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Headache 2008 the Author Journal compilation 2008 American Headache Society

ISSN 0017-8748 doi: 10.1111/j.1526-4610.2008.01268.x Published by Wiley Periodicals, Inc.

Brief Communications
Response of Cluster Headache to Kudzu
R. Andrew Sewell, MD

Objective.To describe the self-treatment of cluster headache with kudzu. Background.Many cluster headache patients take over-the-counter (OTC) kudzu extract in the belief that it helps their cluster attacks. Kudzus actual efcacy has not been studied. Methods.A database of cluster headache patients was questioned about their use of various alternative remedies to treat their cluster headache. Of 235 patients identied, 16 had used kudzu, consented to interviews, and provided medical records. Results.In total, 11 (69%) experienced decreased intensity of attacks, 9 (56%) decreased frequency, and 5 (31%) decreased duration, with minimal side effects. Conclusion.Anecdotal evidence suggests that a component in OTC products labeled as kudzu may prove useful in managing cluster headache. This hypothesis should be tested with a randomized clinical trial. Key words: cluster headache, case series, kudzu (Headache 2009;49:98-105)

Cluster headache is a rare disorder, generally considered to be the most painful of all types of headache.1 It occurs predominantly in men (0.4% vs 0.08% of women), typically beginning in the third decade, and is categorized as either episodic, occurring for periods interspersed with pain-free remissions, or chronic, in which the headaches occur constantly for more than a year with no remission longer than one month.2 Ten percent of episodic cluster headaches ultimately evolve into the chronic form, and these are termed secondary chronic. In standard descriptions of cluster headache, an attack refers to the actual paroxysm of pain, a cluster period to a period of time when attacks occur regularly, and a remission
From the VA Connecticut Healthcare/Yale University School of MedicinePsychiatry, West Haven, CT, USA. Address all correspondence to R.A. Sewell, VA Connecticut Healthcare/Yale University School of MedicinePsychiatry, West Haven, CT 06516, USA. Accepted for publication August 2, 2008.

period to an interval during which no attacks occur.3 Cluster periods tend to recur at xed intervals ranging from several months to several years, often occurring at the same time each year, and are marked by recurrent stabbing attacks that increase in intensity over 5 to 10 minutes, last 15 minutes to 3 hours, and then fade away. Attacks typically occur 1 to 3 times a day, usually at strikingly predictable times (often 2 hours after the patient falls asleep) but can sometimes occur as often as every 2 hours. The intensity of the pain is severe enough that patients have been known to commit suicide.4 Standard care for cluster headache includes acute treatments such as triptans or high-ow oxygen taken at the onset of an attack, supplemented with prophylactic treatments such as verapamil or lithium, which are taken on a continuous basis once a cluster period has begun, or before sleep in order to prevent nocturnal attacks in the case of ergotamine.1 Unfortunately,
Conict of Interest: None

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Headache these treatments are rarely entirely effective and often have serious disadvantages. Triptans and ergot alkaloids often cannot be given frequently enough, and oxygen tanks are unwieldy and inconvenient. Many herbal remedies have been proposed to treat headache; of these, feverfew5 and cannabis6 have the most empirical support, but neither has been specically evaluated for cluster headache. Kudzu refers to any one of a number of vine species of the genus Pueraria that is indigenous to Asian countries, was imported to the USA in 1876, and has subsequently been used for green manure and fodder and as ground cover to prevent soil erosion.7 The use of Ge-gen (kudzu root) was described in the Chinese medical book Shang Han Lun Treatise on Fever 1800 years ago,8 and today its rhizome is a traditionally used component in Chinese medical polyprescriptions for liver diseases, strokes, and allergies. Kudzu contains antioxidants,9 has antipyretic and anesthetic effects,10 treats hypertension,11 dilates cerebral blood vessels, increases cerebral blood ow, and improves brain acetylcholine in a mouse Alzheimer model.12 Historically, it has had use in the treatment of alcohol-related problems since AD 600.13 Its use in the treatment of cluster headache has not previously been described.

99 treatments for cluster headache and phrased in such a way that kudzu did not appear to be a topic of undue interest. We restricted our analysis to the 16 (73%) individuals who (1) agreed to be contacted for evaluation by telephone or email; (2) met International Classication of Headache Disorders, 2nd edition, criteria for cluster headache; (3) allowed us to obtain copies of medical records documenting a diagnosis of cluster headache by an MD or DO. If the medical records did not support the diagnosis, the subject was excluded from further analysis.

METHODS The study was approved by the McLean Hospital/ Harvard Medical School IRB. A database of 235 cluster headache patients was surveyed via email on their use of a number of complementary and alternative remedies, including kudzu root. The subjects had been previously recruited for a study unrelated to kudzu14 and came from 3 sources members of the Clusterbusters patient advocacy group (37), respondents to an online survey about quality of life issues affecting cluster headache patients who had checked a box agreeing to be contacted for future research studies (189), and people who had heard on the Internet that we were studying cluster headache and independently emailed us asking to participate (9). As of October 10, 2006, 159 (68%) had responded; of these, 22 (14%) endorsed using kudzu root or extract to self-treat their cluster headache. Questions were asked on a variety of complementary and alternative

