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Home , Scutellaria, Scutellaria baicalensis, Scutellaria lateriflora

Research American skullcap ( laterifl ora): an ancient remedy for today’s ?

nxiety is ‘an unpleasant emotional state Abstract ranging from mild unease to intense fear’ Anxiety is a common but potentially serious disorder as it can lead to somatic and A(British Medical Association (BMA), 2002). social dysfunction. Orthodox are associated with unpleasant side-effects and Although anxiety is a normal response to stressful dependency. American skullcap (Scutellaria laterifl ora) is a popular in traditional situations it can be seen as a chronic manifestation medicine systems and the western materia medica for anxiety and related disorders. of a modern lifestyle that includes repeated daily Preliminary clinical and in vitro research provides encouraging support for its potential as a stressors (Pavlovich, 1999). It is a potentially serious safe, well-tolerated and effective alternative. disorder as it can precipitate a number of health problems and diffi culties in social and occupational functioning (Fricchione, 2004). Key points Physical symptoms of anxiety include pallor,  Research has demonstrated the capacity of American skullcap’s fl avonoids to bind to sweating, hyperventilation, diarrhoea, irritable brain receptors implicated in modulation of anxiety bowel, fl ushing, dysphagia, palpitations, nausea, and  In one year up to one in six UK adults in the UK may suffer from an unexplained muscle tension (BMA, 2002). Furthermore, Pitsavos psychological disorder, the most common being anxiety et al (2006) found strong evidence for a positive  Anxiety and stress are common reasons for visits to practitioners association between severity of state anxiety in both  An initial survey of UK and Ireland herbal medicine practitioners indicated American men and women and increased levels of plasma skullcap as their treatment of choice for anxiety and related disorders pro-infl ammatory cytokines, coagulation factors,  Quality control of the raw herb and its commercial products is important. C-reactive protein and white blood cells. Alleviation Key words of these adverse eff ects on health is important. Anxiety, Stress, Herbal Medicine, Many orthodox treatments can have unwanted side eff ects. , for example, have been linked to muscle weakness, article discusses its clinical application, and reviews Christine Brock amnesia, headaches, vertigo, urinary retention, both scientifi c and anecdotal evidence in support of Research scholar, slurred speech and gastrointestinal disturbances. its traditional use for anxiety. School of Life Sciences, They may lead to tolerance and physical and University of Westminster psychological dependence, and are considered American skullcap (Scutellaria to be dangerous to use long–term (BNF, 2008). laterifl ora L) Julie Whitehouse The side eff ects of antipsychotics, sometimes Scutellaria laterifl ora is a perennial herb belonging Principal lecturer and course prescribed in the short–term for severe anxiety, to the (mint) family and is one of 360 leader, include tremor, abnormal face and body movements known skullcap species worldwide (Malikov and School of Life Sciences, and restlessness (BNF, 2008). Beta-blockers may Yuldashev, 2002). It grows on wetlands and is University of Westminster be prescribed for relief of physical symptoms, indigenous to North America and Canada where such as tremors and palpitations, associated with it is widely distributed (USDA). It also grows on Ihab Tewfi k anxiety. However, side eff ects are similar to those riverbanks and marshes in northern Iran (Yaghmai, Course leader, of benzodiadepines and may additionally include 1988) and is grown commercially worldwide (Wills School of Life Sciences, bradycardia, vasoconstriction and heart failure (BNF, and Stuart, 2004). University of Westminster 2008). There is therefore a need for safe alternatives, It was an important North American without unwanted side eff ects. ethnobotanical medicine for use in anxiety, hysteria, To n y To we l l American skullcap (Scutellaria laterifl ora) (Figure phobias, panic attacks, tension, sleep disorders and Professor and course leader, 1) is one of the most commonly used by stress (Felter and Lloyd, 1898; Joshee et al, 2002). It Department of Psychology, western medical herbalists, particularly for anxiety has also been used for centuries in both Persian and University of Westminster and related conditions (Bergner, 2002–2003). This Cherokee folk medicine for nervous disorders of the

