Migraine (2) - 1

MIGRAINE
REPORT
SUBMITTED TO
ABHILASHI COLLEGE OF PHARMACY

FOR AWARD THE DEGREE OF B. PHARMACY
SUPERVISED BY: SUBMITTED BY:

Nancy Sharma Karan Sharma (1921141043)
Bhuvneshwar (1921141026)
Assistant professor
AABHILASHI COLLEGE
OF PHARMACY NERCHOWK, MANDI H.P 175008
1. INTRODUCTION
Vinayaka College Of Pharmacy

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Migraine was derived from the Latin word “hemicrania” meaning “half” (hemi) “skull” (crania). This
term was first used by Galenus of Pergamon to describe the pain felt across one side of the head
during a migraine.The term classical migraine has been replaced with migraine with aura.
Nonclassical term for migraine now is referred to as migraine without aura. [1]
Most common type is “Migraine without aura”.Pain will be one side (or) both side of head with
symptoms mood swing, nausea, photophobia, vomiting and fatigue.
Second type’s is “migraine with aura”. In these type of migraine symptoms appears before 10-30
min of Attack.[2]
There are several types of headaches, each with its own set of symptoms,causes ,pain . These types
include tension, cluster, migraine, sensitivity, sinus, trauma, and eyestrain headaches [3]
Migraine is a common chronic headache disorder, recurrent attacks lasting 4–72 hours, of a pulsating
quality, moderate or severe intensity aggravated by routine physical activity and associated with
nausea, vomiting, photophobia or phonophobia. [4]
Headache is considered a main health problem due to high prevalence and associated disabilities of
different types of headaches, migraine, with 6% and 18% prevalence in men and women respectively,
is considered the third leading disorder and the seventh leading cause of disability . Migraine headache
occurs as periodical attacks and may be manifested by nausea, vomiting, photophobia, and

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phonophobia . Migraine is a main reason for absence from work and therefore imposes heavy burden
on individuals and communities because of disabling workforce Clinical heterogeneity of migraine
arises from different genetic and environmental factors and lifestyle .
Therefore, many treatments have been adopted, including chemical drugs, psychotherapy,
antiepileptics,antidepressants, acupuncture, and traditional medicine. However, some of these could
not be used for all patients and have not been approved by specialists . Furthermore, side effects are
the main problem of certain pharmacotherapies [5]
Medicinal plants play an important role in the human health care. Majority of the world population
relies on the use of traditional medicine, which is predominantly based on plant material. The
traditional medicine refers to a broad range of ancient natural healthcare practices like Ayurveda,
Siddha and Unani.
These medical practices originated from times immemorial and developed gradually, to a large extent,
by relying or being based on practical experiences without significant references to modern scientific
principles. [6]
Migraine is a familiar disorder characterized by recurrent attacks of pulsatile headache. It is a disorder
with number of manifestations that involves the brain, eyes and the autonomous nervous system.
It is reoccurring syndrome of headache associated with another neurological dysfunction. Migraine
headaches result from a combination of blood vessel enlargement and the release of chemicals from
nerve fibers that coil around these blood vessels.
When headache accur, any artery enlarges and which is located on the outside of the skull just under
the skin of the temple (temporal artery).
This causes a release of chemicals that cause inflammation pain, and further enlargement of the artery.
It is, however, believed to be a neurovascular disorder [7]
Over 45 million Americans suffer from chronic headaches; of these, 16 to 18 million suffer from
migraines annually. It is estimated that industry loses 50 billion dollars per year due to absenteeism
and medical expenses caused by headache, and migraine sufferers lose more than 157 million
workdays each year. In excess of 4 billion dollars are spent annually on overthe-counter pain relievers
for headache, many of which prove ineffective.
Although the theories regarding the underlying causes of migraine vary considerably, it is widely
believed that all migraines ultimately relate to abnormal platelet behavior. During a migraine attack,
platelets have a tendency to over-aggregate and release serotonin, causing abnormal constriction and
dilation of the blood vessels in the head, which stimulates nearby nerve endings and causes headache.

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[8]
Symptoms The knowledge of symptom is very essential for diagnosis, prognosis and proper
management of the disease. The symptoms of Ardhavabhedaka mentioned in classics can be classified
as:
• Site of pain,
• Nature of pain,
• Time specified for the attack of pain,
• Symptoms Site of the pain:
• Ardhashira- half part of the head,
• Manya- either side of neck.
Therefore, gathering data of medicinal plants and the methods of using these in different regions is a
valuable resource about old medicine at present time. This helps to discover new drugs and to
advance pharmaceutical industry, as well [9].
Diagnosing Migraine:
Evolving diagnostic criteria have facilitated the diagnosis and study of headache in general and
migraine in particular. Migraine is the most common severe primary headache. It has six subtypes,
several of which have subforms (Table 1)
The forms of migraine most frequently experienced are migraine without aura, typical aura with
migraine headache, and typical aura without headache. In one population study, 64% of patients with
migraine had migraine without aura, 18% had migraine with aura, 13% had both types of migraine,
and 5% could not be subtyped. The International Classification of Headache Disorders, Second
Edition (ICHD-II) diagnostic criteria for common forms of migraine and typical aura are provided in
Table 2.[10]

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Table 1
Subtypes and Subforms of Migraine
Migraine without aura Migraine with aura

• Typical aura with migraine headache
• Typical aura with nonmigraine headache
• Typical aura without headache
• Familial hemiplegic migraine
• Sporadic hemiplegic migraine
• Basilar-type migraine
Childhood periodic syndromes that

are commonly precursors of migraine
• Cyclical vomiting
• Abdominal migraine
• Benign paroxysmal vertigo of childhood
Retinal migraine Complications of migraine

• Chronic migraine
• Status migrainosus
• Persistent aura without infarction
• Migrainous infarction
• Migraine-triggered seizure
Probable migraine
• Probable migraine without aura
• Probable migraine with aura
• Probable chronic migraine
Source: Headache Classification Subcommittee of the International Headache Society. The International
Classification of Headache Disorders: 2nd edition. Available at: www.ihs-classification.org/en/. Accessed April
15, 2010.

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Table 2
Criteria for Diagnosing Migraine
Migraine without aura

A. At least five attacks fulfilling criteria B-D
B. Headache attacks lasting four to 72 hours (untreated or unsuccessfully treated)
C. Headache has at least two of the following characteristics:
1. Unilateral location
2. Pulsating quality
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (eg, walking
or climbing stairs)
D. During headache at least one of the following:
1. Nausea and/or vomiting
2. Photophobia and phonophobia
E. Not attributed to another disorder
Typical aura with migraine headache

A. At least two attacks fulfilling criteria B-D
B. Aura consisting of at least one of the following, but no motor weakness:
1. Fully reversible visual symptoms including positive features (eg, flickering
lights, spots, or lines) and/or negative features (ie, loss of vision)
2. Fully reversible sensory symptoms including positive features (ie, pins and
needles) and/or negative features (ie, numbness)
3. Fully reversible dysphasic speech disturbance
C. At least two of the following:
1. Homonymous visual symptoms and/or unilateral sensory symptoms
2. At least one aura symptom developing gradually over ≥5 minutes and/or
different aura symptoms occurring in succession over ≥5 minutes
3. Each symptom lasting ≥5 and ≤60 minutes

