Antimigraine herbs

Treatment of vascular headache involves not only relief of the intense pain of an acute attack but also the prevention (prophylaxis) of additional attacks. During the past decade, research has demonstrated the prophylactic value in the following herbs in treating migraine.

Feverfew Valued since the time of Dioscorides (a.d. 78) as a febrifuge (antipyretic), the leaves of Tanacetum parthenium (L.) Schultz Bip. syn. Chrysanthemum parthenium (L.) Bernh. have now been shown to be useful in reducing the frequency and severity of migraine as well as the discomfort of the fre- quently associated nausea and vomiting. A daily dose of 50–250 mg of dried leaf is recommended for prophylaxis. 105

Seven randomized double-blind, placebo-controlled clinical trials (RCTs) have been conducted with feverfew monopreparations; five were reported to be successful, three employing dried powdered fever-

few leaf. 106–108 Two recent German studies used the same proprietary CO 2 supercritical fluid extract (SFE). 109,110 The first six of these trials have been systematically reviewed. 111 Of the two failed trials, one cannot be properly evaluated because it is available only as an abstract of a poster presenta- tion, with no information as to the particular character of the feverfew preparation or details about outcome measures. 112 The other trial, conducted in the Netherlands, involved a 90 percent alcohol extract of feverfew leaf amply charged (>4 percent) with the then-putative antimigraine principle of feverfew, parthenolide, 113 the germacranolide sesquiterpene

lactone, then thought to exert its influence by engaging in Michael addition with free sulfhydryl groups in platelets, thereby inhibiting release of sero- tonin. 114 The imposition by the Canadian regulatory authority of the crite- rion of a minimum of 0.2 percent parthenolide for acceptance of the claim as a migraine prophylactic was meant simply to ensure identity with the clinically proven sesquiterpene lactone chemotype of feverfew. The failed Dutch trial, contrasted with the later successful Israeli trial 108 with feverfew

leaf containing 0.2 percent parthenolide, obviously discredits parthenolide as an appreciable contributor to feverfew’s antimigraine activity.

138 Tyler's herbs of choice: The therapeutic use of phytomedicinals The failure of the Dutch trial with an ethanolic extract of feverfew

was likely due to loss of the true, yet unidentified, active principle(s), probably due to degradation during the protracted preparation and pro- cessing. The leaf material was macerated at ambient temperature for twelve days with occasional stirring, filtered, and then digested for seven more days! It should also be noted that the two recent trials 109,110 with

a feverfew leaf CO 2 -SFE product (MIG-99, Schaper & Brümmer GmbH, Salzgitter, Germany) demonstrated primary efficacy in only a small sub- set of patients who had experienced at least four migraine attacks during the four-week baseline period preceding the trials. The scientific com- munity awaits the clinical trial of an undegraded hydroalcoholic extract of feverfew for migraine prevention.

No serious adverse effects have been associated with consumption of feverfew. In a survey of roughly 270 people who had been using feverfew for two to four years (more than 70 percent of whom claimed less fre- quent or less painful headaches, or both) conducted by the City of London Migraine Clinic, 18 percent reported adverse events. The most trouble- some was the formation in the mouth of recurrent, so-called aphthous, ulcers experienced by 11.3 percent and severe enough in 7 percent as to prompt discontinuation of therapy; 6.5 percent of respondents reported experiencing indigestion. About 40 percent of users, however, attributed pleasant side effects to feverfew, noting, among other experiences: a sense of well-being, relief of the symptoms of coexisting arthritis, and tranquil- izing effects such as more restful sleep and reduced muscular tension. 115

Aphtous ulceration is apparently a systemic effect that resolves within a week or so of discontinuation of the treatment but returns on rechallenge. 116 Interestingly, the clinical trial conducted at the University

of Nottingham 107 reported that more patients in the placebo group (n = 16) reported mouth ulceration than in the verum group (n = 10). Also inter- esting is the observation that the nonsteroidal anti-inflammatory drugs (NSAIDs) increasingly used for migraine prophylaxis and arthritis also cause recurrent aphthous ulceration; the effect occurs particularly with drugs that produce substantial inhibition of the cyclooxygenase path- way. 117 It has been claimed that this mouth ulceration can be alleviated

by treatment with tincture of myrrh (Commiphora sp.). 118 The bitter-tasting feverfew leaves sometimes induce a more generalized inflammation of the oral mucosa and tongue, with attendant swelling of the lips and loss of taste. The soreness is likely caused by direct contact with leaves during chewing and is probably due to interaction with sesquiterpene lactones known to cause contact dermatitis. 119