RESULTS Results are summarized in the Table. Of the 11 subjects with episodic cluster headache, 8 (73%) experienced a decrease in the intensity of their attacks, 7 (64%) experienced a decrease in frequency, 4 (36%) experienced decreased attack length, and 2 (18%) experienced a truncated cluster period. One subject experienced increased attack intensity, frequency, and duration. Of the 5 subjects with chronic cluster headache, 3 (60%) experienced decreased attack intensity, 2 (40%) decreased frequency, and 1 (20%) decreased attack duration, while 1 (20%) had increased attack intensity. Efcacy for cluster attack in this group showed a clear doseresponse relationship: 3 of the 4 treatment nonresponders were taking less than 1000 mg a day (total pill weight; actual dose of kudzu is substantially less), and only 3 of 7 (43%) patients taking kudzu less than 3 times a day showed benet. Of the 6 who reported no effects or worse effects from kudzu, all were taking it less than 3 times a day, whereas 8 of 10 (80%) taking the more frequent dose benetted (Fig. 1). Side effects were mild and infrequent, the most common being gastrointestinal effects experienced by 4 (25%). Measured by total dose per day, the effect of kudzu on cluster attack intensity, frequency, and duration also showed a doseresponse relationship, whereas its effect on cluster period length did not. In comparison, of the 36 (13%) respondents from the cohort of 285 in the database who endorsed using acupuncture, 4 (11%) felt it made their cluster headache worse, 7 (20%) felt it improved their cluster headache, and 21 (58%) reported no effect. Of the 58

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Table.Effect of Kudzu on Cluster Headache

Effect on attack Headache type 2 chronic Episodic Episodic 2 chronic 2 chronic Episodic Episodic Episodic Episodic 2 chronic Episodic Episodic 1 chronic Episodic Episodic Episodic 2 months 6 weeks 7 weeks 12 months 2 weeks 1 day 12 months 12 months 8 months 2 months 3 weeks 12 months 3 weeks 13 weeks 5 weeks 3 weeks Kudzu brand Dose (mg) Freq. Trial length Intens. Freq. Dur. Period length Side effects

No.

Age (years)

Sex

1 2 3 4 5 6 7 8 9 10 11 12 12 13 14 15 16

59 36 35 47 36 57 57 32 48 48 43 42

F M M F F M F M M M F M

40 31 49 32

F F M F

NW root PF PF NW PF NW PF PF PF NW NW PF NW NSI SW NH

613 ? 1500 1500 1226 1500 1226 1500 1500 1500 613 1226 1500 1226 650 800 100

Tid Bid Tid Tid Qd Qhs Tid Tid Tid Tid Bid Tid Bid Tid Qd-tid Qhs Qd

? ?

N/A N/A N/A ? N/A ? N/A

CNS GI GI GI GI, MS

= no effect; CNS = central nervous system; Dur. = duration; F = female; Freq. = frequency; GI = gastrointestinal; Intens. = intensity; M = male; MS = musculoskeletal; N/A = chronic cluster headache therefore no cluster periods; NSI = Neutraceuticals Science Institute; NW = Natures Way; PF = Planetary Formula; SW = StarWest Botanicals; NH = Natures Herb; 1 = primary; 2 = secondary.

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Fig 1.Percent of patients reporting improvement in cluster attack intensity, frequency, and duration and cluster period length, stratied by total daily dose of unstandardized extract consumed. A doseresponse relationship is apparent in kudzus effects on cluster attacks, but not on cluster period length.

(20%) respondents who endorsed using the water method drinking a glass of water every half an hour during the cluster period 3 (5%) felt it made their cluster headache worse, 16 (28%) felt it improved their cluster headache, and 37 (64%) reported no effect (Fig. 2). These data should not be construed as evidence of lack of efcacy of these 2 methods; rather, assuming that the effects of acupuncture and polydipsia on cluster headache are no different than placebo, then the reported efcacy of kudzu in this cohort is more than twice as great as would be expected from chance alone.

Fig 2.Subjective global effect of different alternative treatment modalities on cluster headache symptoms. There is no evidence to suggest that either acupuncture or polydipsia is more effective for cluster headache than placebo.

REPRESENTATIVE CASES (ALL OTHERS ARE INCLUDED IN APPENDIX A, AVAILABLE ONLINE ONLY) Case No. 2.A 36-year-old man with no other medical conditions had suffered from episodic cluster headache since age 16 years, characterized by 6 weeks of one or two 2-hour attacks per day separated by a 4or 5-month remission period. The attacks consisted of a boring pain in his temple and a knot in his neck, along with lacrimation, ptosis, meiosis, conjunctival injection, ushing, diaphoresis, and restlessness. Frequent absences caused problems at work, and the secondary depression and fatigue caused strain in his interpersonal relationships. He nds oxygen and sumatriptan to be effective abortive medications, and as prophylactic medication, he has tried propanolol and amitriptyline, which are ineffective, verapamil and psilocybin, which decrease the frequency and intensity of attacks, and prednisone, which stops the attacks only while he is taking it. When his last cluster period began, in June of 2005, he read on an Internet forum that kudzu treated cluster headache, so he decided to boil 1.5 ounces of dried kudzu root and drink it as a tea twice a day. Even though he was using no other medication, he suffered only 4 attacks during the entire 6-week cluster period, all mild. The cluster period was unchanged in length. He also had approximately 10 phantom attacks, a phenomenon he had experienced previously on verapamil. He was able to avoid taking all conventional prophylactic medication, and suffered no side effects from the kudzu other than vivid dreams. He does not smoke or use illicit drugs, but drinks 3 or 4 glasses of wine a week and 2 cups of green tea a day. Case No. 3.A 36-year-old man with no signicant medical conditions except for a history of benign familial infantile convulsions, which he had outgrown by age 3 years, started to have episodic cluster headaches at age 28 years and was correctly diagnosed at age 33 years. Each cluster period lasted 8 to 10 weeks separated by a remission period of 7 or 8 months, occurred usually in autumn or late February, and consisted of as many as 6 cluster attacks a day, at all times of day and night. Each attack was characterized by a

