromatherapy in patients diagnosed with postpartum depression. A small clinical trial in these patients shows that a combination of lavender and rose essential oils, administered via inhalation or aromatherapy massage using hand "M" technique for 15-minute sessions, twice weekly for 4 weeks, reduces depression scores when compared with no intervention (58103).
• Pre-procedural anxiety. It is unclear if lavender aromatherapy can reduce preoperative or preprocedural anxiety; results from clinical research are generally of low-quality and benefits are modest at best. Details: A meta-analysis of four small clinical studies in patients undergoing cardiac surgery shows that lavender aromatherapy modestly reduces preoperative anxiety when compared with control (103058). However, the included studies were conducted in the Middle East, and it is unknown if these results are generalizable to other geographic areas. There is conflicting clinical evidence regarding the effect of lavender aromatherapy on anxiety prior to a dental procedure (58078,101725,103059). Small clinical studies also show mixed results as to whether lavender oil aromatherapy applied to a gauze bandage or oxygen mask improves anxiety in patients waiting for breast surgery when compared with usual care. (95641,101729). Lavender aromatherapy might reduce anxiety prior to less risky and extensive procedures such as needle injections. Small clinical studies in adults receiving botulinum toxin type A injections or children receiving dental injections show that lavender oil aromatherapy reduces heart rate and cortisol levels when compared with placebo (58089,104438). Another clinical study in preoperative patients undergoing insertion of a peripheral venous cannula shows that inhalation of 1% lavender oil (Talya Herbal Products) from a gauze pad for 5 minutes modestly reduces pain and anxiety scores and improves patient satisfaction when compared with control (95636). However, a clinical study in patients undergoing a colonoscopy or esophagogastroduodenoscopy shows that inhaling lavender oil does not reduce anxiety, although it does improve patient satisfaction, when compared with placebo (58066). Reasons for conflicting findings are unclear but may relate to the severity of anxiety, the specific outcomes measured, and cultural differences occurring in different geographic locations.
• Psychological well-being. It is unclear if topical or inhaled lavender improves well-being. Details: A small clinical study in healthy females shows that adding 3 mL of a mixture containing 20% lavender oil and 80% grapeseed oil to daily baths modestly improves mood when compared with baths containing grapeseed oil alone (15534). However, lavender may not impact well-being in patients with cancer. Clinical research shows that that adding lavender oil for an aromatherapy massage in patients with advanced or terminal cancer does not improve well-being or quality of life when compared with no massage treatment or massage with inert oil (29504,58053).
• Restless legs syndrome (RLS). Most preliminary clinical research suggests that lavender oil aromatherapy massage is beneficial for RLS in patients undergoing hemodialysis. Its effect in other patient populations is unclear. Details: Some small clinical studies in patients undergoing hemodialysis show that massaging the feet or lower legs with lavender oil reduces the severity of RLS by up to 45% when compared with routine care, massage only, or baby oil as placebo (95638,103064,109865). However, massage with lavender oil does not seem to be more beneficial than glycerin oil 2% or sweet orange oil 1.5% for reducing RLS severity (103064,109859). Doses have included 10-15 mL of 1.5% or 5% lavender oil for 10 to 45 minutes during hemodialysis sessions for 3-4 weeks (95638,103064,109859,109865).
• Stress. Small studies suggest that inhaled lavender oil does not reduce stress in students under academic stress. Details: A meta-analysis of 21 moderate- to high-quality, small- to medium-sized studies shows that inhaling lavender oil modestly reduces stress when compared with control. Most studies included in the analysis have used lavender oil as aromatherapy; other studies have used a cream (109863). Also, inhaling lavender oil 3% in almond oil twice daily for 30 minutes during the exam period does not reduce academic stress or associated symptoms, including headache, blood pressure, or heart rate, in pharmacy students when compared with inhaling an odorless oil, although both were more effective than no intervention (101723).
• Toothache. Although there is interest in using topical lavender oil for toothache, there is insufficient reliable information about the clinical effects of lavender oil for this purpose. More evidence is needed to rate lavender for these uses.

