Anxiety Disorders: Supplements With Possible Efficacy

2015

In addition to supplements discussed above, a few other compounds may also have some efficacy in treating symptoms of anxiety. However, since the data that supports the use of the following supplements is extremely limited, clinicians should proceed with caution, and consider the use of the compounds discussed in this section as experimental.

St. John’s Wort

As described in site, St. John’s Wort (Hypericum perforatum) is an herb that exists in many species throughout the world, and it is widely used as an antidepressant. It is available in a variety of preparations, including capsules, liquid, oils, and raw herb to be brewed as tea. St. John’s Wort contains a plethora of active ingredients, including flavonoids, naphthodianthrones, phloroglucinols, phenolic acids, terpenes, and xanthones. These exert a variety of psychoactive effects, and several of these are described below.

Of all herbal supplements, St. John’s Wort is the one that has been researched most extensively and there is strong support for its efficacy in reducing depressive symptoms. The use of St. John’s Wort as an anxiolytic is more recent, but a few studies suggest that is may be effective. Davidson and Connor (2001) reported case studies of patients with generalized anxiety disorder who responded well to St. John’s Wort at doses of 900mg twice daily (BID), and tolerated it with minimal side effects. Improvement was seen in about 4 weeks and after using the compound for a year, patients continued to exhibit clinical improvement without adverse effects or relapse. A similar study was performed with patients with obsessive compulsive disorder and found that after 3 months of treatment, patients exhibited significant clinical improvement. Thus far, there appear to be no studies that investigated the use of St. John’s Wort with children or adolescents with anxiety disorders.

Because of the plethora of active ingredients, the mechanism of action of St. John’s Wort is very complex. Its antidepressant effects are likely secondary to weak monoamine oxidase inhibition (MAOI), as well as catechol-O-methyl transferase (COMT) inhibition, and collectively these effects may contribute to higher levels of monoamines in the brain. Its anxiolytic effects may be related to agonist activity at GABA benzodiazepine receptors, serotonin reuptake inhibition, and activation of mu and kappa opioid receptors. All in all, it is likely that various ingredients are responsible for the anxiolytic effects of St. John’s Wort, and utilizing the whole plant with its multiple constituents may have a synergistic effect.

St. John’s Wort is absorbed from the gastrointestinal tract and the most active ingredients are lipophyllic, aiding its absorption. Hyperforin reaches maximum plasma levels in about 3 hours, and hypericin reaches these levels in about 4 hours. Half-life for hyperforin is about 9 hours, but the half-life for hypericin is much longer and may reach 24 hours. Long-term dosing of 300 mg three times per day (TID) revealed that steady state was reached after 4 days of treatment.

St. John’s Wort utilizes the CYP450 enzyme system for metabolism, but the exact pathways have not been identified thus far (Medical Economics, 2007). However, the herb exerts significant effects on liver metabolism. While the ingestion of the herb appears to induce liver metabolism, perhaps by inducing P-glycoprotein, hyperforin has also been found to significantly induce CYP 3A4 enzyme. Because this enzyme is responsible for the metabolism of many medications, the use of St. John’s Wort with prescription medications should generally be avoided.

For adults, the standard dose is 300mg, and because of hyperforin’s short half-life, the herb must be taken three times per day (TID). Usually, it is recommended that standardized extracts with 0.3 percent hypericin should be used (Medical Economics, 2007). In children, the usual starting dose in 150mg TID, and the dose is gradually increased until about 900mg/day in teenagers, although lower doses in younger children, and higher doses in mature teens may be needed.

St John’s Wort is generally well tolerated and minimal side effects are reported. Sometimes, gastrointestinal irritation, nausea, constipation, and feeling of uncomfortable fullness has been reported (Medical Economics, 2007). Usually, taking the compound with food may reduce these difficulties. Fatigue and/or restlessness has also been reported in some cases. Frequent urination has also been reported.