102 right-sided sharp boring pain radiating into his jaw and neck, sweating, ptosis and eyelid edema, conjunctival injection, rhinorrhea, phono- and osmophobia lasting 45 to 90 minutes. He coped well, suffering no job or relationship difculties as a result, but grappled with persistent fears that there was something deeply wrong with his brain. For 5 years he remained untreated, assuming that he had a sinus problem or simply trying not to think about it, and then started medication. Verapamil 120 mg a day decreased his attack frequency to once or twice daily, but did not decrease the attack intensity and caused him memory and coordination difculties. Valproate triggered 2 of the most painful and prolonged attacks he had ever experienced, so he discontinued it. Sumatriptan was an effective abortive, but side effects that included intensication and prolongation of subsequent attacks as well as a dull persistent ache at the site of the attacks the next day prompted him to discontinue it. In February 2005, he started to experience twinges in his right eye, heralding the beginning of a cluster period, and with his rst full-blown attack, he started on Planetary Formulas kudzu extract 1500 mg 3 times a day as well as a twice-daily multivitamin. To his surprise, he found that he experienced only 8 attacks for the remainder of the cluster period, which was half its usual length (only 7 weeks), no attack lasting longer than 30 minutes. The attacks differed from the usual although they still caused agitation and pacing, there were no associated autonomic symptoms, only pain, and the intensity of the pain was attenuated and these occurred only when he decreased the dose of kudzu to twice a day, forgot, or delayed a dose. He experienced no side effects. His next cluster period began with 4 times daily attacks in late November 2005, but he delayed taking kudzu until the intensity of the attacks became excruciating, in the second week of December, for fear that he would develop tachyphylaxis. Restarting a dose of Planetary Formulas 1500 mg 3 times a day, he found that his attacks diminished in both frequency and intensity to zero over the next 2 weeks, and the remainder of the cluster period passed asymptomatically until it ended in January.

January 2009 He smokes a pack of cigarettes every day, drinks one drink of alcohol every few months, and smokes cannabis roughly twice a year. He uses no other illicit drugs but drinks 4 to 5 cups of coffee a day.

DISCUSSION The putative mechanism of action by which kudzu might affect cluster headache should these results be veried is unclear. It is thought that the other therapeutic benets of kudzu are due to phytoestrogens, particularly isoavones, which possess both estrogenic and antiestrogenic properties, can act as selective estrogen receptor modulators,15 and have a long pedigree in the treatment of a number of disorders.16 Flavonoids are phenolic compounds widely distributed in plants, with over 4000 currently known.17 Their astringency probably repels insects, making isoavonoids the most important group of plant-protective phytoalexins.18 The isoavone puerarin, which is the principal component in kudzu,19 has hypoglycemic properties and increases coronary blood ow, reducing the frequency of acute angina events20 and normalizing endothelin, renin, angiotensin II post-myocardial infarction in 3 days.21 Puerarin attenuates mecamylamine-induced decits in inhibitory avoidance performance in rats, presumably through nicotinic-receptor agonism and N-methylD-aspartic acid (NMDA) agonism and serotonin decrease.22 It does not act as a beta-blocker or calcium antagonist, however.23 The 3 times daily dosing of kudzu that appears necessary to ameliorate cluster headache is consistent with puerarins pharmacokinetic prole.24 Daidzein is a metabolite of puerarin and daidzin, another isoavone in kudzu. Unlike daidzin and puerarin, daidzein scavenges free radicals25 and is estrogenic,26 albeit thousands of times less potent than the synthetic estrogen diethylstilbestrol. Estrogen and progesterone levels are normal in cluster headache, but the dramatically higher prevalence of the disorder in males, the increase in incidence around menopause,27 and the tendency of cluster headache to remit during pregnancy28 argue for a protective effect of female reproductive hormones that may be replicated by the phytoestrogens in kudzu.

Headache Kudzu has been reported to decrease alcohol intake in both preclinical29 and clinical trials. Investigators found that over-the-counter (OTC) preparations of kudzu that contain less than 1% or 2% isoavones are not effective in limiting alcohol intake, but a concentrated (25% isoavone) form of kudzu was effective in reducing alcohol intake by binge drinkers.30 The rate of alcoholism is high in cluster headache patients,31 which is surprising as alcohol is a reliable trigger of a cluster attack during a cluster period, although it may be consumed without consequence during a remission period. In one sample, 91% of cluster headache patients drank alcohol, with 61% falling into the category of moderate to excessive drinkers,32 and in another, more than 90% drank alcohol, with a signicant proportion being heavy drinkers.31 Levi found that 67% of his sample assessed with the Mm-MAST (Michigan Alcoholism Screening Test) had scores indicative of alcoholism.33 Other studies have found lower rates of alcohol consumption, but still far higher than those of noncluster headache controls 61% vs 41% in one sample,34 with daily use reported by 36% of cluster headache patients vs 14% of controls. However, as alcohol triggers cluster attacks, 79% of cluster headache patients dramatically decrease their alcohol consumption during a cluster period,33 in contrast with smoking, the rate of which does not change. It is thus conceivable that the isoavones in kudzu are treating a common factor underlying both alcoholism and cluster attacks. The use of kudzu to treat cluster headache was unknown before December 2005, when reports of its therapeutic effects appeared on the Internet and propagated rapidly through the cluster headache patient population. A number of studies have found that approximately 50% of patients use the Internet to obtain medical information, and 60% in one study reported that they felt that information on the Internet was the same as or better than information from their doctors.35 Although Internet medical advice is frequently characterized as inaccurate, incomplete, or inconsistent,36 the rapid and widespread dissemination of unveried medical information also permits the trial-and-error discovery of new treatments by enthusiastic patient groups.