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D. Headache fulfilling criteria B-D for migraine without aura begins during the aura
or within 60 minutes
E. Not attributed to another disorder
Typical aura without headache is the same as typical aura with migraine headache,
except that criterion D is replaced by “Headache does not occur during aura nor follow
aura within 60 minutes.”
Source: Headache Classification Subcommittee of the International Headache Society. The International
Classification of Headache Disorders: 2nd edition. Available at: www.ihs-classification.org/en/.
Accessed April 15, 2010.
1.2 PATHOPHYSIOLOGY
1. Vascular and Neurogenic theories
The cause of migraine headache is still not completely understood. Historically, two independent
theories, the vascular theory and the neuronal theory, explaining the etiology of migraine headache
were proposed. The vascular theory was introduced by Thomas Willis where he recognized that “all
pain is an action violated” and argued the pain from headache is caused by vasodilatation of the
cerebral and meningeal arteries. The alternative neurogenic theory focuses on the cause of migraine
pain and is currently linked to activation of the trigeminovascular system.
2. Cortical Spreading Depression

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The alternative and widely accepted theory suggests that cortical spreading depression (CSD), a wave
a neuronal hyperactivity followed by an area of cortical depression, accounts for the aura and that the
headache depends on activation of the trigeminovascular pain pathway. In Chronic Migraine (CM),
atypical pain processing, central and peripheral sensitization, cortical hyper excitability, and
neurogenic inflammation all have a role to play. Cortical hyper excitability is thought to be another
major factor participating in transformation of EM to CM.[4]
3. CORTICAL HYPEREXCITABILITY IN MIGRAIN

As is the case for many episodic disorders, the trigger for migraine attacks has not been precisely
identified. Many clinical factors such as diet, alterations in sleep and stress are known to predispose
individuals to attacks. It is particularly intriguing that photic stimulation can trigger both migraine
attacks and epileptic seizures. How these factors bring on a migraine attack is not known. However,
there is evidence for enhanced cortical responsiveness to diverse stimuli in migraineurs. The
techniques that have been used to generate this evidence include psychophysical studies; visual,
auditory, and somato sensory evoked potentials; magneto encephalography; and transcranial magnetic
stimulation of the motor cortex. In all cases, there is evidence of heightened reactivity between
migraine attacks. Results from transcranial magnetic stimulation of the occipital (visual) cortex have
been particularly compelling. Most but not all studies have observed that migraineurs have a reduced
threshold for induction of phosphenes (the experience of light with non luminous stimulation)
compared with controls. This phenomenon appears to be equally present in individuals who
experience migraines with and without aura. Thus, a pathologically low threshold for activation of
cortical hyper excitability may characterize migraine [11]
1.3 TRIGGER FOR MIGRAINE
Mollaoglu M, 2012 conducted study which shows that the most common trigger factors were
emotional stress (79%), sleep disturbance (64%) and dietary factors (44%).
Sleep and stress were significant trigger factors in patients with migraine with aura, whereas
environmental factors were important trigger factors in patients with migraine without aura.
environmental factor stress, genetic factors ,sleep are important trigger factors in women. Trigger
factors are frequent in migraine patients, and avoid such factors may result in a better control of the
disorder. [12]

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Migraine causing is not understood but it is due to some trigger that causes inflammation of blood vessels in
head. There by it leads to vascular constriction or dilation (or) inflammation of blood vessel and causes pain in
head. [2]
1.3 CLINICAL FEATURE:
Headache is considered a main health problem due to high prevalence and associated disabilities
. Of different types of headaches, migraine, with 6% and 18% prevalence in men and women
[13,14,]
respectively, is considered the third leading disorder and the seventh leading cause of disability [15,16]
A great deal of interest has focused on the activity of feverfew in the treatment and prevention of
migraine headaches. [17] The first modern, public account of its use as a preventative for migraine
appeared in 1978. The story, reported in the British Health Magazine, Prevention, concerned a
patient who suffered from severe migraine for 16 years of age. At 68 years of age, she began using 3
leaves of feverfew daily, and after 10 months her headache ceased completely.
1.4 ETIOLOGY:
 Environmental triggers like Loud noises, bright lights, certain odours and perfumes
 Allergic reactions and allergies
 Psychological triggers like emotional stress
 Irregular sleep or changes in sleep pattern
 Alcohol consumption
 Physical triggers like birth control pills, menstrual cycle fluctuations,
 Food additives like monosodium glutamate (MSG), aspartame, phenylethylamine, nitrates, and
tyramine. Also, chocolates, citrus fruits, nuts,
peanut butter, meat that has been cured or processed, large amount of aspartame are some other
examples for food triggers.[18]

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1.5 HISTORY
History has troubled mankind from the dawn of civilization. The earliest symptoms in migraine were
those of supernatural and migraine was believed to be due to malevolent beings within the head;
treatment based on this idea included incantations and application to the head of substances intended
to drive out the demons and spirits.
Around 400 BC, the ancient Greek physician, Hippocrates, released migraine from the realms of the
supernatural by attributing it to vapors rising from the stomach to the head and described, for the first
time, the visual symptoms (“aura”) of migraine. Galen wrote of “a painful disorder affecting
approximately one-half of the head” his term for this, “hemicrania," was gradually transmuted into
“migraine."
The Hippocratic/galenic concept of migraine survived into the 17thcentury, when Thomas Willis
published in 1664 his hypothesis that “megrim” was due to dilatation of blood vessels within the head
(the first enunciation of a vascular theory) [19,20]
Initially, acute migraine-specific management was based on the vascular model of headache advanced
by Wolff and Graham after their seminal article in 1938 linking migraine to vasoconstriction; thus,
vasoconstricting agents were sought that could terminate an attack. As a result, ergot preparations
were developedand were efficacious, but with significant side effects.
Migraine Historical timeline :
400 BC Hippocrates states that headaches are derived from “humors” (fluids or
vapors) circulating in the body, illness resulted from imbalances of natural
elements.

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200 AD Galen introduces the term “migraine”, which is derived from the Greek
world hemicrania.
1598 Charles Le Pois described premonitory symptoms and migraine with aura for
the first time.
1938 Graham and Wolff demonstrate the efficacy of ergotamine in aborting

migraine by constricting cerebral blood vessels.
1943 Stoll and Hoffman synthesize DHE (dihydroergotamine).
1945 Horton, Peters, and Blumenthal use DHE to treat acute migraine at the Mayo
clinic
1976 Propranolol is reported to be efficacious in migraine prevention
1991 Pat Humphrey reports the efficacy of Sumatriptan in aborting acute migraine
in human volunteers.
1993 Sumatriptan is first triptan to be FDA approved and marketed
2002 Valproic acid is FDA approved for migraine prevention
2004 Topiramate is FDA approved for migraine prevention
1.6 NATURAL HERB’S FOR MIGRAINE:
o Feverfew (Tanacetum parthenium), also known as wild chamomile and used traditionally in
the treatment of migraine and headache. The most important active compounds in feverfew are
the sesquiterpene lactones produced by superficial leaf glands, with Parthenolide considered to
be the main active ingredient. Parthenolide can also be found in other Asteraceae species, such
as German Chamomile.
o Since clinical trials have confirmed its effectiveness against headaches and migraine. Feverfew
is recommended as a migraine prophylactic.

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Tanacetum parthenium
Cannabis, or Marijuana: has been used for centuries for both symptomatic and prophylactic treatment
of migraine Not many physicians today are aware of the prominence that Cannabis drugs once held in
medical practice. Problems with quality control and an association with perceived dangerous effects
sounded the death knell for Cannabis as a recognized Western therapy.
In 1974, (Noyes and Baram) the first of several studies appeared examining issues of pain relief with
Cannabis . This article examined five case studies of patients who volitionally experimented with the
substance to treat painful conditions. Three had chronic headaches, and found relief by smoking
Cannabis that was comparable, or superior toCannabis
ergotamine tartrate and aspirin.[21]
Moringa oleifera: The Moringa oleifera belonging to family: Moringacacea which is cultivated
throughout India. The plant leave’s consist of vitamins A and C, proteins, amino acids, flavonoid,

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phenolics, glucosinoleter, isothiocynatus and thiocarbamates (niczinin A and B and niczimicin) the
leaving M.olifire had property to treat migraine.[22]
Moringa oleifera
Areca Catechu: Areca catechu belonging to family: Arecacea Which is found throughout India. The seed
mainly consist of Tannin, Alkaloids, terpenoids, flavonoids, amino acids, peptids phenols. The seeds are
Areca Catechu
showing property to treat migraine by extracting with 50% aqueous. Ethanol by cold maceration.