Photosensitivity has been reported with the use of this compound. This means that some individuals who take the herb become more sensitive to sunlight and may easily experience sunburns. The mechanism of this problem is attributed to increased sensitivity to ultraviolet waves (UVA and UVB). Patients who take St. John’s Wort should be monitored for this reaction and, if one is observed, use of sun blocking sunscreens will be necessary. For children and adolescents who spend a lot of time outside, this problem must especially be monitored.

St. John’s Wort is contraindicated during pregnancy due to evidence of damage to reproductive cells (Medical Economics, 2007). Female adolescents who take St. John’s Wort and are suspected of being sexually active must be advised of this risk, and should use contraception to prevent pregnancy. However, oral contraceptives are metabolized by the same CYP 3A4 pathway that is induced by St. John’s Wort, and breakthrough bleeding and pregnancy have been reported as a result of the increased metabolism of oral contraceptives. Sexually active females must be aware of this risk and utilize other forms of birth control.

Cardiovascular effects have been reported in a minority of patients, and these may include swelling and an increase in heart rate. Even more importantly, a small risk of hypertension appears to be present in some patients. Although MAOI activity appears to be a minor component of this herb’s pharmacodynamics, it may pose some risk that is similar to prescription MAOI medications. Patients who take MAOIs must avoid products that contain tyramine, because decreased regulation of the MAO enzymes may lead to excess levels of noradrenaline, causing unsafe levels of blood pressure. Foods rich in tyramine include most aged food products, including cheese and aged meats, and tyramine-rich food products are plentiful in the typical American and European diet. The exact degree of this risk is not yet known, and thus far only one case has been reported that presented with a hypertensive crisis potentially due to St. John’s Wort (Medical Economics, 2007). However, clinicians should use caution and monitor the blood pressure of patients who take St. John’s Wort (especially after meals), at least in the initial phases of treatment.

Perhaps the greatest risk associated with the use of St. John’s Wort is its effect on the liver, and the resultant potential for significant drug interactions. Generally, St. John’s Wort should not be utilized whenever patients take prescription medications. Of particular concern are protease inhibitors, anticoagulants, anticonvulsants, antiretrovirals, immunosuppressants, cardiovascular drugs, and anticancer drugs (Medical Economics, 2007). This list is by no means exhaustive. Usually, a 14 day washout period is often recommended when stopping or starting St. John’s Wort.

Although a specific ‘black box’ warning that applies to all antidepressants is not issued for St. John’s Wort, because of its antidepressant action, St. John’s Wort may be associated with a small increase in suicidal tendencies in those patients who present with symptoms of depression. Clinicians should carefully monitor patient response and intervene if an increase in suicidal thoughts or plans becomes evident. In addition, St. John’s Wort is also associated with a small risk of inducing hypomanic or manic symptoms, and some patients who have tendencies toward symptoms of bipolar disorder may exhibit ‘switching’ from depressive to manic symptoms. Once again, careful monitoring of dose/response and adverse effects is necessary.

Tryptophan and 5-Hydrohytryptophan

Tryptophan, also referred to as L-tryptophan, is an essential amino acid. Of all essential amino acids, it is the one that is least abundant. It is a protein with many functions in the body, and it is a building block for many endogenous substances. It is also a precursor for serotonin. Consequently, it has been researched as a hypnotic and an antidepressant.

Supplementation with tryptophan has been attempted for many years, and studies report inconsistent results. Because it competes to cross the blood-brain barrier, levels of tryptophan seem to be unpredictable and the response does not appear to be uniform. However, a modified version of tryptophan, 5-hydroxytryptophan (5-HTP) appears to cross the blood-brain barrier less competitively and seems to show more promise in results of research studies.

Some open and controlled trials reveal that tryptophan and 5-HTP may offer some benefits to treat symptoms of anxiety. Kahn and Westenberg (1985) performed a small, open trial and found that 10 patients with anxiety disorders treated for 12 weeks with 300mg/day of 5-HTP (with 50 mg of carbidopa TID) exhibited significant reductions in anxiety. The authors then performed a double-blind study with 45 patients and found that the group taking 5-HTP exhibited similar reduction in anxiety to the group taking clomipramine, a tricyclic anxiolytic. Other research also reveals that supplementation with tryptophan and/or 5-HTP is effective in patients who are described as ‘low serotonin producers’. Consequently, it is reasonable to expect that supplementation with tryptophan or 5-HTP may offer some benefits in reducing symptoms of anxiety.