103 Caution should be applied in interpreting these ndings, as case series are by their very nature subject to selection bias, recall bias, and the placebo response. However, several factors mitigate these limitations in this case series. Recruitment over the Internet selects for younger, more educated, and more motivated subjects,37 likely leading to increased reported efcacy. This group was not, however, otherwise selected for positive response to kudzu or alternative medications, and this group did not report a comparable positive response to acupuncture and other alternative medications. Although it has not been established that acupuncture and polydipsia are ineffective in treating cluster headache, if these methods are actually effective, then that would strengthen, not weaken, our conclusions. Although there was no placebo arm, cluster headache is known to respond poorly to placebo; controlled trials have shown a placebo response of 0% to prophylactic medications such as verapamil,38 capsaicin,39 and melatonin.40 As cluster attacks typically wax and wane over the course of a cluster period, improvement in symptoms can be difcult to attribute to medication effect. However, each cluster period is generally very similar in pattern and length for a given patient, making differences noticeable, and 2 patients (no. 4 and no. 12, see supplemental cases) used a challengerechallenge test to verify that the kudzu was having an effect on their headaches. Furthermore, 6 (38%) of the subjects had maintained detailed headache diaries corroborating their retrospective recall of efcacy. Finally, the concentration of isoavones in OTC kudzu preparations is unstandardized, and varies from 0.5% to 3% (Lukas, personal communication), making it difcult to quantify the actual amount of active ingredient ingested by the subjects. However, this variability should attenuate rather than exaggerate any doseresponse relationship, and the fact that such a relationship was still identiable despite the variable concentrations of isoavones present, further argues for therapeutic effect.

CONCLUSION Although few subjects were able to completely discontinue conventional medications, a substantial

104 proportion found that kudzu extract in a variety of low-concentration OTC preparations ameliorated the intensity, frequency, and duration of their cluster attacks, with minimal side effects, although kudzu had no effect on the length of the cluster period. Should these results be conrmed with a randomized clinical trial of standardized extracts, kudzu may prove to have a role in the management of cluster headache.
Acknowledgments: The author thanks Earth and Fire Erowid, Robert Wold and the Clusterbusters, for assistance with data collection; Harrison Pope, Scott Lukas, Mehmet Sofuoglu, and Bruce Price for their comments on an earlier draft of this article, and Jonathan Byron for bringing kudzu to the attention of the cluster headache community. Funding was provided by NIDA, NIH T32-DA07252. No funding source had any role in study design, collection, analysis, or interpretation of data, writing of the report, or submission of the manuscript.

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SUPPORTING INFORMATION
Additional Supporting Information may be found in the online version of this article: SUPPLEMENTAL CASE REPORTS FOR Response of Cluster Headache to Kudzu (Case no. 1, 4-16). Please note: Blackwell Publishing is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.

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Headache ! 2008 the Author Journal compilation ! 2008 American Headache Society

ISSN 0017-8748 doi: 10.111/j.1526-4610.2008.01268.x Published by Wiley Periodicals, Inc.

SUPPLEMENTAL CASE REPORTS FOR

Response of Cluster Headache to Kudzu


(Case no. 1, 4-16)

CASE #1 A 60-year old woman with no other medical conditions was diagnosed with episodic chronic cluster headaches at age 42 that became chronic at age 43. She usually suffered three but could have as many as eight attacks per day lasting 90 minutes each, following no pattern that she could discern. The attacks consisted of lacrimation, miosis, ptosis, rhinorrhea, injected sclera, flushing, diaphoresis, restlessness, and a boring pain in her temple. Her social life and marriage deteriorated as a result, and she became chronically depressed. Propanolol, verapamil, lithium, and amitriptyline had no effect on the frequency or intensity of her attacks, but she found oxygen and sumatriptan to be effective abortives. In February of 2005, she read on an Internet cluster-headache forum that kudzu extract could control cluster headache, so she started taking Natures Way 613 mg capsules three times a day. After two months, she noted no difference in the frequency or intensity of her attacksalbeit no side effects, eitherso discontinued the kudzu. She drinks a glass of red wine two or three times a week, smokes half a pack of cigarettes a day, drinks 3 or 4 cups of coffee a day, but uses no other drugs. CASE #4 A 47-year old woman with hypertension, asthma, and a history of ruptured MCA aneurysm had her first cluster attack in October 1973 at age 16 but was not diagnosed until May 2000, when she transformed to secondary chronic following years of misdiagnosis with migraine, sinus infection, and temporomandibular joint syndrome. Attacks were left-sided, could last for as long as an hour, occurred two to six times a day, and consisted of injected sclera, ptosis, lacrimation, rhinorrhea, pressure from nose to temple, neck spasms, and a feeling of having a hot poker driven into her eyeball combined with an