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The anti-inflammatory activity has been reported for Areca nut extract (Bhandare et al., 2010) and
based on the well known involvement of inflammatory processes in the development of migraine
(Conner and Grisham ;1996) it seems that the anti-inflammatory potential of ANE may be responsible
for its anti-migraine activity.[23]
Menthe piperita: Menthe piperita belonging to family: Lamiaceae. The volatile oil of menthe piperita
consist of menthol, menthone and cineole,these having anti migraine property. This oil is used by
inhalation [13]
Menthe piperita
Ocimum americanum: It belongs to family Amacea, leaf are having property of antimigraine[24]
Ocimum americanum

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Chrysanthemum Indicum: It belongs to family Astreaceca. Leaf decoction having property of
antimigraine. [25]
Chrysanthemum Indicum

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Fever few (Tanacetum parthenium) IN THE TREATMENT OF MIGRAINE
Fever few (Tanacetum parthenium):
German Chamomile have similar flowers so Feverfew (Chrysanthemum parthenium/ Tanacetum

parthenium L.) may sometimes mistake for German Chamomile (Matricaria Recutita). German
chamomile also belongs to the same Asteraceae family as Feverfew, but its use in migraine
prophylaxis is not evidenced.
The current study aims to compare the levels of bisabolol, chamazulene and Parthenolide in Feverfew
and German Camomile extracts, both from flower heads and leaves, and rationalize the use of German
chamomile leaves in anti-migraine therapy [26]
Feverfew activity does not seem to be exerted through a single mechanism. The plant extract affects a
wide variety of physiologic pathways, some of which have been already discussed, such as decrease in
vascular smooth muscle spasm, inhibition of prostaglandin synthesis and blockage of platelet granule
secretion [27]
The rationale for its long history of use in the treatment of inflammatory conditions has now been
confirmed through in vitro studies on feverfew extracts.These studies have shown that the extract
inhibits platelet aggregation; inhibits the secretion of inflammatory and allergic mediators such as
histamine and serotonin from platelets and leucocytes; and inhibits synthesis of prostaglandins in
various cells and tissues, preventing spasms of blood vessels in the head that trigger migraine attack.
The cumulative result of this activity is a reduction in the severity, duration, and frequency of migraine
headaches and an improvement in blood vessel tone.
The proper parthenolide content is essential for the activity of feverfew to take place. Feverfew
preparations used in successful clinical trials had a 0.4% to 0.66% parthenolide content, providing a
parthenolide dosage of 250 to 500mcg/day. Clinical experience has indicated that 4 to 6 weeks are
required to note a response, with continuous usage recommended for the treatment and prevention of
migraine GGG[8]

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In a more recent report, parthenolide has been studied in nitroglycerin induced Fos activation. In this
study feverfew extract with different concentrations of parthenolide and purified parthenolide are
tested on nitroglycerin induced changes in the rat brain. Parthenolide exhibited inhibitory activity
upon a subgroup of brain nuclei in response to nitroglycerin
administration. The results of the study suggest that parthenolide is the component
responsible for the biological activity of feverfew .Feverfew is available in capsule, tablet and liquid
extract forms. All the feverfew preparations are standardized to contain 0.2% of parthenolide [28]
Cultivation
Propagation of this plant is both sexual and asexual via direction or indirection methods. In
indirection method, seeds grown in outdoor bed at suitable period. Light is necessary for
germination. After regular irrigation and weeding in outdoor bed, seedlings should be transfer to the
main land at suitable time. The best time for vegetative propagation is in the fall. In asexual
propagation, plants are propagated by crown division .
T. parthenium is a long day plant, which means that 12 or more hours of light will induce the
formation of flower buds. Environmental conditions could be modified throughout the cultivation to
maximize the accumulation of key compounds. Regulation of stress in plants results in the changes
in level of secondary metabolites. When growth is reduced due to stress, more carbon becomes
available for secondary metabolism, inducing the production of some phytochemicals . It is known
that in various plants environmental stress increases the accumulation of phenolic compounds . [29]
Exposure to high visible radiation may increase the xanthophyll cycle activity and therefore
production of various secondary metabolites . Under low light intensities, ABA increases, which
regulates some processes in secondary metabolism . During cultivation and especially at the initial
stage, watering is required and is very important for T. parthenium. Water stress is another factor that
can potentially alter concentration of key compounds in medicinal plants. The plants under water
stress normally show increased accumulation of ABA which triggers changes in content of other
secondary metabolites such as phenolic, tannins, proline, polyamines and terpenoid compounds .
T. parthenium can be susceptible to aphids, miners, caterpillar and mildew. Controlling weeds in
vegetative period has important role in increasing yield, so in the first season weeds are weeding
mechanically two or three times. So far, there has not been any pest or disease observed on this plant.
.[30]

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Fertilization has an effective role in increasing yield and improves qualitative and quantitative
characteristics of the extract. Nitrogen has an important role in increasing sesquiterpenes lactones.
Adding 100 kg nitrogen per hectare causes increase in yield and content of parthenolide. Use of
parthenolide also affected the qualitative and quantitative characteristics of extract. So firstly, the
nutritive needs should be studied in the cultivation conditions. Usage of micro elements such as Mg,
Na, Mn and Cu is recommended to increase yield . [31]
History of feverfew:
In 1978, a British health magazine reported that a 68-year-old woman who had suffered from chronic
migraines since the age of 16 tried feverfew leaves with complete relief of her headaches within a few
months[32]. Since the 1980’s feverfew has become a highly popular British, French and Canadian
phytomedicine used to prevent migraine headaches, relieve menstrual cramps and treat painful
joints[33,34].
It also became a top-selling American phytopharmaceutical in the late 1990’s. Feverfew has not been
reviewed by the German Commission E. A thorough review of feverfew and migraine headaches,
written for a consumer audience is: D. Baranov (ed. S Bratman and D Kroll). Everything you need to
know about Feverfew and Migraines. Prima Publishing. 1998
Feverfew, also known as wild chamomile, has been traditionally used in the treatment of headache
and migraine. Since clinical trials have confirmed its effectiveness against headaches and migraine
. Feverfew is recommended as a migraine prophylactic .
[35]
The most well-studied and abundant group of active compounds in feverfew are the sesquiterpene
lactones produced by superficial leaf glands, with Parthenolide considered to be the main active
ingredient [36,37].
Traditionally, the herb has been used as an antipyretic, analgesic and antiinflammatory, it was also
used for allergies, nausea and vomiting [27]

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Over 45 million Americans suffer from chronic headaches; of these, 16 to 18 million suffer from migraines
annuall .It is estimated that industry loses 50 billion dollars per year due to absenteeism and medical
expenses caused by headache, and migraine sufferers lose more than 157 million workdays each year. In
excess of 4 billion dollars are spent annually on overthe-counter pain relievers for headache, many of which
prove ineffective.
Botanical classification:
Kingdom : Plantae (Plants)
Subkingdom : Trachiobionta (Vascular plants)
Super division: Spermatophyta (Seed plants)
Division : Mangliophyta (Flowering plants)
Class : Magnoliopsida (Dicotyledons)
Subclass : Asteridae
Order : Asterales
Family : Asteraceae (Aster family)
Genus : Tanacetum (tansy)
Species : Tanacetum parthenium (feverfew)
Scientific names: Tanaceti Parthenii, Tanacetum Parthenium, Chrysanthemum parthenium,