In neurons, tryptophan is converted into 5-HTP, which is then further converted to serotonin (5-hydroxytryptamine, or 5-HT). Theoretically, supplementation with either should increase levels of serotonin in the brain, but because of the blood-brain barrier competition mentioned above, supplementation with 5-HPT seems to increase synaptic levels of serotonin more effectively. Increase in serotonergic activity is associated with the anxiolytic effects of medications such as SSRIs and some TCAs, and consequently the pharmacodynamics of the anxiolytic mechanism of 5-HTP may involve similar effects of serotonergic activity agonism, although 5-HTP seems to accomplish this by increasing the availability of the precursor, rather than the reuptake inhibition mechanism utilized by prescription anxiolytics (SSRIs and TCAs).

Following ingestion, tryptophan is absorbed from the small intestine and metabolized in the liver. However, 5-HTP is more easily transformed into serotonin in the small intestine, and therefore to prevent this effect, carbidopa is sometimes taken with 5-HTP to delay its demabolism. The portions not synthesized during first pass effect enter systemic circulation and become distributed to the brain and other tissues. The half-life of tryptophan and 5-HTP is presumed to be very short due to its rapid conversion into serotonin, and appears unrelated to the duration of the clinical effect, since anxiolytic action is likely due to the increase in serotonin.

Tryptophan tablets are generally available in tablets and capsules with dosages ranging from 50-1000mg, and 5-HTP is dosed similarly. Because research studies identified a very wide range of effective dose, trial and error is likely to be necessary to determine the appropriate dose for a specific patient. Children and adolescents should begin with a dosage of 50-100mg and the dose should gradually be titrated until clinical response is evident. Doses above 1000mg/day should only be used under medical supervision.

Tryptophan and 5-HTP are usually well tolerated, although some patients may exhibit daytime drowsiness, dizziness, and dry mouth. At higher doses, additional problems with nausea, lack of appetite, and headaches may become evident (Medical Economics, 2007). Because tryptophan and 5-HTP may exert sedative effects, concurrent use of other compounds that exert similar effects (for example, alcohol) should be avoided.

Tryptophan and 5-HTP are associated with a small risk of cardiac dysfunctions. Because tryptophan is converted into serotonin in the brain as well as peripherally, increases in serotonin may become evident in tissues and muscles, including the heart. When taken with carbidopa, these effects are not seen.

Tryptophan and 5-HTP need to be used cautiously with patients who have been diagnosed with diabetes or exhibit family history of diabetes. One of tryptophan’s metabolites, xanthurenic acid, has been found to have a diabetogenic effect in animals. Although no cases in humans have been reported, caution should be exercised.

Valerian

Valerian (Valeriana offlcinalis) is a medicinal plant endogenous to Europe and Asia and widely introduced in North America. Various portions of the plant are consumed for medicinal reasons, including the flowers, fruit, and leaves. However, it is valerian root that is considered to be most psychoactive and its extracts are used as hypnotics and anxiolytics. Although its use as a hypnotic is well supported, there is some research that also confirms its usefulness as an anxiolytic.

In one German study, 49 patients with anxiety responded to valerian and found it efficacious at a level similar to diazepam (a prescription benzodiazepine anxiolytic, sold in the US as Valium), and valerian was perceived to be superior when considering the risk-benefit ratio. Similarly, Leuschner et al. (1993) found valerian approximately equal in efficacy to diazepam or chlorpromazine (an anxiolytic neuroleptic). A more recent trial also revealed that valerian was effective in reducing symptoms of anxiety in patients with adjustment disorder with anxious mood. These findings are preliminary, but suggest that valerian may offer some benefits in treating symptoms of anxiety.