A “postfeverfew syndrome” has been identified in about 10 percent of long-term feverfew users who stopped taking the herb; about one-tenth experienced moderate to severe aches, pains, and stiffness in joints and muscles, along with CNS symptoms of anxiety and poor sleep. 106 It has

Chapter seven: Nervous system disorders 139 been speculated that such sleep disturbances may be due to withdrawal of

melatonin, present in appreciable quantities in the leaf (2.45 µ/g in fresh;

2.19 µ/g in dried). 67 In view of feverfew’s traditional reputation as an emmenagogue to induce uterine contraction in full-term women and its ability to cause abor- tion in cattle, it would seem prudent to forego its use during pregnancy or lactation. It should be noted, however, that when feverfew has been used to promote menstruation, it was taken in much higher doses than cur- rently employed for treating migraine and arthritis. Finally, little is known of the effects of feverfew on migraine and arthritis in pregnancy. 116 There

are no reports of feverfew causing teratogenic side effects and no data on its safety during lactation. A study involving thirty females who had been consuming feverfew for more than eleven months revealed no differences in the frequency of chromosomal aberrations or the frequency of sister chromatid exchanges compared with a matched set of nonusers. 120

Feverfew is also contraindicated in persons with recognized hyper- sensitivity to other members of the Asteraceae (Compositae) because cross-reactivity is common among plants in this family. 121 No substantial information on feverfew use by children is available.

Butterbur Extracts of both leaves and root/rhizome of Petasites hybridus (L.) Gaertn, Meyer & Scherb. (Asteraceae/Compositae) have been clinically tested as migraine prophylactic as well as treatment for seasonal allergic rhini- tis. The Swiss company Zeller AG manufactures an extract of butterbur leaves (Ze339), standardized to contain 25–35 percent petasins (sesquiterpene esters). Marketed as Tesalin™, a root extract, Petadolex™ is pro- duced by Weber and Weber in Petaforce™ and is available from Bioforce Ltd., Irvine, United Kingdom. These manufacturers claim that the hepa- totoxic and potentially carcinogenic pyrrolizidine alkaloids (PAs) of butterbur have been removed. 122 However, preparations from the rhizome of P. hybridus were removed from the market in Switzerland in early 2004. 123

Nonetheless, Petadolex was submitted to clinical trials for prophylaxis of migraine. 124–126 Both migraine studies noted a significant reduction in frequency of migraine attacks, as well as excellent tolerability, recom- mending butterbur as a effective migraine prophylactic.

A report published in 2003 assessed the safety of Petadolex. 127 Results from acute, subchronic, and chronic animal toxicity studies, as well as safety data from clinical trials, post-marketing surveillance studies, and pharmacovigilance, were evaluated and discussed. The patented butterbur root extract was judged safe for treatment in humans. Thus far, only four cases of a reversible cholestatic hepatitis have been probably associated with long-term administration of butterbur (incidence of 1:175,000). 128

140 Tyler's herbs of choice: The therapeutic use of phytomedicinals Ginger

One case history from Denmark in 1990 reported the beneficial effect of ginger in aborting the effects of migraine headache: a forty-two-year-old female migraineur given 1.5–2.0 g of powdered ginger daily at the onset of a migraine attack experienced marked reduction in the frequency and severity of migraine headache. 129 Recently, a proprietary product (Gelstat Migraine) has been claimed effective as a sublingually administered feverfew and ginger compound for treatment of acute migraine during the mild pain phase. 130

Cannabis Cannabis sativa L., Cannabaceae, was once a widely accepted medi- cal treatment for the prevention and relief of migraine headache, listed in the United States Pharmacopeia from 1860 to 1941. 131 Savitex ® (GW

Pharmaceuticals, Salisbury, UK) is a cannabis-based blend of whole plant extracts that delivers approximately equal amounts of ∆-9-tetrahydrocan- nabinol (THC) and cannabidiol (CBD). THC has analgesic activity in both nociceptive and neuropathic pain, and both THC and CBD exert anti- inflammatory effects. Savitex has been approved for several medicinal applications in the United Kingdom and is also available by prescription in Canada for symptomatic relief of neuropathic pain in multiple sclerosis (MS). Clinical trials conducted in the United Kingdom support the benefit of the cannabis-based medicine in MS 132 and rheumatoid arthritis. 133

Antimigraine herbs