Leucanthemum Parthenium, Pyrethrum Parthenium
Common names: Altamisa, Bachelor’s Button, Featherfoil, Featherfew, Featherfoil, Flirtwort

Midsummer Daisy, Santa Maria, Mother-herb, Febrifuge plant[38]
Phytochemicals Potentially active chemical components of feverfew are as follows:
1- Sesquiterpen lactones
2- Flavonoid glycosides
3- Sesquiterpenes and monoterpenes

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4- Other components including polyacetylenes, pyrethrin, melatonin and tannins [39].
Parthenolide is the most abundant sesquiterpene lactone and is considered the most active
chemical component in feverfew [29].
MACHANISM OF ACTION
The pathophysiology of migraine is not fully understood; hence, the mechanism of action of
feverfew in migraine prophylaxis remains to be adequately defined. The alphamethylene-gamma-
lactone group of parthenolide and the lactones may provide much of the biological activity of
feverfew. As the nucleophile in biological systems is very often a thiol (sulfhydryl) group, the
activity is probably due to the alpha-methylene-gamma-lactone group acting as an alkylating agent
of such thiol residues [40]and thusdisrupting cell function. (Thiol groups, such as cysteine residues in
proteins or enzymes, are important constituents of the plasma membrane and cytoskeleton' [41].The
assembly of microtubules in the latter is known to be involved in phagocytosis and degranulation of
neutrophilsJ [42]
It had been proposed that a significant increase in serotonin release from platelets
triggers the complex chain of events leading to a migraine attack''[42] and that migraines are caused by
abnormal platelet activity and abnormal serotonin metabolism."[43] However, this theory no longer
has widespread currency.
!n accordance with this earlier theory, the fact that feverfew interacts with the protein kinase C
pathway, causing an inhibition of granule secretion from platelets, suggested an anti-migraine effect
and polymorphs(antiarthritic effect).[44]
It has been demonstrated that this effect is due to the parthenolide and other sesquiterpene lactones
in feverfew,'[45] and neutralization of sulfhydryl groups either inside or outside the cell Is
involved.''[46]' Another theory is that feverfew has anti-inflammatory activity.
In one study parthenolide inhibited eye I o-oxygen a se (which converts arachidonic acid to
prostaglandins) in vitro.^[47]'^ Parthenolide also inhibited the expression of inducible cyclo-
oxygenase and proinflammatory cytokines in macrophages, which correlated with the inhibition of
mitogen-activated protein kinases. The alpha-methylenegamma-lactone group conferred the
inhibitory activity.-[48] However, aqueous extracts of whole plant and leaf inhibited prostaglandin
biosynthesis but did not inhibit cycio-oxygenase.[49] Parthenolide did not inhibit cyclooxygenase

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activity in vitro with enzyme derived from sheep seminal vesicles[50] Other evidence suggests that
sesquiterpene lactones, including parthenolide, inhibit the release of arachidonic acid from
membrane phospholipid stores rather than its conversion into thromboxane B2 via the cyclo-
oxygenase pathway.[51] Chloroform extract of feverfew evoked changes in the metabolism of
arachidonic acid that were similar to those observed in glutathlone-depleted platelets.' [52] It also
inhibited uptake and liberation of arachidonic acid into or from platelet membrane phospholipids ,
which may be the result of altered cytoskeletal-membrane interaction .[42]Sulfhydryls (SH) groups
[53]
are essential for phospholipase A, activity (and the liberation of arachidonic acid), [54]which may have
been affected by feverfew.-[53] Chloroform extracts of feverfew produced dose-dependent inhibition
of the generation of thromboxane B2 and leukotriene B4 by stimulated leucocytes. The activity was
due to other lactones as well as sesquiterpene lactones,- [55] However, it is uncertain whether any of
these anti-inflammatory effects are relevant in humans at the doses of feverfew typically used.
OR
In 1985, it was reported that extracts of feverfew inhibited the release of [87]
inflammatory
substances; serotonin from platelets and prostaglandin from white blood cells[88].
Both are thought to contribute to the onset of migraine attacks and perhaps even to play a role in
rheumatoid arthritis.By inhibiting these amines as well as the production of histamine, the herb
controls inflammation that constricts the blood vessels in the head, and prevents blood vessel spasms
which may contribute to headaches. [89]
Other possible mechanisms are that it suppresses production of prostaglandin,thromboxane and
leukotriene, constituents prevent formation of inflammatory mediators by inhibiting cellular
phospholipases and release of arachidonic acid from cell membrane,
and extracts inhibit platelet aggregation.There has not been proof of these pharmacologic actions to
have an effect on migraine prophylaxis.This remains to be.unclear [87]
Dosage forms, recommended doses, duration:
Feverfew is supplied in a capsule, tablet, tincture, or liquid extract forms crude leaf, powder or seed
dosage forms. Feverfew supplements with clinical studies contain a standardized dose of parthenolide. The
Canadian Health Protection Branch allows the following dose for the prophylaxis of migraines in
adults: 125-250mg daily of dried feverfew leaf preparation containing a minimum of 0.2%
parthenolide.

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MICROMEDEX alt med PDA: 200-250mg daily capsule or 1 fresh leaf daily.Feverfew is considered
safe when used short term for no more than 4 months. The safety long term is unknown [56]
Pediatric
Feverfew should not be used in children younger than 2 years. In older children, adjust the
recommended adult dose to account for the child's weight. Most herbal dosages for adults are
calculated on the basis of an average of 150 lb (70 kg) adult. Therefore, if the child weighs 50 lb
(20–25 kg), the appropriate dose of feverfew for this child would be 1/3 of the adult dosage. [29]
Adult
For migraine headaches: Take 100–300 mg, up to 4 times daily, standardized to contain 0.2–0.4%
parthenolides. Feverfew may be used to prevent or to stop a migraine headache. Feverfew
supplements may also be CO extracted. For these, take 6.25 mg, 3 times daily, for up to 16 weeks.
For inflammatory conditions (such as arthritis): 60-120 drops, 2 times daily of a 1:1 w/v fluid
extract, or 60-120 drops twice a day of 1:5 w/v tincture.[57–59]
FEVERFEW INTERACTION
Feverfew may alter the effects of some prescription and non-prescription medications. If you are
currentlybeing treated with any of the following medications, you should not use feverfew without
first talking to your health care provider.[60]
Blood-thinning medications- Feverfew may inhibit the activity of platelets (a substance that plays a
role in blood clotting), so individuals taking blood-thinning medications (such as aspirin and
warfarin) should consult a health care provider before taking this herb.[61]
ADVERSE REACTIONS

22
Adverse effects of patients administered feverfew 50 mg/day (roughly equivalent to 2 leaves) during 6 months
of continued treatment were mild and did not result in discontinuation. Four of 8 patients taking the plant had
no adverse effects. Heart rate increased dramatically (by up to 26 beats/min) in 2 treated patients. There were
no differences between treatment groups in laboratory test results. Patients who switched to placebo after
taking feverfew for several years experienced a cluster of nervous system reactions (eg, headaches, insomnia,
joint pain, nervousness, poor sleep patterns, stiffness, tension, tiredness) along with muscle and joint stiffness,
often referred to as “postfeverfew” syndrome[ 62,60] In a larger series of feverfew users, 18% reported adverse
effects, the most serious being mouth ulceration (11%). Feverfew can induce more widespread inflammation
of the oral mucosa and tongue, often with lip swelling and loss of taste. Dermatitis has been associated with
this plant.[62,63,64]
TOXICOLOGY
No studies of chronic toxicity have been performed on the plant and the safety of long-term use has not been
established. Pregnant women should not use the plant because the leaves have been shown to possess
potential emmenagogue activity. It is not recommended for lactating mothers or for use in children .[65]
One study evaluated the potential genotoxic effects of chronic feverfew ingestion in 30 migraine sufferers.
Analysis of the frequency of chromosomal aberrations and sister chromatid exchanges in circulating
lymphocytes from patients who ingested feverfew for 11 months found no unexpected aberrations,
suggestingthat the plant does not induce chromosomal abnormalities .[66]