(Read more about LAVENDER)

POSSIBLY EFFECTIVE

• Anxiety. Oral passion flower has a long history of use as a sedative and may improve symptoms of anxiety in some patients. Details: Preliminary clinical research shows that taking a specific dried alcoholic extract of passion flower (Sedanxio, Tilman SA) 400 mg orally twice daily for 2-8 weeks reduces the severity of non-specific anxiety when compared to baseline (88198). The validity of this finding is limited by the lack of a placebo group. Passionflower has also been evaluated as an adjunct to conventional medication. One clinical small study in patients with generalized anxiety disorder shows that taking a specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) 15 drops three times daily along with sertraline 50-100 mg daily for one month reduces anxiety when compared with taking sertraline alone (95036). Passion flower has also been compared to conventional treatments. One preliminary clinical study shows that taking passion flower extract 90-180 mg daily reduces symptoms of non-specific anxiety when compared to baseline, and seems to be comparable to taking mexazolam (15391). A small clinical study in patients with generalized anxiety disorder shows that taking a specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) 45 drops orally once daily for 28 days reduces anxiety similarly to oxazepam 30 mg daily. However, passion flower appears to have a slower onset of action than oxazepam (8007). This finding is limited because it did not utilize a therapeutic dosing regimen for oxazepam, which is given 3-4 times daily to account for its short half-life. Passion flower has also been studied in combination with other ingredients. A small clinical study in healthy adults shows that taking a combination of herbal extracts containing passion flower 40 mg, valerian root, black horehound, and hawthorn (Euphytose, Bayer HealthCare) 6 times daily with meals for 14 days reduces anxiety and sympathetic and autonomic nervous system activation in response to a psychosocial stressor when compared with placebo (111222). It is unclear if these effects are due to valerian, other ingredients, or the combination.
• Pre-procedural anxiety. Oral passion flower modestly reduces preoperative anxiety. Details: Two small clinical studies in adults awaiting dental surgery or inguinal hernia repair surgery shows that taking a specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) reduces preoperative anxiety when compared with placebo. Passion flower extract was given as 20 drops or 500 mg 90 minutes prior to surgery, with or without another dose on the evening before surgery (88195,88196). Another small clinical study shows that drinking 5 mL of syrup containing passion flower aqueous extract (Passiflora syrup, Sandoz) 700 mg orally 30 minutes before epidural catheter insertion for inguinal hernia repair surgery seems to attenuate anxiety; the placebo group experienced a significant increase in anxiety (88194). This finding is limited because there were no statistical comparisons conducted between groups. Passion flower has also been compared with conventional medications. Three clinical studies show that taking passion flower prior to dental surgery decreases preoperative anxiety similarly to oral midazolam 15 mg. One study used passion flower 260 mg, administered 30 minutes prior to the surgery (95038), the second used 500 mg, administered 60 minutes prior (104206), and the third used 600 mg, administered 45 minutes prior (110014). Of the two studies that evaluated patient preference, patients in one study preferred midazolam, possibly due to its ability to cause perioperative amnesia (95038), whereas there was no preference in the other study (110014). Another clinical study shows that taking passion flower 1000 mg one hour prior to elective minor or moderate surgery reduces preoperative anxiety similarly to melatonin 6 mg; however, passion flower seems to cause more cognitive impairment than melatonin (95037).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Adjustment disorders. Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients with adjustment disorder with anxious mood shows that taking two tablets of a specific combination product (Euphytose, Bayer Healthcare) three times daily seems to decrease anxiety symptoms when compared with placebo. One tablet contains the dry extracts of passion flower 40 mg, valerian 40 mg, hawthorn 10 mg, and black horehound 10 mg, as well as the caffeine-containing stimulant herbs kola nut 15 mg and guarana 15 mg (6250). It is unclear if this effect is due to passion flower, other ingredients, or the combination.
• Alcohol use disorder. Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults experiencing alcohol withdrawal symptoms shows that taking one capsule of a combination product (Relief) three times daily for 15 days reduces the frequency of excessive sweating, reduces serum liver enzyme levels, and improves appetite and quality of life when compared to baseline. One capsule contains passion flower extract 30 mg, black seed extract 100 mg, cocoa extract 90 mg, radish extract 165 mg, and saffron extract 15 mg (97280). The validity of these findings is limited by the lack of a comparator group.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral passion flower is beneficial in patients with ADHD. Details: A small clinical trial in children aged 6-13 years with ADHD shows that taking tablets of passion flower (Pasipay, Iran Darouk Pharmaceutical Company) 0.02 mg/kg orally twice daily for 8 weeks reduces parent and teacher ratings of ADHD symptoms no better than taking methylphenidate (0.5 mg/kg twice daily) (88197).