urge to bang her head into a wall. These attacks made it difficult for her to care for her newborn and were a contributing factor in two divorces. Propanolol, lithium, and verapamil were partially effective in treating her CH, although she found the lithium hard to tolerate, and oxygen was effective as an abortive only 50% of the time. She initially gained relief with rizatriptan but had to discontinue it because of concerns following her cerebral hemorrhage. In February of 2005, while taking 360 mg verapamil, 1800 mg gabapentin and 150 mg lithium carbonate daily, and still suffering attacks three times a day at 10 am, 2 pm and 10:30 pm, she read on an Internet site that kudzu had been used in Chinese medicine to treat migraines, so decided to selfadminister it. Starting with a 750 mg tablet of Planetary Formulas kudzu extract she noticed that within 24 hours her attacks ceased, and the residual pain that she had suffered for several hours a day was also cut in intensity and duration. Over several weeks she increased her dose to 4500 mg a day, and found that her attacks decreased in intensity and frequency to one every three or four days. She also began to experience phantom attacksautonomic attacks consisting of lacrimation, rhinorrhea, hidrosis, ptosis, eyelid edema, flushing, photo- and phonophobia, but no painroughly three times a day. She found the kudzu most effective when taken two hours prior to an expected attack. She was able to taper and discontinue both the lithium and gabapentin, but remained on verapamil at a reduced dose of 240 mg daily for her hypertension. In May she experienced six pain-free days in a row, and assuming that she had cured her disease, began to taper the kudzu by 750 mg daily to 1500 mg daily. Within four days, her daily attacks resumed, but were different in nature, lasting only ten minutes each and lacking the usual autonomic symptoms. She returned to her prior dose

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of 4500 mg kudzu, but never achieved the same level of relief again. The only side effect she noted was excessive flatulence. She rarely drinks, continues to smoke two packs a day of cigarettes and cannabis three times a month, but uses no other illicit drugs. CASE #5 A 38-year old woman with severe sinus headaches from her teen years had her first clearly identifiable six-week cluster period at age 28. At first her remission periods lasted for two years, but her cluster periods lengthened over time and she became secondarily chronic in July of 2003, and has experienced no more than seven pain-free days between attacks since. Attacks last between 25 minutes and three hours, average five a day, and consist of excruciating pain behind her right eye and temple radiating to the jaw, lacrimation, nasal congestion and rhinorrhea, conjunctival injection, forehead and facial sweating, miosis, flushing, phonophobia, tachycardia, anxiety, rocking, pacing, and inability to concentrate. They occur reliably at noon, 2 pm, 10 pm, 4:20 am and between 7 and 9 am, with additional attacks at 5 pm and 8 pm at peak, and have adversely affected her marriage, education, and social life. Propanolol and amitriptyline were ineffective, and verapamil caused unacceptable hypotension. Prednisone was effective but caused weight gain and extreme mood swings, and she became toxic on lithium before its efficacy could be determined. Sumatriptan was effective but caused her attack pattern to become irregular, and she had to discontinue it in May 2004 after she developed Prinzmetal angina. Oxygen initially worked miraculously but decreased in effectiveness as time went by and currently only works 50% of the time if used immediately at the beginning of an attack. She has tried over 50 medications in the last five years. In February 2005, while on a regimen of fentanyl 200 g twice daily and Tylox (acetamenophen/ oxycodone) 500/5 mg three times a day, she started taking kudzu as an adjunctive. After ten days of Natures Way 1226 mg in the morning she realized that her afternoon attacks had doubled in intensity. She stopped the kudzu but restarted it in the summer

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of 2005 without concurrent opiates, and again found that her afternoon attacks were much more painful. Taking kudzu before bed caused her to experience multiple nocturnal attacksmidnight, 2 am, and 4 amfor the first time. She discontinued it and continues to take fentanyl and Tylox with oxygen for breakthrough attacks. She smokes 1/2 pack a day, drinks rarely, and uses no other drugs except topical steroids for psoriasis. CASE #6 A 57-year old man with no other medical problems suffered episodic cluster headaches since age 20, each cluster period lasting from six to eight weeks, separated by a remission period of two years, although his most recent remission period was six years. Attacks occur up to four times a day, last one to two hours, and consist of lacrimation, ptosis, rhinorrhea, pacing, and chills. They cause him irritability but no serious problems in jobs or relationships. Neither methysergide, lithium, indomethacin, verapamil, prednisone, chlorpromazine, amitriptyline, melatonin, topiramate, nor naratriptan have had any effect on the frequency or intensity of his attacks. Sumatriptan was effective as an acute abortive, but he was forced to discontinue use after a myocardial infarction in 1998. Oxygen has been only partially effective, but he has not used a non-rebreather mask. A month following the end of his last cluster period in February 2005, and still experiencing heavy shadows every other day, he read that kudzu was reputed to treat cluster headache, so he took one dose of Planetary Formulas Kudzu Recovery 1500 mg at night. He noticed immediate jabs and joltsa phenomenon he had never experienced beforefor the rest of the evening but no shadows the following day. The kudzu gave him an upset stomach. The next day he began to experience shadows again, at which point he ingested Hawaiian baby woodrose seeds. The pain then stopped and did not return. He drinks a glass of wine on the weekend but does not smoke, use caffeine or illicit drugs. He remains on atenolol, pravastatin, and aspirin.