23
2. LITERATURE REVIEW
 Knowledge of the epidemiology of headache disorders has been sparse. The main
problem in any study of the epidemiology of headaches has been defining the disease
entities, because there are no laboratory correlates or other objective markers. Previous
classification systems lacked precision because they included ambiguous expressions
and were nonoperational, which resulted in vague criteria (Gowers 1888; Freidman
and Merritt 1959; Ad Hoc Committee on Classification of Headache 1962; World
Federation of Neurology 1970)
 The chemistry of feverfew is now well defined. Chemotype and geographical
distribution of seeds are the varying factors for the constituents of P. hysterophorus
(Blumenthal et al., 2003) Demonstrated that [69]. More than 45 sesquiterpene
lactones were identified from leaves and flower among them the major is sesquiterpene
lactone parthenolide, which is up to 0.9% of total constituents (Anonymous, 2003;
Fugh-Berman, 2003). Twenty-three compounds, representing 90.1% or more of the
volatile oils, have been identified from P. hysterophorus (Pareek etal., 2011)[36]. The
toxic and inhibitory constituents contained by all parts (stem, leaves, leaf hair, flower,
pollen grain) of P.hysterophorus .
 In 1974, the first of several studies appeared examiningissues of pain relief with
Cannabis (Noyes and Baram,1974) Demonstrated that [67].
This article examined five
case studies of patients who volitionally experimented with the substance to treat painful
conditions. Three had chronic headaches, and found relief by smoking Cannabis that
was comparable, or superior to ergotamine tartrate and aspirin. One subsequent study of

24
Cannabis pertained to pain tolerance in an experimental protocol (Milstein et al., 1975)
[68].
A statistically significant increase in pain threshold was observed after smoking
Cannabis in both naive (8%increase) and experienced subjects (16% increase).Another
trial involved oral THC in cancer patients (Noyes et al., 1975a). They observed a trend
toward pain relief with escalating doses significant to the P , 0.001 level. The peak effect
occurred at three hours with doses of 10 and 15 mg, but not until 5 h after ingestion of
20mg.
 It is apparently a global disorder, occurring in all races, cultures, and geographical locations.
Current figures suggest that 18 percent of women and sixof men suffer from migraine and
those numbers are increasing [ 70].
The worldwide prevalence of headache for all age-group is
considered to be more than 47%, and of migraine is 10.3% [71] and is more prevalent in females
than in males (15-18% vs. 6%)]70]. The incidence of migraine begins earlier in males than in
females, and Migraine with Aura begins earlier than Migraine without Aura 72]. For both men
and women, the prevalence of migraine rises throughout early adult life and falls after midlife.
In girls and women, the rate almost triples between age 10 and 30 years [73].
 S heptinstai.L (1992) Demonstrated that A bioassay based on inhibition of the secretory
activity of blood platelets by extracts of feverfew in comparison with parthenolide was also
used. Similar results were obtained for all three physicochemical assays and also for the
bioassay. Thus, different methodologies yield consistent values for parthenolide content of
feverfew preparations. Parthenolide appears to be mainly responsible for the antisecretory
effects of extracts of feverfew.[42]
 De Weerdt CJ, Demonstrated that (1996);.A team of Dutch scientists who had been very active
in the field of feverfew research tested the efficacy of a standardized extract for the prevention of
migraine headaches. In a randomized, placebo-controlled,double-blind, crossover design, 50
patients who had never taken feverfew before andexperienced at least one migraine attack per
month were followed for four months of active treatment and four months of placebo. Active
treatment consisted of 143 mg per day of a granulated ethanolic extract of feverfew containing
0.5 mg of parthenolide and corresponding to about 170 mg of original dried herb. The feverfew
preparation used in this study did not exert any significant preventative effect on the frequency
of migraine attacks, although patients seemed to have a tendency to use fewer analgesic drugs
while they were using feverfew.[74]

25
 Milne RD, (1997) Demonstrated that.There are many types of headaches, each with its own set
of causes, symptoms, and points of pain. The more common types include tension, cluster,
migraine, allergy/sensitivity, sinus, trauma, and eyestrain headaches. However, all headaches are
related in that each one is a response to a metabolic, structural, and/or emotional imbalance.
Headaches may be triggered by factors that fall into 8 broad categories: dietary sensitivities,
environmental irritants, hormonal imbalances, digestive disturbances, autoimmune disturbances,
lifestyle factors, structural imbalances, and mental stress[3]
 In 1988, explicit diagnostic criteria for all headache disorders were introduced by the Headache
Classification Committee of the International Headache Society (IHS; Headache Classification
Committee 1988), Demonstrated that opening up new opportunities for valid epidemiological
headache research. Another problem is that most previous studies have been conducted on
selected groups of patients, e.g., from hospitals, clinics, or general practitioners.
 The Atharva Veda of India, dated to between 1400 and 2000 BC referred to a sacred grass,
bhang, and medicinal references to Cannabis were cited by Susrata in the sixth to seventh
centuries AD (Chopra and Chopra, 1957) Demonstrated that [75]
and included indication for its
use for headache .
 Several studies have documented that only a minority of headache sufferers ever consult a doctor
for their headaches (Linet et al. 1989; Stewart et al. 1989; Celentano et al. 1992; Köhler et al.
1992; Lipton et al. 1992; Rasmussen et al. 1992). Demonstrated that Nonconsulters are likely
to differ from those who seek medical attention. It is therefore essential that studies on the
epidemiology of headache are carried out in representative general populations. [70]
 (Kalodera et al. 1997). Demonstrated that The analysis of feverfew oil showed the presence of
many monoterpenes as α-pinene, camphene, β-pinene, sabinene, myrcene, α-fellandrene, α-
terpinene, p-cymene, γ-terpinene, terpinolene, terpinen-4-ol and α-terpineol. Among them, the
oxidized monoterpenes are very well represented especially camphor, trans-chrysanthenyl acetate,
linalool, linalyl acetate and bornyl acetate. The essential oil is mostly composed of camphor and
trans-chrysanthenyl acetate amounting up to 70% of the whole oil content. These are the main
components of the oil. Among other monoterpenic components, there is a greater amount of p-
cymene (4.77%), linalool (2.28%) and camphene (1.96%). Sesquiterpenic lactones are not
qualitatively or quantitatively present as monoterpenes. Among the sesquiterpenic compounds