Like most herbal compounds, valerian may have as many as 150 individual compounds. Consequently, its action is likely to be very broad. Although the effects of the specific constituents have not been identified, the overall effect of supplementation with valerian is the depression of central nervous activity that may be due to changes in the affinity of cortical membrane receptors, including hyperpolarization. This is probably the result of changes in the activity of GABA, the major inhibitory neurotransmitter in the brain. As GABA levels increase, chloride channels on cell membranes open and the cells become hyperpolarized. Valerian increases activity of GABA in a variety of ways. Valerian may block, and perhaps reverse, the reuptake of GABA, thus increasing synaptic concentrations of GABA. In addition, valerian may also inhibit the metabolism of GABA, and may even act as a precursor for GABA synthesis. Just as is evident in the action of benzodiazepines, as GABA activity increases, anxiolytic effects become apparent.

Valerian is supplied in capsules, tablets, and liquid preparations, as an extract to be taken as drops (in a base, as in apple sauce) or dissolved in a tincture. Liquid preparations are absorbed more quickly, and tablets and capsules may take about 30-60 minutes longer to be absorbed. Pharmacokinetics are not well established, but onset of effect is generally seen in less than 1 hour. Various compounds present in valerian are metabolized through different mechanisms and at different rates, further complicating its use. However, it is apparent that clinical effects generally wear off after about 4-6 hours. Moreover, some have suggested that continued use of valerian, at the effective dose, does not result in tolerance to the effect.

When used with adults as a hypnotic, daily doses range from 100-1800mg, depending on the method of ingestion and the amount of the active compounds present in preparations available from different manufacturers. Studied dosages range from 1.5-3 g of actual herb or root, or 400-900 mg of an extract, taken up to 1 hour before bedtime. Bezchlibnyk-Butler and Jeffries (2007) recommend a dose of 200-1200 mg/day (with adults). With children and adolescents, about 20mg/kg is used for hypnotic effect. Usually, when used as an anxiolytic, lower doses are utilized to prevent sedation. Thus, it is apparent that the lowest possible dose should be started and dosage should gradually be titrated. Doses above to 20mg/kg/day ratio should only be used under medical supervision.

Valerian is usually well tolerated, although a minority of patients may exhibit some adverse effects. Some patients may report some gastrointestinal discomfort and headaches, as well as feeling of restlessness and heart dysrhythmias. These are generally more common with higher doses or when the compound is used for extended periods of time, but individual patient response should carefully be monitored. At higher doses, additional problems may become evident, including severe headaches, nausea and vomiting, dizziness, stupor, and cardiac dysfunction.

Valerian is associated with a small risk of hepatic damage. This risk is significantly increased when patients already take medications or other supplements that carry a similar risk. For this reason, use of valerian with other supplements should generally be avoided, unless the other supplement has no documented risk of hepatotoxicity. Use of valerian with medications should only be done under careful medical supervision. Even when valerian is used in monotherapy, some recommend periodic liver function tests to monitor the health of the liver.

Because valerian is a sedative, concurrent use of other compounds that exert similar effects (for example, alcohol) should be avoided. Because alcohol also exerts liver effects, it is especially important to make sure that patients who take valerian do not drink alcohol. While this is not usually a risk for children, this needs to be stressed when valerian is used with adolescents.

Valerian may interfere with the absorption of iron. For this reason, those who require iron supplementation should not take the two compounds together, and should take iron at other times of day (Medical Economics, 2007).

Theanine

Theanine, also known as L-theanine, is a non-protein amino acid mainly found naturally in green tea (Camellia sinensis) and some mushrooms (Boletus badius). Theanine is related to glutamine, is speculated to increase levels of GABA, serotonin, and dopamine. Theanine may also interact with Kainate and NMDA receptors for glutamate. Theanine has been available in Japan as a nutritional supplement marketed to reduce stress, produce feelings of relaxation, and improve mood. Recently, theanine has also been marketed in the US.