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CASE #7 A 57-year old woman without other medical conditions has suffered from two years of chronic cluster headaches consisting of an irregular pattern of nocturnal right-sided forty-minute cluster attacks that occur once a day within an hour and half of going to sleep, with no remission period longer than three weeks, with the exception of an interval on prednisone. These attacks consist of ptosis, nasal congestion, flushing, sweating, shivering, osmophobia, and severe pain in her right teeth and jaw. The pain has severely affected her social life, and interfered with her and her husbands sleep and peace of mind. Prednisone tapers have twice provided her with a pain-free period, and sumatriptan is partially effective in controlling her attacks. Reading that some people had found relief with kudzu, on February 24, 2005 she began taking Natures Way kudzu extract 1226 three times a day, and noticed that the attacks immediately shortened to five to ten minutes, occurred twice a week rather than every day, and became so much less intense that she no longer needed abortive medication. Her use of triptans declined from twice a week to none. On kudzu 1226 mg three times a day, a multivitamin, B-50 complex and B-12, she can now be pain-free for as long as two weeks between consecutive attacks. She notices no side effects from the kudzu, smokes one pack a day but does not drink or use illicit drugs. CASE #8 A 32-year old man without other medical conditions has suffered episodic cluster headache since age 26, consisting of eight-week cluster periods separated by four-month remission periods. During a cluster period, he will experience four to six 90minute mostly nocturnal cluster attacks that feel like an ice-cream headache only worse. The attacks start with a dull ache behind the right eye, slowly increase in intensity over five minutes to a constant boring pain that spreads to the upper teeth, and is associated with ptosis, conjunctival injection, tearing, photophobia, and a compulsion to press his right temple. These can be triggered by alcohol or odors of gasoline, diesel fumes, nail polish, and perfume.

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Until he was finally diagnosed in February 2005, he underwent two courses of antibiotics a year for presumed sinus infections, and had three healthy teeth removed. He had to stop working as a train conductor after he almost caused a derailment during a cluster attack. During a cluster period, he will get only two or three hours of sleep a night for weeks, causing him to be irritable and adversely affecting his relationship with his wife. Sleep deprivation also impaired his ability to study and forced him to drop out of college. As a prophylactic, prednisone was ineffective, and valproate doubled the frequency of his attacks, but verapamil 480 mg reduced both the intensity of the attacks by a third and the frequency by 20%. Sumatriptan is effective, and oxygen is completely effective 75% of the time and reduces the intensity of remaining attacks the remainder of the time. Melatonin causes the attacks to shift from diurnal to nocturnal. An extended cluster period began in February 2005 that lasted for nine months. In April he tried Planetary Formulas kudzu extract 1500 mg twice a day, increasing to three times a day after two months. After three months of co-administration with verapamil, melatonin, sumatriptan and oxygen, he noted no change in the frequency or intensity of his attacks, but suffered from gastrointestinal distress, so discontinued it. Subsequently, there was no noticeable difference in his cluster attacks, which were occurring three to five times a day. He took psilocybin mushrooms in October 2005 and the cluster period stopped. He has been pain-free since. He smokes a pack and a half and drinks up to two pots of coffee a day, but does not drink alcohol or use illicit drugs. CASE #9 A 49-year old man with no other medical conditions has endured episodic cluster headache since age 20, diagnosed at age 35. Every 10 to 13 months he will experience nine months of hour-long attacks that occur up to four times daily, consisting of intense non-throbbing pain centered in his right eye, associated with lacrimation, rhinorrhea, pacing, irritability, and rocking back and forth. These attacks

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have disrupted his social life, because he often cannot risk attending social events, and his professional life as a University administrator, because he lives in fear of a cluster attack removing his ability to successfully think through problems. Propanolol was ineffective in ameliorating his attacks, while verapamil was effective for about three years then ceased to work. Prednisone was effective but caused him unpleasant mood changes, excessive weight gain and edema, and topiramate caused him paresthesias and hallucinations. He can reliably abort acute attacks with sumatriptan and occasionally with oxygen. Frustrated with what he considered to be unacceptable side effects from the prophylactic agents he had tried, when his current cluster period began on May 29, 2005, he decided to take kudzu instead, which he had read about on an online cluster headache forum. On June 7, he started taking 1500 mg Planetary Formula kudzu three times a day, and noted a slight decrease in the intensity and duration of his attacks and an immediate decrease in their frequency from four a day to two or fewer. Skipping a dose of kudzu or even changing the timing of a dose results in an immediate increase in the frequency but not the intensity of the attacks. The only side effects he suffered were indigestion and a looser neck. He drinks alcohol once or twice a week when in a remission period, smokes cigarettes when he drinks, but uses no illegal drugs. He has one or two cups of coffee a day. He can continue to have one or two mild attacks a day on kudzu, ergotamine tartrate 2 mg at night, and melatonin 9 mg at night. CASE #10 A 49 year old right-handed man has had cluster headache since age 13, becoming secondarily chronic at age 25. He had been run over by a car at age 4, resulting in persistent cognitive deficits from his brain injury, and also suffers from migraines and depression. He can have up to 6 attacks a day that are mostly right-sided but that can alternate within the same cluster period, consisting of 30 minutes of lancinating pain, eyelid edema, and ptosis that cause him to scream, sob, and punch himself in the head and that have left him with a permanent right eyelid