26
there are: β-caryophyllene (1.96%), trans-β-farnesene, germacrene (1.49%) and δ-cadinene. The
phenyl propanic compound eugenol is also present (1.09%)
 William EM. et al.(1998). Demonstrated that Migraine is the most common type of headache
leading patients to consult a physician. For most patients, a combination of non-pharmacologic
and pharmacologic interventions should be used to control the headache disorder. Many of the
non pharmacologic therapies are based on the theoretic concept of migraine as resulting from
neurochemical instability within the brain. These approaches, which are often
“biobehaviouristic,” may be complementary or adjunctive to pharmacologic treatment or may
provide an alternative to it.[76]
 Ethan Russo (1998) Demonstrated that Cannabis, or marijuana, has been used for centuries
for both symptomatic and prophylactic treatment of migraine. It was highly esteemed as a
headache remedy by the most prominent physicians of the age between 1874 and 1942,
remaining part of the Western pharmacopoeia for this indication even into the mid-twentieth
century. Current ethnobotanical and anecdotal references continue to refer to its efficacy fo this
malady, while biochemical studies of THC and anandamide have provided a scientific basis for
such treatment. The author believes that controlled clinical trials of Cannabis in acute migraine
treatment are warranted. 1998 International Association for the Study of Pain.Published by
Elsevier Science B.V.[21]
 In 1941, Cannabis preparations were dropped from the United States Pharmacopeia (U.S.P.), but
the following year, the editor of the Journal of the American Medical Association still advocated
oral preparations of Cannabis in treatment of menstrual (catamenial) migraine (Fishbein,1942)
[85].
Demonstrated that This practitioner seemed to prefer Cannabis to ergotamine tartrate, which
remains in the migraine armamentarium, some 55 years later. Thus, Cannabis was touted in eight
consecutive decades in the mainstream Western medical literature as a, or the, primary treatment
for migraine. As late as 1957, despite governmental controls in that country, Cannabis drugs
retained a role in the indigenous medicine of India (Chopra and Chopra, 1957), [75]
and other
countries.
 William EA. et al (1998) Demonstrated that has developed guideline for the non pharmacologic
management of migraine in clinical practice which includes the application of cold or pressure to

27
the head, reduction of activity and of sensory input in a quiet or dark environment and attempts
to sleep and are supplemented by the use of pharmacologic therapies when not adequate in
isolation. Relaxation therapy, hypnosis, transcutaneous electrical stimulation, acupuncture, and
occipital or supraorbital nerve blockade have also been used in the acute situation and are
considered. [76]
 J. D. Bartleson ,etal. Demonstrated that (2010) Migraine is a common intermittently
debilitating neurovascular disorder that affects younger adults, especially women.The diagnosis
is generally made based on clinical criteria, with neuroimaging used in some cases to exclude
secondary causes of headache. The incidence of migraine peaks between 15 years and 24 years
of age,1 and the prevalence is highest among persons between the ages of 35 and 45 years. In
the United States, the one-year prevalence rate of migraine is estimated to be 17.6% in women
and 5.7% in men and the cumulative lifetime incidence of migraine is 43% in women and 18%
in men.1 Evidence suggests that migraine is underdiagnosed. One study reported that one-fourth
of patients whose headaches met the criteria for migraine were not diagnosed as having this
condition; another found that approximately half of patients with migraine were undiagnosed.
Even when diagnosed, migraine is often undertreated.[10]
 (Preeti Jaiswal, 2011). Demonstrated that The main constituents of the areca nut are
carbohydrate, fats, fibre, polyphenol including flavonoids and tannins, alkaloids and minerals.
Alkaloids present are arecoline, arecaidine, arecolidine, guvacine, guvacoline, isoguvacine,
norarecaidine and norarecoline. Of all these alkaloids, arecoline is physiologically most
important .[77]
 S.Khan et al., (2011) Demonstrated that reportedAreca catechu extract and its aqueous fraction
possess anti-inflammatory and analgesic activities mediated possibly through cyclooxygenase and
lipoxygenase inhibitory pathways, and by degradation and/or inactivation of prostaglandin E2
(PGE2). These findings suggest that the areca extract and its aqueous fraction have good
correlations with the medicinal use of Areca catechu in inflammatory disorders in the Unani
(Greco-Arab) system of medicine (Shagufta Khan, 2011)
 (Amol Bhandarea, 2011) Demonstrated that.The Areca nut extract inhibited the plasma protein
extravasation and development of inflammation within dura mater, gives the sufficient evidence for
its anti-migraine activity via vascular theory of migraine .
 Kanchan P Upadhye et al., 2012 Demonstrated that oleifera leaf juice.The Moringa oleifera
belonging to family Moringacacea which is cultivated throughout India. The plant leave’s consist of

28
vitamins A and C, proteins, amino acids, flavonoid, phenolics, glucosinoleter, isothocynatus and
thiocarbametes (niczinin A and B and niczimicin) the leaving M.olifire had property to treat
migraine[22]
 Vivek Sharma et al. (2012) Demonstrated that Headaches have afflicted man throughout history,
and Migraine is a common, but under diagnosed and under treated type of headache that has a
strong social impact, influencing both quality of life and work productivity. Stress, food allergies,
neuro endocrine imbalances and nutritional deficiencies all may contribute to migraine attacks.
Several mechanisms have been implicated in migraine patho physiology including inflammation,
mitochondrial dysfunction, abnormal neuronal excitability and vascular events[1]
 G. D’Andrea (2014) Demonstrated that There is a growing body of evidence supporting the
efficacy of various ‘‘complementary’’ and alternative medicine approaches in the management of
headache disorders. A lternative or complementary modes of treatment often lack scientific proof of
efficacy. Given the side effects of traditional prescription medications, there is an increasing
demand for ‘‘natural’’ treatment of headaches. Many of these complementary modes are
inexpensive, harmless, and possibly effective. These treatment modalities include ‘‘herbal
therapy’’. Therefore, it is important that headache clinicians and researchers treating adult and
pediatric migraines explore therapies that are safe, effective and affordable, using them as
alternative monotherapy option or as ‘‘add on’’ preventive therapy. As for mechanisms behind
botanical treatments, the lack of funding for studying these agents will continue to retard progress
in this area as well, but hopefully the future will bring more concentrated effort
 Dorota Talarska,etal.(2014) Demonstrated that On account of headache frequency emerging as
the most significant influencing factor, it is of the utmost importance to inform patients of the value
of taking prophylactic measures. Central to this is the identification of factors that trigger the onset
of migraines. This approach would greatly aid the individual choosing the appropriate treatment,
either pharmacological or others.[78]
 T. Roopavani etal.(2014). Demonstrated that Through this column few herb’s that having
traditional important explained according to ethno botanical survey. The herbs are mostly
indigenous to south India that is locally used. The task is that the herbal extract of different plant’s
are used traditional for antimigraine curing, treatment, prevention. The Migraine is a challenging
problem for healthcare physician. The present an attempt is made for explore of some hidden
solution for migraine which are using our ancient age’s.[2]