Anxiolytic effects are presumed but not well documented. In animal studies, theanine has been shown to stimulate GABA (A) receptors, and oppose caffeine stimulation. Studies in humans are more rare. In one study, Lu et al. (2004) found theanine to be as effective as alprazolam (a benzodiazepine anxiolytic, sold in the US as Xanax) in improving a sense of relaxation. A subsequent study confirmed these effects and found theanine to be effective in reducing the physiological effects of the stress response and the psychological experience of anxiety. Although theanine is generally well tolerated, use of theanine in the pediatric population is considered experimental and clinicians must proceed with much caution.

Theanine supplements are generally available as tablets and capsules in doses between 50 and 200mg. Although theanine is present in most green teas, the amount is unpredictable. Generally, two to three cups of green tea may contain between 30 and 50mg of theanine (Medical Economics, 2008), but this depends on the specific leaves being used and the brewing method. For this reason, it is best to avoid using theanine in tea when clinical effects are desired. Anxiolytic effects in adults are usually seen with doses of 200mg/day (2.3mg/kg/day). Pharmacokinetics are not well established, but theanine appears to be absorbed from the small intestine. Peak blood levels are reached between 0.5 and 2.0 hours after consumption. Theanine crosses the blood-brain barrier and may be taken up by the cells via a sodium-coupled active transport process. No guidelines about effective dosage ranges have been established.

Theanine supplements are usually well tolerated and no adverse effects have been reported thus far. However, pregnant and nursing mothers should avoid using the supplement. Female adolescents who take theanine and are suspected of being sexually active must be advised to use contraception to prevent pregnancy.

Ginger

Ginger (Zingiber offlcinale) is a tropical perennial that grows in Asia, west Africa, and the Caribbean. Ginger is well known as a spice, but its medicinal uses date back thousands of years. Ancient Greeks and Romans imported ginger from Asia, and it was known in China in the fourteenth century be. It is even mentioned in the Koran as a divine drink. More recently, it is recognized in the world for a variety of medicinal properties, including antiemetic, anti-inflammatory, antimicrobial, antioxidant, antithrombotic, cardiotonic and antimigraine effects, and it is approved by Germany’s Commission E as a treatment for loss of appetite, travel sickness, and dyspepsia (Medical Economics, 2007).

Ginger has several active constituents, including aromatic ketones and terpenoids, and some of these may have anxiolytic properties. These psychoactive effects may be secondary to the inhibition of 5HT 3 receptors, as well as eicosanoid inhibition, which results in greater GABA activity. GABA conductance may further be increased by inhibition of arachnoid acid metabolites. In addition, abnormally higher levels of cortisol are usually released during stress reactions, and studies have shown that levels of cortisol reduce after ginger supplementation. Results of animal studies confirm ginger’s anxiolytic properties, and ginger is often used in Ayurvedic medicine to treat symptoms of anxiety. Because ginger is well tolerated and poses very few risks, careful supplementation in children and adolescents may be warranted.

Ginger supplements are available in tablets and capsules ranging from 100-1000mg. Chewable tablets are also available, and liquid and tea bags preparations may be obtained. Generally, the use of tablets and capsules is recommended because it is easier to control the dosage. In some studies, higher doses of ginger taken on an empty stomach were associated with the development of ulcers, and therefore it is recommended to take ginger supplements with a meal. Very little is known about pharmacokinetics of ginger, but animal studies suggest that following absorption and systemic distribution, it is rapidly cleared. However, serum binding was equally rapid, especially for one of the gingerol ketones. At least some of the constituents of ginger are metabolized by the liver, and cross-metabolism of some of the constituents into others also seems evident.

When used to treat nausea, dyspepsia, motion sickness, or arthritis, dosage generally range from 0.5-4 g/day. This can be converted to approximately 5.8-46.5mg/kg/day. Children and adolescents should be dosed toward the lower end of this ratio, and gradually titrated while monitoring response and adverse effects. According to available data, ginger has a very wide therapeutic window and lethal doses have been reported to range from 250-680mg/kg (Medical Economics, 2007). It is clear that the clinical range is a tiny fraction of this dose.