British Journal of Wellbeing • Vol 1 No 4 • July 2010 25 Research

conditions, and infl ammation (Natural Medicines Comprehensive Database, 2008). Following reports of liver damage from use of S. laterifl ora products there was a decline in its popularity in the 1970s and 1980s (McCaleb, 2004). The cause of the hepatotoxicity was probably due to contamination with Germander () species (De Smet, 1999), which contains pyrrolizidine alkaloids (McCaleb, 2004). S. laterifl ora is not associated with hepatotoxicity. Since 2002 there has been a sharp increase in demand for S. laterifl ora, possibly due to it being favoured as an anxiolytic alternative to the previously popular Piper methysticum ( kava), which, due to toxicity fears, is no longer widely prescribed by herbalists in Europe (Greenfi eld and Davis, 2004). (Georgi) (Baikal skullcap) root is extensively prescribed in traditional Chinese and Japanese (kampo) medicines. In particular, this is used to treat infl ammatory diseases, and has been widely researched in relation to its effi cacy and pharmacological properties. Although S. laterifl ora is a popular herb in western herbal medicine and is contained in many herbal formulations (Joshee et al, 2002), particularly for anxiety and stress, relatively few scientifi c studies of this herb exist (Cole et al, 2008). S. laterifl ora is the practitioner’s choice for treating anxiety Results of a survey conducted by the authors among herbal medicine practitioners in the UK and Ireland indicate that S. laterifl ora is considered to be an eff ective intervention for anxiety and stress

USDA NRCS WETLAND NRCS USDA INSTITUTE SCIENCE and is commonly prescribed for these conditions life: Scutellaria laterifl ora L. and related co-morbidities. digestive tract (Khosh, 2000) and Native American The survey aimed to gather information on women traditionally used it for premenstrual tension the extent of, and indications for, current use (Indiana Medical History Museum, undated). The of S. laterifl ora. It also looked at perceptions herb is also used extensively and highly valued of its eff ectiveness and safety. Herbal medicine in traditional western herbal medicine. It was practitioners were selected from the membership mentioned in the fi rst American materia medica in list of the National Institute of Medical Herbalists 1785 but had been in longstanding use as a home (NIMH). All members with identifi able email remedy before then (Lloyd 1911; 109). addresses were contacted (n = 377) and responses In modern western herbal medicine it is used were received from 62 (a 16% response rate). most commonly for insomnia, nervous disorders and Results indicate primary use of S. laterifl ora for digestive disturbances (Greenfi eld and Davis 2004). relief of anxiety, stress or associated symptoms. Bergner (2002–2003) proposes its action is primarily More than eight respondents in ten (84%) said they as a trophorestorative on the central nervous system, would prescribe it for specifi c anxiety disorders allowing relaxation following nervous exhaustion. and 100% for anxiety-related co-morbidities. It is also used for and tranquilliser Twenty fi ve respondents said it is their preferred withdrawal symptoms (Joshee et al, 2002), herb for anxiety (Figure 2). One respondent said fi bromyalgia, anorexia nervosa, post-stroke paralysis, his or her preferred anxiolytic was S. baicalensis. , hyperlipidaemia, allergies, skin In common with many other Scutellaria species,