29
 P. hysterophorus was reported to inhibit granule secretion in blood platelets, which is related with
the etiology of migraine (Heptinstall et al., 1985)[79]. Demonstrated that A randomised,double-
blind, placebo-controlled trial for three months successfully controlled migraine in 17 patients by
eating raw feverfew leaves (Johnson et al., 1985).Another randomised, double–blind, placebo–
controlled trial demonstrated lowering the migraine pain intensity significantly during powdered
leaves(parthenolide 0.2%) 100 mg daily for 60 days administration in 57 patients (Palevitchet al.,
1997) [59]. 24% reduction of migraine attack in 72 patients was observed after P.hysterophorus
treatment (70–114 mg P. hysterophorus equivalent to 2.19 μg parthenolide; one capsule daily) in
another randomised double–blind, placebo– controlled, crossover trial (Murphy et al.,1988) [80].
The above studies suggest that the preparations are admirable in preventing migraine but further
well–designed clinical trials are required to establish the beneficial effects of P. hysterophorus for
migraine prophylaxis.
 Anti-Inflammatory Activit Oral administration 10, 20, 40 mg/kg of body weight of P. hysterophorus
extract led to significant antinociceptive and anti-inflammatory effects against acetic acid induced
writhing in mice and carrageenaninduced paw edema in rats, respectively (Jain and Kulkarni, 1999)
[81]. 200mg/kg of body weight of fresh leaves ethanolic extract exhibited high degree anti-
inflammatory incarrageenan induced paw edema rats (Pandey et al., 2012) [82]. Demonstrated that 1,
2 mg/kg of bodyweight parthenolide administration alsoproduced antinociceptive and anti-inflammatory
effects (Jain and Kulkarni,1999)[81]. The anti-inflammatory property may be due to an inhibitor of
cellular phospholipases, which prevents release of arachidonic acid in response to appropriate
physiological stimuli (Makheja and Bailey,1982).
 shree vidya p, etal.(2013) headache is most common health problem experienced by mankind that
around 40% are suffering from migraine which results in severe disabling condition. WHO has
ranked migraine as number 19 among all disease worldwide causing disability. Migraine can be
defined as benign, reoccurring syndrome of headache, nausea, vomiting or other syndrome of
neurological dysfunction. [83]
 Mohammad Taghi Moradi et al( 2014) Demonstrated that Migraine is a disabling and very
common health problem. This review article reported the plants used to treat migraine in traditional
culture and ethnobotany of different regions of Iran. The key words such as ethnopharmacology,
ethnobotany, ethnomedicine, phytopharmacology, traditional medicine, phytomedicine, and Iran,
combined with migraine and headache, were used to search for relevant materials in Web of
Science, PubMed,Scopus, Islamic World Science Citation Center, and Magiran. Twenty two

30
medicinal plants from 16 families are used, according to Iranian traditional medicine, to treat
migraine specifically. Most plants reported in this study were analgesic and anti-inflammatory,
affecting the inflammation and cortical vascular contractile dysfunction.Because of common use of
traditional medicinal plants and wide acceptance of herbal medicine and traditional medicine, more
comprehensive studies should be done in pharmacy and pharmacology areas to inform
pharmaceutical industries.[5]
 AC Lyngberg, (2005) Demonstrated that Pharmaceutical companies of Iran are currently producing
herbal drugs that are effective on migraine and the associated symptoms such as depression, so that
herbal drugs may be used as alternatives to chemical drugs. Various anti-migraine herbal drugs are
being produced in Iran, including tanamigrain, antimigraine drop, and hypiran drop. All of these
herbal drugs have been derived from Iran traditional medicine and have recently become
commercially available. However, many of the medicinal plants identified in this study have not
been sufficiently investigated for anti-migraine effects in clinical trials. From pathophysiological
perspective, migraine is the final outcome of interaction of different factors such as genetic
predisposition, susceptible central nervous system, hormonal factors, and sequence of neurovascular
events due to release of pain-causing inflammatory substances around vessels and nerves, with
varying significance in different people. Neurological events of migraine, are caused by
cerebrovascular spasm, and the migraine pain is due to the subsequent dilation of extracranial
arteries.[84]
 Pourianezhad F et al(2016) Demonstrated that Medicinal plants respond to environmental
conditions and different environmental conditions affect medicinal plants’ quality. The active
ingredients in feverfew are sesquiterpene lactones, mainly parthenolide. The highest parthenolide
levels were seen in the plants that received low-water regimens and light enhanced accumulation of
parthenolide immediately before harvest. The parthenolide has multiple pharmacologic properties
such as anticancer, anti-inflammatory and cardiotonic. In Iran, this plant needs to be cultivated
because of its importance as a medicinal plant and various therapeutic uses.[29]
 Bhupendra et al. (2017). Demonstrated that Migraine is a common disabling condition mostly in
adult population and shows female predominance. Unilateral throbbing type moderate to severe
intensity headache is a common manifestation of the migraine though it may present with varied
presentation. Even though there is rapid advancement in the knowledge of path physiology leading
to development of novel treatment, evidence based treatment for migraine specially in developing
nations is still unmet needs.[4]

31
 Rome, Italy. ( 2017) Demonstrated that A new phototherapy combination of Tanacethum
Parthenium (150 mg), 5-Hydroxy tryptophan (20 mg) and Magnesium (185 mg) (Aura stop) is
now available for migraine patients. The three components may tackle the main mechanisms
involved in the pathophysiology of migraine with aura: Cortical Spreading Depression, sensitization
of trigeminal vascular system, central sensitization. The purpose of this open study was to evaluate
the efficacy of the combined action of Tanacethum Parthenium, 5-Hydroxy tryptophan and
magnesium in the reduction/disappearance of the aura phenomenon and reduction of its disability
when taken at the aura onset.[69]
.
 Bryson C.lochte, et al.(2017) Demonstrated that Headache disorders are common, debilitating,
and, in many cases, inadequately managed by existing treatments. Although clinical trials of
cannabis for neuropathic pain have shown promising results, there has been limited research on its
use, specifically for headache disorders. This review considers historical prescription practices,
summarizes the existing reports on the use of cannabis for headache, and examines the preclinical
literature exploring the role of exogenous and endogenous cannabinoids to alter headache
pathophysiology. Currently, there is not enough evidence from well-designed clinical trials to
support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results,
as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such
trials are needed to determine short- and long-term efficacy for specific headache types,
compatibility with existing treatments, optimal administration practices, as well as potential risks.
 Ashar M. Farooqi(2018) Demonstrated that ACM(Acute Confusional Migraine) is a migraine
variant that is not well understood. While it is true that ACM can be recognized by its unique
characteristics, some of its symptoms and signs overlap with non-headache features of migraine
with and without aura. The lack of specific classification criteria may lead to diagnostic uncertainty,
excessive diagnostic testing and delays in adequate treatment. Prospective studies are needed to
further study this disorder and its association with other migraine forms. Inclusion in the appendix
of ICHD-3_ criteria is necessary for better characterization through research efforts.
 Snezana Agatonovic-Kustrin etal. (2015) Demonstrated that The purpose of this study was to
compare and analyse active components in feverfew and chamomile using High Performance Thin
Layer Chromatography as the analytical method. Both plants belong to the same Asteraceae family
and feverfew is sometimes mistaken for German chamomile due to similar Feverfew leaves have
been traditionally used in the treatment of migraine, with Parthenolide regarded as the primary

32
active ingredient. On the other hand, bisabolol and chamazulene have anti-inflammatory properties,
and are the main active components in German chamomile essential oil which is obtained by steam
distillation of flower heads.Bisabolol and chamazulene were present in higher concentrations in
flowers and in leaves from flowering German chamomile. Parthenolide was present in higher
concentration in leaves. Parthenolide and chamazulene are both terpenoids, derived from the same
sesquiterpene precursor, farnesyl diphosphate, via two different biosynthetic pathways.
Our study of Feverfew and German chamomile suggests that the Parthenolide pathway is
favoured inleaves, while formation of matricin and bisabolol is favoured in flowers. Anti-
inflammatory activity of chamazulene and the presence of Parthenolide could explain and justify
the use of chamomile in the treatment and prevention of migraine.[26]
Dipankar Chandra Roy, etal.(2013) Demonstrated that Parthenium hysterophorus, members of

the Asteraceae family is a noxious weed in America, Asia, Africa andAustralia. P. hysterophorus
confers many health benefits, viz remedy for skin inflammation, rheumatic pain, diarrhoea, urinary
tract infections, allergies,asthma, dizziness, nausea, vomiting, neuralgia. This plant traditionally
used for the treatment of fevers,migraine headaches.[86]
]
2.1 PREVALENCE AND FREQUENCY:

 M i g r a i n e Previous estimates of the prevalence of migraine range from 3 – 4% to about 35%
(Brewis et al. 1966; Nikiforow 1981), a variation due largely to differences in definitions and
methodologies. Two European studies (Rasmussen et al. 1991; Henry et al. 1992), two studies
from the United States (Breslau et al. 1991; Stewart et al. 1992), and one from Canada (Pryse-
Phillips et al. 1992; Edmeads et al. 1993), all employing the operational diagnostic criteria of the
IHS (Headache Classification Committee 1988; have reported congruent prevalence figures for
migraine in adults.
 In Denmark, a random sample of 1000 men and women aged 25- 64 was drawn from the National
Central Person Registry of all Danish residents. Headaches were classified according to a
physician-conducted diagnostic interview and a neurologic examination using the IHS diagnostic
criteria. All members of the sample were invited to a general health survey with focus on headache
disorders. The participation rate was 76%, and information about a further 20% was obtained by
telephone interview. The survey showed a lifetime prevalence of migraine of 16%: 8% in men and

33
25% in women (a male:female ratio of 1:3). The one-year period prevalence of migraine was
10%:6% in men and 15% in women (Rasmussen et al. 1991).
 Analyzing migraine with and without aura separately, we found that the one-year period
prevalence of migraine without aura (previously called common migraine) was 6% and the
prevalence of migraine with aura (previously called classic migraine) was 4% (Rasmussen and
Olesen 1992a).
 The prevalence of migraine was found to be higher in age group 20-50 years with highest ranging
between >30-<40 year figure1. Around 90% of the patients were non vegetarian and 155 (38%)
patients had family history of headache .detail of prior treatment of migraine patients indicated
that 231(57%) patients were totally dependent on allopathic medicine,167(41%) patients has tried
both allopathic and alternative medicine such as Homopathic,Unani,Sidha,ayurvedic and
naturopathy etc. and eight(2%) were totally dependent on alternatively medicine .it was found that
exertion, lack of sleep and hunger were the most important factor for aggravating migraine ,and
details of other were given in figure 2. [90]

34
3. OBJECTIVE
As many of the plants reported in this study are analgesic and anti-inflammatory and contain effective
analgesic, anti-inflammatory compounds, their effects in treating migraine may be due to their analgesic,
anti-inflammatory property. Most of these plants were from Apiaceae, Asteraceae, Hypericaceae,
Lamiaceae and Rosaceae families which contain phenolic compounds and can exert great anti-
inflammatory as well as antimigraine effects.
4. FUTURE PROSPECTIVE
This study used a multi-stage process. The first stage included concept identification research through
literature review, patient-reported outcome (PRO) instrument content review, and clinician interviews, and
resulted in a list of concepts relevant to understand the migraine experience. These results informed the
design of the subsequent concept and stage that involved qualitative interviews of adults with migraine to
understand their experiences.
Information from these two stages was used to develop a conceptual disease model (CDM) of the migraine
experience. This CDM was used to identify concepts of interest (COI) to evaluate patient-relevant
outcomes for assessing treatment benefit of migraine prophylactics.

35
In the final stage, existing PRO instruments were reviewed to assess coverage of concepts related to the
selected COI.
The Core Outcome Set for Headache (COSH) study is seeking to better understand the outcomes that
matter most to people who experience headache, to clinicians (including doctors and specialist nurses),
policy makers and researchers, with a view to reaching agreement on a small group of outcomes (that is, a
‘core outcome set for headache’) that should be included, as a minimum, in all future headache studies.
Participating in the COSH study will involve completing of up to three on-line questionnaires over a period
of four months. The questionnaires will be sent to you via email. Each questionnaire will ask you to think
about the aspects of health you think should be assessed in all headache research studies. You will be asked
to rate the importance of each outcome for inclusion in future headache research.
We are inviting people with a history of headache,clinicians and health professionals with a special interest
in headache, and researchers involved in headache trials to complete the questionnaire.
CONCLUSION
Migraine is common cause of headache, focusing on the extracts and their active constitutes of medicinal
plant used in the treatment of migraine . Researchers should conduct studies on the plants from these
families whose therapeutic effects on migraine have not been investigated to date, and perform clinical
trials to develop anti-migraine herbal drugs and make them commercially available.
Cannabis, even when abused, has mild addiction potential, and seems to be safe in moderate doses,
particularly under the supervision of a physician.
More research is being conducted on Tanacetum parthenium important herb. Much more research is
conducted by successful traditional uses of the this plant. In the future, we will know how the plant can
best be used for health benefits. Consumers who use feverfew for helping with migraine should discuss this
possibility with a health care practitioner, and look for standardized products with predictable results.

36
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Sciences, 5(4): 2083- 2084
3.. RD, Milne More B, Goldberg B. An Alternative Medicine Definitive Guide to Headaches.
Tiburon CA: Future Medicine Pub; 1994
4. Bhupendra et al.(2017). Migrane. European Journal of Biomedical AND Pharmaceutical

sciences,4(4),226-230.
5. Mohammad Taghi Moradi et al. The most important medicinal plants effective on migraine:A
review of ethnobotanical studies in Iran. Der Pharma Chemica, 2016, 8 (2):462-466
6 SA, Kulkarni RA, Rege NN Dahanukar. Pharmacology of medicinal plants and natural products.
Indian. J. Pharmacol. 2000; 32: S81-S118
7.Naveen D., & Praveen kumar T(2014). Ayurvedic Resolution to Migraine. J Homeop Ayurv Med,
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MIGRAINE

ABHILASHI COLLEGE OF PHARMACY

SUPERVISED BY: SUBMITTED BY:

Vinayaka College Of Pharmacy

Vinayaka College Of Pharmacy

Vinayaka College Of Pharmacy

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Subtypes and Subforms of Migraine

Migraine without aura Migraine with aura

Childhood periodic syndromes that

Retinal migraine Complications of migraine

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Criteria for Diagnosing Migraine

Migraine without aura

Typical aura with migraine headache

Vinayaka College Of Pharmacy

2. Cortical Spreading Depression

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3. CORTICAL HYPEREXCITABILITY IN MIGRAIN

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1.3 CLINICAL FEATURE:

 Allergic reactions and allergies

 Psychological triggers like emotional stress

 Irregular sleep or changes in sleep pattern

 Physical triggers like birth control pills, menstrual cycle fluctuations,

Vinayaka College Of Pharmacy

Migraine Historical timeline :

Vinayaka College Of Pharmacy

1938 Graham and Wolff demonstrate the efficacy of ergotamine in aborting

1943 Stoll and Hoffman synthesize DHE (dihydroergotamine).

1976 Propranolol is reported to be efficacious in migraine prevention

1993 Sumatriptan is first triptan to be FDA approved and marketed

2002 Valproic acid is FDA approved for migraine prevention

2004 Topiramate is FDA approved for migraine prevention

1.6 NATURAL HERB’S FOR MIGRAINE:

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Vinayaka College Of Pharmacy

Vinayaka College Of Pharmacy

Vinayaka College Of Pharmacy

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Fever few (Tanacetum parthenium):

German Chamomile have similar flowers so Feverfew (Chrysanthemum parthenium/ Tanacetum

Vinayaka College Of Pharmacy

Vinayaka College Of Pharmacy

Vinayaka College Of Pharmacy

Subkingdom : Trachiobionta (Vascular plants)

Super division: Spermatophyta (Seed plants)

Division : Mangliophyta (Flowering plants)

Family : Asteraceae (Aster family)

Species : Tanacetum parthenium (feverfew)

Scientific names: Tanaceti Parthenii, Tanacetum Parthenium, Chrysanthemum parthenium,

Common names: Altamisa, Bachelor’s Button, Featherfoil, Featherfew, Featherfoil, Flirtwort

Phytochemicals Potentially active chemical components of feverfew are as follows:

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Vinayaka College Of Pharmacy

Dosage forms, recommended doses, duration:

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Vinayaka College Of Pharmacy