In doses listed above, ginger is generally well tolerated and adverse effects are rare. Some patients experience mild gastrointestinal distress, flatulence, bloating, and heartburn. In higher doses, some patients have experienced dermatitis, cardiac arrhythmias, and central nervous system depression.

According to Germany’s Commission E, ginger is contraindicated during pregnancy. However, research studies failed to reveal any difficulties of malformations in the fetus, and ginger is sometimes used as an effective remedy for morning sickness (Medical Economics, 2007).

The use of ginger with some medications should be avoided. Concurrent use with anticoagulants may increase the risk of bleeding, and therefore the use of the supplement with any medications that decrease platelet aggregation should only be done under monitoring by medical professionals.

Taurine

Taurine is a non-protein organic amino sulfonic acid mainly found naturally in meat, fish, eggs, and milk. Humans also produce it from cysteine, but infants and children do so in much lower amounts, and some children lack the enzyme necessary for its metabolism. For this reason, taurine is added to most baby foods, as it is presumed to be necessary for normal retinal and brain development. Taurine has membrane stabilizing effects and consequently, as discussed in Chapter 7, it has been presumed to be involved in regulating neurotransmission and may have some efficacy in reducing symptoms of mania. It has also been suggested that it may have anxiolytic properties by altering the activity of the inhibitory glycine receptors, and animal studies confirmed this effect. Taurine also seems to have an agonist effects on GABA A receptors. Case studies in women support anxiolytic effects when taurine is used at a dose of about at 1000mg/day, and findings of controlled studies in humans reveal that taurine inhibits the release of norepinephrine, which may have antihypertensive as well as anxiolytic effects. Although these findings are preliminary, taurine supplementation has been shown to be safe over a wide dosage, and therefore a cautious trial in the pediatric population may be indicated.

Taurine is absorbed from the small intestine and enters the brain through sodium and chloride dependent transport systems. In the cell, taurine may keep potassium and magnesium inside the cell while keeping sodium out. Thus, it may affect neuronal firing. Remaining taurine is conjugated to form the bile salts and is excreted into bile, where it is transported to the duodenum to take part in the metabolism of various lipids. Excess taurine is excreted by the kidneys.

Taurine supplements are generally available as tablets and capsules and clinical doses range from 500mg/day to 3g/day in adults (Medica Economics, 2008). Balch (2006) recommends a dosage of 500mg three times per day (TID) to treat symptoms of bipolar disorder. Taurine supplements are usually well tolerated and no adverse effects have been reported thus far. However, pregnant and nursing mothers should only use the supplement under medical supervision.

Passion Flower

Passion flower (Passiflora incarnata) is indigenous to many parts of the world, except Europe and Africa, although various species of passion flower have now been naturalized in those regions. Various species of passion flower are native to the US, especially the middle and southeastern regions of the country. Only a few species have psychotropic properties, including Passiflora incarnata, and perhaps P. coerulea and P. edulis (). Passion flower has long been used by Native American Indians for its sedative and anxiolytic effects. It is also recognized in other parts of the world for these properties. Passion flower is approved by Germany’s Commission E to treat nervousness and insomnia but, as discussed in Chapter 9, its hypnotic effects are not widely supported. As a supplement, passion flower is available in liquid and capsules.

Passion flower has many constituents, including flavonoids, maltol, and indole alkaloids. Active ingredients include chrysin, vitexin, coumerin, and umbelliferone. Chrysin is the most studied component. Along with other flavonoids, chrysin has been shown to bind to benzodiazepine receptors sites and acts as an agonist for GABA activity, especially at A type GABA receptors. This has an inhibitory effect on the brain, accounting for passion flower’s anxiolytic properties. In animal studies, psychoactive effects of passion flower were reversed by benzodiazepine antagonists, and the overall effect in the brain has been compared to that of diazepam (Valium).