• Benzodiazepine withdrawal. It is unclear if oral passion flower is beneficial for benzodiazepine withdrawal. Details: A moderate-sized observational study in adults with depression or anxiety on antidepressants undergoing a benzodiazepine taper after chronic benzodiazepine use suggests that taking a specific dry extract of passion flower (Tractana, Baldacci) 200-600 mg daily for 3 months is associated with a faster benzodiazepine dose reduction and greater percentage of patients with at least 50% reduction or complete benzodiazepine discontinuation after 1 and 3 months from taper initiation when compared with control (111651). The validity of these effects is limited by a lack of placebo group and the retrospective observational study design.
• Congestive heart failure (CHF). Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild CHF shows that taking a combination of passion flower and hawthorn extracts 2 mL three times daily for 6 weeks increases six-minute walking distance when compared with placebo. However, it does not appear to improve exercise capacity on a bicycle ergometer test (19201). It is unclear if this effect is due to passion flower, hawthorn, or the combination. Additionally, hawthorn has been evaluated alone for the management of CHF, with some research suggesting that although it may improve symptoms, it may also be associated with worsened clinical outcomes.
• Fibromyalgia. Although there is interest in using oral passion flower for fibromyalgia, there is insufficient reliable information about the clinical effects of passion flower for this condition.
• Insomnia. Small clinical studies suggest that oral passion flower may modestly improve sleep quality in patients with insomnia and poor sleep quality. Details: Some preliminary clinical research in adults with insomnia shows that taking passion flower extract 60 mg every evening before bedtime for 2 weeks increases total sleep time by around 23 minutes, but doesn't seem to improve sleep efficiency, sleep latency, or awakening after sleep onset, when compared with placebo (102866). Another smaller clinical study in young adults with mild fluctuations in sleep quality shows that drinking tea prepared by steeping passion flower aerial parts 2 grams in 250 mL of boiling water for 10 minutes every evening, about an hour before bedtime for 7 nights, improves subjective ratings of sleep quality, but not other sleep parameters, when compared with placebo (parsley tea) (17374). Passion flower has also been studied in combination with other ingredients. One small clinical study in adults with primary insomnia shows that taking a specific combination product containing passion flower 80 mg, valerian 300 mg, and hops 30 mg (NSF-3, M/s Tablets India) orally at bedtime for 2 weeks yields similar effects on subjective measures of sleep as zolpidem 10 mg nightly (88193).
• Menopausal symptoms. Although there is interest in using oral passion flower for menopausal symptoms, there is insufficient reliable information about the clinical effects of passion flower for this purpose.
• Muscle cramps. Although there is interest in using oral passion flower for muscle cramps, there is insufficient reliable information about the clinical effects of passion flower for this purpose.
• Neuropathic pain. Although there is interest in using oral passion flower for neuropathic pain, there is insufficient reliable information about the clinical effects of passion flower for this condition.
• Opioid withdrawal. It is unclear if oral passion flower helps to prevent opioid withdrawal. Details: A small preliminary clinical study in adults who are completing an inpatient withdrawal program for opioid addiction shows that taking passion flower liquid extract 60 drops, in combination with clonidine 0.8 mg daily, is better than clonidine alone when used for reducing symptoms such as anxiety, irritability, insomnia, and agitation. However, the combination is no better than clonidine alone for reducing physical symptoms such as tremor and nausea (2303).
• Seizures. Although there is interest in using oral passion flower for seizures, there is insufficient reliable information about the clinical effects of passion flower for this condition.
• Stress. Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults shows that taking a specific combination product (Relaxane, Max Zeller Söhne AG) containing passion flower 90 mg, lemon balm 50 mg, valerian 90 mg, and butterbur 90 mg three times daily for 3 days modestly reduces subjective anxiety scores during social stress testing when compared with placebo or no treatment (97276). It is unclear if this effect is due to passion flower, other ingredients, or the combination. More evidence is needed to rate passion flower for these uses.