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S. laterifl ora and S. baicalensis have similar about the perceived actions of S. laterifl ora used in phytochemical constituents, although in diff erent isolation. Nevertheless the practitioners appeared ratios and quantities. This may explain the diff ering confi dent about attributing specifi c actions and traditional uses among Scutellaria species. For responses to S. laterifl ora as distinct from other instance, S. baicalensis contains 800 times more herbs in a mixture in having the anxiolytic actions. than S. laterifl ora (Cole et al, 2008). Furthermore, respondents prescribing it as a single Although S. baicalensis is most commonly used for herb reported positive feedback from their patients. infl ammation (Joshee et al, 2002) both S. laterifl ora Examples include reduced anxiety, fewer and and S. baicalensis have been found to inhibit less intense panic attacks, feeling of wellbeing, cyclooexgenases in vitro (Gafner et al, 2004; Jia feeling more positive, and more able to cope. et al, 2007). S. laterifl ora is reported to have been Interestingly, one practitioner prescribing the herb traditionally used for infl ammation. The Iroquai in combination reported a relapse in symptoms of tribe, for example, used it ‘to keep the throat clear’ anxiety in some patients whenever it was removed (Joshee et al, 2002). Conversely, S. balicalensis root from the mix. is reported to have been used as a (Liao et The herb was reported as being well tolerated al, 1998). with no reports of toxicity and only minor and All respondents who regularly prescribe S. infrequent side eff ects (reported by seven users). laterifl ora (92%) said they did so for anxiety. Some These included daytime drowsiness, mild digestive reported it useful in depression (16%), while several upset and vivid dreaming. It is uncertain whether respondents said it was unsuitable for signifi cant any of these side eff ects were in fact due to S. depression. laterifl ora. Use for insomnia and sleep-related disorders It is recognised that the response rate (16%) was specifi cally reported by 57% of respondents. was low and that all the survey respondents Other conditions for which it was used include fear replied to email contact and therefore may not be and panic states, migraine and other headaches, representative of herbal practitioners in general muscular tension, physical and mental exhaustion in the UK and Ireland. The poor response rate and post viral fatigue. Three practitioners also and the propensity of respondents to administer said it was useful in emotional disturbance in S. laterifl ora in combination with other herbs menopause and in cases of premenstrual syndrome. make it impossible to rely on evidence regarding The survey respondents reported the herb as the effi cacy of the herb from the practitioner being used over a range of time periods from immediate short–term use to several years. They Figure 1. Anxiolytic herbs as preferred by survey respondents said a positive response was expected by patients within the fi rst two weeks of use and that this 25 persists throughout the period of use. The most common benefi ts reported by patients 20 to their practitioners were feeling calmer, improved sleep patterns and quality of sleep, and better able 15 to cope in stressful situations. Other positive eff ects were mood elevation, increased energy, being more 10 focused and feeling generally more relaxed. Tinctures made from either fresh or dried organic

Number of times chosen Number of times 5 and non-organic herb are the preferred mode of administration by respondents. The main reason is a belief that tinctures are more eff ective, are 0 better for patient compliance and are generally Tilia Avena None Piper Melissa Stachys Verbena more convenient than dried herbs. Many (63%) LeonorusMatricaria Passifl ora Valeriana CrataegusHypericumLavandula S.laterifl ora said they prefered using organic S. laterifl ora, while S.baicalensis 42% preferred tinctures made from the fresh herb, Preferred herb for anxiety believing this to be the most eff ective. Key: Avena = A. sativa (oats); Crataegus = Crataegus spp. (hawthorn); Hypericum = H. perforatum (St John’s wort); All respondents prescribe the herb in = Lavandula spp. (lavender); Leonorus = L. cardiaca (motherwort); Matricaria = M. recutita (German combination with other herbs. Only 9% of the chamomile); Melissa = M. offi cinalis (balm); None = no preference; Passifl ora = P. incarnata (passion fl ower); Piper = Piper methysticum (kava-kava); S. baicalensis (baikal skullcap); S. laterifl ora (American skullcap); Stachys = S. respondents regularly prescribed S. laterifl ora as betonica; Tilia = Tilia spp (linden); Valeriana = Valeriana offi cinalis (); Verbena = Verbena offi cinalis (vervain). a single herb so it is diffi cult to draw conclusions

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survey alone. A future survey could include herbal The potential effi cacy of S. practitioners from other professional bodies such laterifl ora in treating anxiety as the Council of Practitioners of Phytotherapy. In addition, contact with herbalists internationally Chemistry may provide a more useful indication of the S. laterifl ora is rich in fl avonoids, a group of phenolic benefi ts of the herb. compounds that are highly active physiologically, and have been attributed with its anxiolytic eff ects. Preparations and dosages used , its aglycone , and Preparations of S. laterifl ora are made from the laterifl orin are the major fl avonoids in S. laterifl ora aerial parts and are sold in the form of tinctures, (Nishikawa et al, 1999; Gafner et al, 2000; Gafner et teas and tablets; and capsules containing powders, al, 2004). liquids or freeze-dried material. Dosages vary It also contains γ-aminobutyric acid (GABA), an according to extraction, marc: menstrum ratio, inhibitory neurotransmitter that modulates anxiety, practitioner preference and preparations used sleep, convulsions and mood (Rabow et al, 1995), but average at around Ig equivalent dry weight and markedly high levels of , a non- per dose three times daily (Natural Medicines essential amino acid that plays an important role in Comprehensive Database., 2008). Preparations immune function—particularly in response to stress from fresh herb are thought to be most eff ective (Bergeron et al, 2005). Although GABA does not (Felter and Lloyd, 1898; Kuhn and Winston, 2001; readily cross the blood-brain barrier (Spinella, 2002), Yarnell and Abascal, 2001). glutamine can and may be biosynthesised to GABA by GABA-ergic neurons. The presence of glutamine Contraindications and side- in the herb may therefore contribute to its anxiolytic effects activity by increasing the availability of GABA in the Due to its potential sedative action (Greenfi eld central nervous system (Bergeron et al, 2005). and Davis, 2004), it may be advisable to refrain from using S. laterifl ora in combination with other In vitro studies , such as and benzodiazepines. It Benzodiazepines are allosteric ligands for the