Some studies began to confirm passion flower’s effectiveness as an anxiolytic in humans. Bourin et al. (1997) found that the herb was effective in reducing symptoms in patients with adjustment disorder with anxiety. Akhondzadeh et al. (2001) performed a small, double-blind, randomized study in which the effects of passion flower were compared with anxiolytic properties of oxazepam (a benzodiazepine). Results revealed similar efficacy and less adverse effects with the use of passion flower. Larzelere and Wiseman (2002) found similar efficacy when they reviewed a number of small studies, and a recent review in the Cochrane system revealed that studies are beginning to emerge that support its efficacy. Although no studies have thus far been performed with children or adolescents, supplementation with passion flower is regarded as safe and adverse effects are quite rare. Consequently, clinicians and parents may want to consider a cautious trial of passion flower to treat symptoms of anxiety.

Little is known about passion flower’s pharmacokinetics, but its half-life may be short because the supplement is generally taken two to three times per day. When brewed as tea, about 150 ml (1 cup) of boiling water is poured over about 1 teaspoon, of dried herb are brewed for about 10 minutes, and drunk two to three times per day (Medical Economics, 2007). When used in capsules, children and adolescents should start with a low dose (200 mg capsules seem to be the lowest available) and used twice to three times per day. Dosage may slowly be adjusted upward while monitoring response and adverse effects.

Passion flower is usually well tolerated and side effects are rare. When initiated, treatment with passion flower may exert sedative effects, so monitoring of response is necessary. Passion flower may contribute to blood thinning, so those who take anticoagulant medications should avoid using passion flower. This may include over-the-counter medications, such as aspirin and ibuprofen. Use of passion flower is contraindicated during pregnancy. Female adolescents who take passion flower and are suspected of being sexually active must be advised of this risk, and should use contraception to prevent pregnancy.

Chamomile

Chamomile, (Matricaria recutita) sometimes also referred to as German chamomile, is an herb that is native to Europe, Africa, and Asia, and is now also grown in North America. Chamomile has been used medicinally for thousands of years and was known by ancient Greek, Roman, and Egyptian cultures. It is now approved by Germany’s Commission E to treat cough and bronchitis, fevers, cold, inflammation, infection, wounds, and burns. It is available as a supplement in capsules, as well as tea bags and liquid extract.

Chamomile contains terpenoids, flavonoids, and lactones, including matricin and apigenin. Chamomile may have sedative effects because apigenin binds to benzodiazepine receptors and potentiates the activity at GABA A receptors. Apigenin also stimulates uptake of tyrosine, resulting in increased monoamine production. Apigenin may also inhibit the MAO enzyme, further increasing the availability of monoamines. Increase in serotonin may especially be related to its anxiolytic effects.

Animal models confirm that chamomile has anxiolytic effects, and a small number of case studies in humans also supports its sedative properties (Medical Economics, 2007), although its use as a hypnotic has been discredited. Because few risks are associated with its use, and the herb is usually well tolerated, a cautious trial in children and adolescents may be warranted.

Very little is known about the pharmacokinetics of chamomile. Doses in adults vary widely and range from 25 mg to 2000 mg per day. Half-life may be short because it is often recommended to take chamomile three times per day. Usually, chamomile is ingested when brewed as a tea and tablets are more difficult to locate, but may offer better dosage control. Liquid extract is generally dosed at l-4 ml three times per day (TID), and tincture is dosed at 15 ml three to four times per day (TID or QUID). Children and adolescents should start at low doses TID and gradually titrate upwards while response and adverse effects are carefully monitored.

Chamomile is usually well tolerated and side effects are rare. Patients with allergies to plants in the daisy family (including ragweed) should avoid chamomile because an allergic reaction may be triggered. When initiated, treatment with chamomile exerts sedative effects, so monitoring of response is necessary. Chamomile may contribute to blood thinning, so those who take anticoagulant medications should avoid using chamomile. This may include over-the-counter medications, such as aspirin and ibuprofen.

Use of chamomile is contraindicated during pregnancy because it may stimulate uterine contractions. Female adolescents who take chamomile and are suspected of being sexually active must be advised of this risk, and should use contraception to prevent pregnancy.