(Read more about PASSION FLOWER)

There is insufficient reliable information available about the safety of Albizia julibrissin.

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

(Read more about ALBIZIA JULIBRISSIN)

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 SAFE ...when used orally in amounts commonly found in foods. Lavender has Generally Recognized as Safe (GRAS) status for food use in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (9792). In clinical research, a specific product containing lavender oil (Silexan, Dr Willmar Schwabe GmbH & Co. KG) has been used safely at doses of 80-160 mg daily for up to 10 weeks (58077,58080,58098,97257). Powdered dried lavender flowers 500 mg twice daily has also been used with apparent safety for up to 8 weeks (97256). ...when used topically and appropriately. Lavender oil has been used safely for up to 7 months in adults (5177,109858,109865). ...when the essential oil is inhaled as a part of aromatherapy. Clinical studies have used lavender oil aromatherapy with apparent safety for up to 12 weeks (7107,12213,16393,16394,95634,103062,103063,103065,103068).

CHILDREN: POSSIBLY SAFE
when the essential oil is inhaled as a part of aromatherapy. Clinical studies have used lavender oil aromatherapy with apparent safety in single doses for up to 2 minutes (109868).

CHILDREN: POSSIBLY UNSAFE
when applied topically in males. Anecdotal reports suggest that applying topical products containing lavender oil to prepubertal males may result in gynecomastia in some cases (15254,95643). Products with a higher concentration of lavender oil and more frequent applications might be more likely to result in gynecomastia.

PREGNANCY AND LACTATION:
Insufficient reliable evidence available. Preliminary clinical research shows that lavender essential oil can be inhaled during labor, with no apparent adverse outcomes in the infants (95633). Although this study suggests safety, high quality assessment of safety has not been conducted.

(Read more about LAVENDER)

LIKELY SAFE ...when used orally as a flavoring in foods. The US Food and Drug Administration (FDA) lists passion flower as a permitted food flavoring additive, to be used in the minimum quantity necessary (91203).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Passion flower extract has been used with apparent safety at doses up to 800 mg daily for up to 8 weeks (88198,102866). A specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) has been safely used at a dose of 45 drops daily for up to one month (8007,95036). Also, a tea prepared by steeping 2 grams of the dried aerial parts of passion flower in 250 mL of boiling water for 10 minutes has been used nightly for 7 nights (17374). There is insufficient reliable information available about the safety of passion flower when used topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific passion flower product (Pasipay, Iran Darouk Pharmaceutical Company) has been used safely in children aged 6-13 years at a dose of 0.04 mg/ kg daily for 8 weeks (88197).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Some case reports suggest that passion flower use during the first and second trimesters of pregnancy may be associated with an increased risk for premature rupture of membranes and meconium aspiration syndrome; however, causality has not been confirmed (97279). The alkaloids harman and harmaline, which are sometimes found in passion flower, have been reported to have uterine stimulant activity (4,11020,95037). It is not known whether these constituents are present in sufficient quantities to have an effect.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PASSION FLOWER)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that certain constituents from Albizia julibrissin flowers can potentiate pentobarbital-induced sleeping time in mice (20022). Theoretically, Albizia julibrissin might enhance the therapeutic and adverse effects of CNS depressants.  Details Some CNS depressants include pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), clonazepam (Klonopin), lorazepam (Ativan), zolpidem (Ambien), and others.

(Read more about ALBIZIA JULIBRISSIN)

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)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, lavender might potentiate the therapeutic effects and adverse effects of CNS depressants.  Details Laboratory research suggests that lavender has sedative effects (7). However, clinical studies in patients taking oral lavender oil (Silexan) 160 mg for 10 weeks or taking lavender flower powder 1 gram daily for 2 months have not reported side effects of drowsiness, sedation, or sleepiness (97256,103061). There is still some concern that higher doses or different preparations of lavender might have additive effects with CNS depressant medications.

(Read more about LAVENDER)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.  Details Research in animals and humans shows that passion flower has sedative effects which can be additive when used with sedative medications like lorazepam (8007,19235,19236,19429,68309,104206).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, passion flower might decrease the effects of CYP3A4 substrates.  Details In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer (110704).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.  Details In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition (105095). OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.