is not possible to comment on the safety of its use GABAA receptor, a chloride channel that is gated by in pregnancy. GABA. They bind to the site of the

GABAA receptor, thus increasing the affi nity of the Anxiety: the demand for herbal inhibitory neurotransmitter GABA for the GABA site

treatment of the GABAA receptor. This decreases the likelihood In one year up to one adult in six in the UK suff ers of action potentials by excitatory neurotransmitters from a medically unexplained psychological (Rabow et al, 1995). One important study (Liao et al, disorder. The most common are anxiety (men 4%; 1998) indicated , baicalein and wogonin, women 5%), depression (men 2%; women 3%) which are fl avonoids found in S. laterifl ora, had

or both experienced at the same time (men 7%; weak affi nities for the benzodiazepine site of GABAA women 11%). These fi gures indicate that anxiety receptors in mouse cerebral cortex in vitro. In and depression are more prevalent in women another study Hui et al (2000) tested the capacity than in men (Offi ce for National Statistics, 2006). of baicalin, baicalein, and wogonin

Herbal medicine is used more frequently by women to bind to the benzodiazepine site of the GABAA than by men (Gunther et al, 2004) and, according receptor in homogenised rat brain. Affi nity to the to a survey in the United States (del Mundo et al, benzodiazepine site for scutellarein was moderate 2002) around 30% of visits to a complementary and and weak for baicalin. Contrary to results of the alternative medicine (CAM) practitioner were for earlier study (Liao et al, 1998), the binding affi nities anxiety and/or stress. Of 664 respondents (74% of of wogonin and baicalein were strong. The authors whom were females), only back pain was a more suggested the discrepancy may be due to diff erences common reason for CAM visits. As chiropractors in species and assay models used (Hui et al, 2000). were the most visited CAM therapists, with medical The ability of the skullcap fl avonoids to bind

herbalists a close second, it may be deduced that to the benzodiazepine site of the GABAA receptor since the chiropractors are more likely to treat suggests an anxiolytic eff ect for S. laterifl ora but back pain, the majority of visits to herbal medicine studies on human tissue of neuronal origin are practitioners were by women with anxiety and needed to verify results. stress (del Mundo et al, 2002). Gafner et al (2003) found extracts of dried S.