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droop. Attacks occur night and day, making it difficult for him to keep a job, as he has frequently quit impulsively while in a cluster period. His mood is frequently so foul during his worst periods that his family has to walk around on eggshells. He found amitriptyline and methadone, which he started in his 30s, to be partially effective at controlling his attacks, but did not like the mental dullness or difficulties with orgasm that they gave him. Lithium was ineffective, and sumatriptan was effective in controlling his attacks, but becoming less so with time and eventually causing increased intensity attacks, anxiety, and confusion that stopped when he discontinued it. At this time he was forced to go on permanent disability. In April 2005 he read on the Internet about the kudzu treatment for cluster headache. He discontinued his methadone and alprazolam, but not his melatonin, suffering five days of withdrawal symptoms, then started kudzu extract (Planetary Formulas, Kudzu Recovery) 750 mg three times daily, noticing no effect. Upon increasing this to 1500 mg three times daily, he noticed an immediate 50% decrease in the intensity of his pain, although the frequency of the attacks remained unchanged. After two months on kudzu, he decided that although it was more effective for him than sumatriptan or morphine, the discontinuation of his other medications had caused his insomnia, restless leg syndrome, and chronic pain to worsen. He therefore discontinued the kudzu and instead took Hawaiian baby woodrose seeds for prophylaxis, finding them to be more effective than kudzu, and sumatriptan for breakthrough attacks. He remains on morphine SR 60 mg for chronic pain and alprazolam 1 mg. He does not smoke, drink, or use recreational drugs. CASE #11 A 43-year old right-handed woman in Louisiana with no other medical conditions except for gastroesophageal reflux disease has had episodic cluster headache since age 12. Each cluster period lasts six to eight weeks separated by a remission period of 7 to 18 months. At worst, she will suffer three two-hour attacks per day, mostly nocturnal, consisting of lacrimation, ptosis, conjunctival

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injection, rhinorrhea, diaphoresis, restlessness, neck stiffness, and severe, boring pain in her eye, ear, and temple. These have deprived her of sleep and made her irritable, embarrassed for repeated cancelling social plans, guilty over her inability to be industrious during a cluster period, and resigned to remaining in a bad marriage for fear that her condition will make it impossible for her to find another partner. She has found propanolol ineffective, and verapamil and prednisone partially effective in decreasing the frequency and severity of attacks. Oxygen lessens the intensity of attacks but does not truncate them; triptans abort an attack about a quarter of the time. In July 2005, her fianc read an article that said that kudzu could potentially help her cluster headache. When her most recent cluster period started that month, she started taking Natures Way 613 mg twice a day for the next three weeks, but found that her attacks were worsemore intense, more frequent during daylight hours, and longer, and the cluster period itself was also longer than normal. This coincided with hurricane Katrinas landfall, however, and with it a month of increased stress, 95degree temperatures, and no electricity or air conditioning. She stopped taking the kudzu when it ran out. She experienced no side effects from the kudzu. She currently smokes one pack per day of cigarettes, drinks one or two servings of alcohol several times a week and three to five cups of coffee a day, but uses no illegal drugs. CASE #12 A 42-year old man without any other medical problems has had episodic cluster headaches since his late twenties. For four to six weeks, twice a year, he suffers one or two right-sided cluster attacks daily or every other day, lasting one to three hours each. These are characterized by rhinorrhea, ptosis, mydriasis, and severe orbital pain that often leaves him unable to do anything but rock back and forth or writhe around on the floor. During these periods, he is forced to schedule his personal and professional life around anticipated attacks, which is disruptive and anxiety-provoking for him and his family.

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He had used no medication prior to his most recent cluster period, which began in February 2005, after which he used both oxygen and intramuscular sumatriptan and found them effective in terminating his cluster attacks in less than 15 minutes. Finding a reference online to kudzu in February 2005, he started taking 1226 mg Natures Way kudzu extract three times a day and found that the frequency and intensity of his attacks dropped almost to zero. He had only two more attacks during that cluster period. In July 2005, he started to suffer cluster attacks that were provoked by vigorous exercise, heralding the beginning of another cluster period, so he restarted kudzu at the same dose. He experienced only five or six half-strength attacks for the remainder of the cluster periodfour weeksand these attacks did not occur spontaneously, but rather were triggered by aerobic exercise or alcohol, and responded promptly to oxygen. This scenario repeated almost exactly during his next cluster period, which began in January of 2006. Despite the infrequency of attacks, he is able to tell that he remains in the cluster period by a subtle heaviness in his head and tickle behind his eyeball, and in a remission period he is able to consume alcohol and run a marathon once or twice a year without triggering an attack. He notices no side effects from the kudzu. When his most recent cluster period started on March 12th, 2006, he began taking Planetary Formulas 1500 mg twice a day and found it less effective than Natures Way but better than nothingalthough his cluster attacks were only 10 to 15 minutes in length and aborted by oxygen, and much less painful in intensity, he continued to have an attack almost every day. Discontinuing kudzu increased the frequency to two or three a night. His father is his only relative known to have cluster headache. Neither he nor his father has a history of head injury, although his fathers brother had a seizure disorder. He drinks one or two beers or glasses of wine a day, stopped smoking nine years ago, and uses no illicit drugs.

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CASE #13 A 40-year-old woman with osteomalacia and collagenous colitis has had chronic cluster headache since age 38, when she tapered off the prednisone that she had been taking for her celiac disease over nine months. If unmedicated, she will have between three and eight cluster attacks a day, lasting two hours each, and consisting of a boring pain in her temple accompanied by an urge to gouge out her eye, lacrimation, ptosis, miosis, rhinorrhea, and sweating. She was forced to stop working, and her marriage ended. Verapamil caused syncope, lithium was ineffective, and topiramate caused hallucinations and delusions, but oxygen will reliably end an attack in five minutes. Triptans are also effective but sumatriptan caused tachycardia, nausea, and dysphoria, and frovatriptan caused the intensity of her attacks to increase. In December 2005, having read on the Internet that kudzu was effective in treating cluster headache, she started taking Natures Way 1226 mg three times a day and noted that the intensity of her attacks decreased by 50% and the frequency dropped to two to three attacks per day. After 13 weeks, the frequency slowly increased back to baseline, so she stopped kudzu and switched to verapamil, then topiramate, then lithium, hoping that they might be more effective, which turned out not to be the case. She suffered no side effects from the kudzu. She does not smoke or use illegal drugs, drinks alcohol twice a week, and drinks three coffees or sodas a day. She currently takes only Rivea corymbosa seeds and oxygen to treat her cluster headache. CASE #14 A 31-year old woman without other medical conditions suffered from episodic cluster headaches since age 16 that occurred for five week periods separated by 11 month to 3-year remission periods. At peak, she can have four 50-minute attacks per day, consisting of severe boring pain, rhinorrhea, ptosis, rocking, moaning, and compulsively rubbing or hitting her temple. This leads to sleep-deprivation and irritability, adversely affecting her relationship