(Read more about PASSION FLOWER)

General ...Orally or topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about ALBIZIA JULIBRISSIN)

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, lavender is well tolerated in food amounts and seems to be well tolerated in larger amounts. Topically, lavender oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Breath odor, constipation, diarrhea, dyspepsia, eructation, headache, and nausea.
Topically: Allergic contact dermatitis (with lavender oil).
Serious Adverse Effects (Rare):
Topically: Cases of gynecomastia have been reported in prepubertal males using lavender oil.

Cardiovascular ...Orally, a specific lavender oil ingredient (Silexan) has been associated with palpitations (103061).

Endocrine ...Topical products containing lavender oil alone, including a product referred to as agua de violetas, or in combination with tea tree oil have been linked to at least six cases of gynecomastia when used in prepubertal males. In each case, gynecomastia resolved when the lavender oil products were discontinued. It is thought that the estrogenic and antiandrogenic activity of lavender oil and tea tree oil resulted in gynecomastia in these cases (15254,95643).

Gastrointestinal ...Orally, lavender oil, including a specific lavender oil ingredient KG), may cause gastrointestinal disturbance, including dyspepsia, diarrhea, breath odor, eructation, and nausea (58077,58080,58098,93004,103061). Tincture of lavender has been linked to cases of constipation and increased appetite; however, it is unknown if this occurred at a greater rate than with placebo (9792).

Immunologic ...Topically, use of lavender oil, such as in personal care products, might cause allergic contact dermatitis in some patients (6,101728). There have been numerous case reports of allergic contact dermatitis and eczema linked to lavender oil exposure from shampoos, lotions, fragrances, or direct application of oil to pillows (10031,58043,58109,58120,101728).

Neurologic/CNS ...Orally, lavender flower powder, tincture of lavender containing 50% alcohol, and a specific lavender oil ingredient (Silexan) have been linked to headache (9792,103061,109860). Headache has also been reported rarely following lavender oil aromatherapy (109860).

Pulmonary/Respiratory ...In one case report, a 34-year-old Japanese female presented with complaints of dyspnea, cough, and fever 2 weeks after initiating lavender essential oil therapy via humidifier. The patient had an oxygen saturation of 88% and was diagnosed with acute eosinophilic pneumonia. Symptoms improved after a course of corticosteroids and discontinuation of aromatherapy (109979).

(Read more about LAVENDER)

General ...Orally, passion flower is well tolerated.
Most Common Adverse Effects:
Orally: Confusion, dizziness, hypersensitivity, and sedation.

Cardiovascular ...There is a case report involving a 34-year-old female who was hospitalized with severe nausea, vomiting, drowsiness, prolonged QT interval, and episodes of nonsustained ventricular tachycardia following use of passion flower extract tablets (Sedacalm, Bioplus Healthcare), 1500 mg on day 1 and 2000 mg on day 2 to relieve stress. All symptoms resolved within one week after passion flower was discontinued (6251).

Genitourinary ...The alkaloids harman and harmaline, which are sometimes found in small amounts in passion flower, have been reported to have uterine stimulant activity (4,11020,95037).

Hematologic ...Orally, passion flower has been reported to cause epistaxis in one clinical trial (95038). Vasculitis has also been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).

Hepatic ...There is debate about whether passion flower contains cyanogenic glycosides. Several related Passiflora species do contain these constituents (3), including Passiflora edulis, which is associated with liver and pancreatic toxicity (7).

Immunologic ...An idiosyncratic hypersensitivity reaction characterized by urticaria and cutaneous vasculitis has been reported in a 77-year-old male with rheumatoid arthritis after taking a specific combination product that included passion flower extract (Naturest) (68308). It is unclear if these effects were caused by passion flower or other ingredients.
In clinical trials, passion flower has been reported to cause allergy symptoms including sinus irritation; however, the frequency of these events was statistically nonsignificant when compared to treatment with midazolam 15 mg (95038).

Musculoskeletal ...Orally, passion flower has been reported to cause muscle relaxation in a clinical trial (95038).

Neurologic/CNS ...Orally, sedation, dizziness, ataxia, and confusion have been reported in clinical trials. However, these events generally do not necessitate discontinuation (8007,15391,15392,95036,95038). Altered consciousness has been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).

(Read more about PASSION FLOWER)