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laterifl ora aerial parts and its fl avonoids baicalin, of S. laterifl ora. While orthodox medicine tends to scutellarin, wogonin, laterifl orein, ikonnikoside employ isolated phytochemicals, herbal medicine I and dihydrobaicalin, had high affi nity for the uses whole plant parts in the belief that there serotonin7 (5-HT7) receptor in human 5-HT7 - are synergistic benefi ts of the multiple active transfected Chinese hamster ovary cell lines. It was constituents in a single herb (Spinella 2002). It not known whether these extracts and fl avonoids is likely that the effi cacy of S. laterifl ora is due to were agonists or antagonists (Gafner et al, 2003), but its multiple constituents acting in synergy rather 5-HT7 receptor antagonists and inverse agonists are than to the summative activities of the constituent known to be useful in the treatment of premenstrual phytochemicals. There is still a need for more syndrome, sleep disorders, appetite disorders, research into the pharmacology of extracts from anxiety, phobias, panic, and stress-related disorders whole aerial parts of the herb and the variability (Bright et al, 2004); these are also conditions for which may arise from the herb sourced from which S. laterifl ora is traditionally used (Joshee et al, diff erent geographical regions. 2002; Greenfi eld and Davis, 2004). Conclusions Human clinical trials The traditional therapeutic uses of S. laterifl ora are To date only one clinical trial has been published supported by evidence from research. A positive on S. laterifl ora. Wolfson and Hoff mann (2003) therapeutic benefi t of the herb for anxiety is assessed its short–term anxiolytic properties in a indicated by the results of a survey conducted double-blind, placebo-controlled crossover study of among herbal medicine practitioners; in vitro 19 healthy volunteers. Participants took either two and chemical studies; and a clinical trial, which placebo capsules, one capsule containing 100 mg of supports its reputation for safety as well as its organic freeze-dried S. laterifl ora, two capsules of effi cacy as an anxiolytic. these, or one capsule of 350 mg organic freeze-dried As with all studies of herbal medicines important S. laterifl ora. Participants’ energy, cognition and considerations, which may impact on fi ndings, are anxiety were self-rated at various time points up to the variations in quality and quantity of any given two hours following administration. All three herb herbal preparation as well as the eff ects of other tests had notable eff ects on subjective anxiety scores herbs in a mixture. Commercial herbal products when compared to placebo. There was only a very have been found to contain signifi cant variations mild decline in cognition and energy with the herbs, in phytochemical profi le within a species. Such with no adverse reactions or side-eff ects, suggesting variation may be according to geographic region, that S. laterifl ora could be a valuable anxiolytic biodiversity, ecological variations, cultivation, (Wolfson and Hoff mann, 2003). seasonality, harvesting, processing method, and More research needs to be conducted in order to marc to menstrum ratio. Alcohol concentration, assess long–term eff ects. Furthermore, the authors and storage time aff ecting stability are other factors acknowledge that the use of validated psychometric (Ciddi, 2006; Gao et al, 2008). Stability of a herbal tests is needed to determine the herb’s clinical product is important with regard to effi cacy and anxiolytic eff ects. safety and may be aff ected by various factors, such as pH, light, enzymatic degradation (for example Summary and evaluation of due to harvesting stress, heat or insects) and experimental results temperature (Gafner and Bergeron 2005). The receptor binding affi nities of fl avonoids present Furthermore, quality control of S. laterifl ora in S. laterifl ora, including baicalein, baicalin, is important to not only ensure high standards wogonin and scutellarein, to GABAA-BDZ receptor of effi cacy but also for reasons of safety. It is sites in vitro (Liao et al, 1998; Hui et al, 2000) frequently adulterated with germander species indicates a possible anxiolytic action for the herb or other skullcap species, both deliberately as does the presence of glutamine and the ability (germander has a heavier dry weight) and due to of certain S. laterifl ora fl avonoids to bind to 5HT7 misidentifi cation of the large number of skullcap receptors in vitro (Gafner et al, 2003). The results species (Gorman, 2008). High Performance Liquid of a survey among herbal medicine practitioners Chromatography (HPLC) methods can be used to on their use of the herb and of a clinical study lend verify its purity and quality. A characteristic profi le further support to its eff ectiveness as an anxiolytic. of the HPLC chromatogram or ‘fi ngerprint’, which The majority of in vitro fi ndings are as a result of is altered by adulteration, can be used for accurate research conducted using individual phytochemicals identifi cation of the herb. The pattern’s relative

British Journal of Wellbeing • Vol 1 No 4 • July 2010 29 Research

percentage of fl avonoids is the key point to ascertain depression. Ultimately it may emerge as a useful and the quality and identity of S. laterifl ora (Wills and cost-eff ective agent to rival currently used anxiolytic Stuart, 2004). pharmaceuticals. BJW While the results of the in vitro and chemical studies are interesting and provide clues to the pharmacological action of S. laterifl ora, more clinical studies are required to provide better evidence of the therapeutic value of Scutellaria laterifl ora as Acknowledgements an eff ective agent for anxiety and stress. It has the Thanks to the herbal medicine practitioners who gave potential to be as important for the treatment of up their valuable time to respond to the skullcap survey anxiety as St John’s Wort has been found to be for

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