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with her husband. She was initially treated for sinus infections every September during her regular cluster period, until she finally received the correct diagnosis in 2000. Amitriptyline had no effect on the frequency or intensity of her attacks, and prednisone rendered her pain-free for only two days. Oxygen worked for half of her cluster period in 2000, but not subsequent to that. Injectable sumatriptan works 95% of the time. In 2004, she read on an Internet forum that kudzu extract could be used to treat cluster headache, so at the anticipated beginning of her next cluster period in September 2005, she began to take Neutraceuticals Sciences Institute kudzu extract 650 mg daily. During that month, her cluster period did not begin in its usual fashion; rather, she experienced three phantom attacks, consisting of unilateral nasal congestion, ptosis, and flushing but without any pain. These were otherwise identical to her regular attacks except that they lasted for only two or three minutes. In mid-October she discontinued the kudzu, but when her cluster period began late in December, she restarted kudzu at 650 mg one to three times a day and for the remainder of the six weeks of her cluster period noted that both the intensity and frequency of subsequent attacks were lessened. By themselves, the attacks were not shorter, but oxygen, which had ceased to work, became effective again as an abortive in combination with the kudzu. Her cluster period remained the same length. She experienced no side effects other than loose bowels. She remained on duloxetine, alprazolam, and vitamins during this period. She stopped smoking a pack a day a year ago, and drinks two to four glasses of red wine four times a week, but uses no illicit drugs or caffeine. CASE #15 A 49-year old man with no medical history other than a concussion from a motorcycle accident at age 16 started to have episodic cluster headache at age 23, consisting of two-month cluster periods every 18 to 24 months that often started during times of relaxation following stressful periods such as a deadline. At worst he will get two left-sided attacks a day, lasting up to three hours each, characterized by a

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boring pain in his temple with waves of more severe pain approximately every ten minutes, a hot knot in his neck and throat, miosis, lacrimation, conjunctival injection, rhinorrhea, flushing, diaphoresis, restlessness, photophobia, and a feeling like an alien in my head wants out. During the attacks he is completely incapacitated, and by the second week of a cluster period, sleep deprivation renders him irritable and unable to focus or make decisions at home or at work. His neurologist has recommended that he eliminate foods such as cheese, nuts, chocolate, coconut, shellfish, tomatoes, alcohol and just about anything "aged" from his diet, which causes inconvenience when eating out or at social gatherings. He also lost one five-year romantic relationship in part because of his cluster headache. Acupuncture has not helped his cluster headache, nor has prednisone, which instead gave him anxiety, depression, irritability, and mood swings. Oxygen and rizatriptan, which he combines with a few drops of Bach Flower Rescue Remedy and a cup of hot coffee, are effective in aborting individual attacks. He has also taken Cafergot, codeine, Vicodin, Dilaudid, melatonin, Chinese herbal medicine and feverfew, and tried homeopathy, craniosacral therapy, and Quantum Energetics therapy. The Cafergot worked only occasionally, and only if taken immediately at the onset of a headache. Dilaudid helps early in the cluster period, but increasing doses are required as the cluster period continues. In November 2005, one week into his most recent cluster period, he read about kudzu on an Internet forum, so started taking StarWest Botanicals Inc. bulk kudzu root 800 mg to 1000 mg at night, combined with drinking four to five liters of spring water during the course of the day. He noted no change in the intensity, frequency, or duration of attacks, but his cluster period ended after only three weeks. He experienced no side effects from the kudzu. He does not smoke, and while in a cluster period does not drink alcohol or use illegal drugs, but will drink coffee to help abort individual attacks. In a remission period, he smokes prescribed medical cannabis once or twice a day but uses no illegal

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drugs, drinks 2.5 glasses of red wine daily, and drinks a cup of coffee every morning. CASE #16 A 33-year old right-handed woman with no other medical conditions was diagnosed with episodic cluster headache at age 22, consisting of progressively longercurrently eight weekcluster periods separated by nine- to twelve-month remission periods. She experiences one or two 60-minute attacks a day, characterized by ptosis, diaphoresis, restlessness, photo- and osmophobia, and pain that she describes as like a lightning storm or worms dipped in acid crawling through the right side of my head. She has suffered lost productivity in her job from lingering headaches and medication side effects, and since her triggers during a cluster period include flickering lights and chemical smells, she cannot go to bars, restaurants, grocery stores or movies, severely impacting her social life. Amitriptyline is ineffective as a prophylactic agent, verapamil and duloxetine are partially effective, and prednisone prevents attacks while she takes it. Intranasal sumatriptan effectively aborts her attacks. In fall of 2005 she read on the Internet that kudzu might be effective in treating cluster headache, so she started taking Natures Herb 100 mg daily, but noted no decrease in the frequency, intensity, or duration of her cluster attacks and no effect on the length of her cluster period. She suffered no side effects from the kudzu, however. She currently maintains herself on a combination of duloxetine, verapamil, kudzu, magnesium, and melatonin. She does not smoke or use illegal drugs, but drinks occasional alcohol when in a remission period.