Headache Treatments By Native Peoples of the
Ecuadorian Amazon:
A Preliminary Cross-Disciplinary Assessment



Ethan B. Russo, M.D.
Deparment of Neurology, Western Montana Clinic,
Box 7609, 515 W.Front St., Missoula, MT 59807 (U.S.A.)

Headache, specifically migraine, is an extremely frequent and debilitating syndrome with worldwide prevalence, including indigenous cultures of Amazonia. This paper considers headache as perceived within the medical philosophy of 5 Indian tribes of the Ecuadorian Amazon Basin. Their ethnobotanical treatments for headache are examined, along with the limited available biochemical assay data. This information is analyzed by means of an Ethnopharmacology Rating Scale. Suggestions are offered as to methods of biochemical analysis that may be fruitful in assessment of potential clinical headache remedies. Key among these is the screening of ethnobotanical samples for serotonin receptor activity. The potential may exist for the discovery of more effective, less toxic headache drugs, as well as for the development of a new industry for the local economy that could promote conservation of an endangered ecosystem.


Key Words: headache; migraine; ethnobotany; psychopharmacology; serotonin; Amazonia

Introduction
Headache, and specifically migraine, are afflictions that have plagued mankind since time immemorial. Various epidemiologic studies have confirmed the prevalence of headache worldwide, among virtually all cultures studied (Linet and Stewart, 1984; Ziegler, 1990). Reasonable estimates of headache prevalence in a given population are difficult, due to the many subjective factors operative with headaches, the lack of objective testing parameters, as well as daunting problems in its classification. These estimates have varied widely but would include up to thirty percent of some populations.

Many neurologists, the author among them, consider most paroxysmal headaches
to be of migrainous etiology with the previous concept of "tension or muscle-contraction headache" being included on a continuum of migraine pathophysiology (Featherstone, 1985). Silberstein observes that "...Neither the vascular theory of migraine nor the muscle contraction theory of tension headache are considered viable any longer...", and additionally, "...Primary headache may now be viewed as a continuum between tension-type headache and migraine, measured by differences in severity..." (Silberstein, 1992). If true, headache prevalence is all the more widespread. Although headache has been a less attractive topic for government-funded research due to its lack of attributable mortality, the morbidity incurred by this mysterious disorder with its economic and social implications, including time lost from work, play, and costs of medications for its treatment are truly staggering.

Heretofore, suitable agents for headache treatment have been few, and often produce side effects, such as sedation or nausea that in themselves may be temporarily debilitating. It seems clear, then, that the search for pharmacological deliverance from this scourge must continue.

Ethnobotanical study has confirmed the incidence of headache among native peoples worldwide, as well as the many herbal remedies employed by them for its treatment. In the author's preliminary literature surveys, these treatments have often consisted of local application of various leaves or decoctions employed as washes. In contradistinction, internal treatment with botanical agents among indigenous peoples of French Guyana (Lescure et al., 1987), West Africa (Ayensu, 1978), and Australia (Isaacs, 1987), has been comparatively rare. However, in Northwest Amazonia, a region of tremendous biodiversity, several tribal peoples have developed a varied pharmacopoeia which includes many agents taken internally for headache treatment. The focus of the present study is the review and analysis of the literature pertaining to these tribes, their concepts of disease, and the rank-ordering of the agents they employ for headache treatment. An attempt was made to pool previously published materials from diverse sources into a new form that may be more accessible to interested researchers, whether they be ethnobotanists, biochemists, medical anthropologists or neurologists.

Study Area

The geography of the area centers around Ecuadorian Amazonia in its (disputed) border region with Peru and Colombia. Five tribal groups inhabit this area, including the Kofan, Siona-Secoya, Waorani, Shuar and lowland Quichua, all with varying degrees of intertribal contact and commerce. This region is variously classified as tropical rain forest, tropical lowland rain forest, or tropical wet forest and includes regions westward into the Andean foothills (Fig. 1).

The habitat in question is at risk due to encroachment by settlement and industrial expansion. The discovery of oil in this area has added the possibility of pollution by petroleum by-products to the growing list of threats the region faces. Even more distressing from an ethnobotanical standpoint is the fact that these tribes are becoming rapidly acculturated, despite the fact that for nearly five hundred years contact with "Western society" was quite limited. Since increasingly fewer tribal people are pursuing aboriginal lifestyles, it is quite likely that the pharmacognostic knowledge of the ages may be lost within a generation.


Disease Concepts: Medical Anthropology of the Tribes

Of these groups, the lowland Quichua tribe (also known as Canelo, Quechua, Ketchwa) has undergone some integration since Spanish colonial times. This group is part of a much more widely spread tribe descended from ancient Incan peoples with an empire that extended through the Andean region. Amongst the lowland Quichua, illness is perceived not just as a physical affliction but rather a disturbance of a more basic "body-spirit harmony", the therapy of which often requires a specialist. Nonetheless, treatment of a given disorder often begins in the home. Failing resolution, consultation would be sought through the experience of "personas mayores" ("older people") who then prescribe herbal preparations and directions in the way of food taboos and additional rules that the sick person should observe. In this manner, the treatment of illness is integrated with other aspects of social, ideologic and economic factors of life. It is said that much of the pharmacopoeia is common knowledge among the populace (Iglesias, 1987).

To the south, in an overlapping territory, lies the region of the Shuar, previously known as the Jivaro (Fig. 1). Early contact with this tribe was quite limited due to their fearsome reputation as head-hunters. Their approaches to disease treatment are distinctive. A person who is ill will often solicit cures through a type of shaman referred to as a "pener uwisin" who is a valued member of the community in his role in assuring the welfare of his neighbors. It is necessary for tribesmen to curry favor with the shaman to assure future cures. Healing is then supplied as a method of procuring valuables. In the past, one healing treatment might represent the barter equivalent of a shotgun. Shamans have been said to have a hierarchical relationship; apprentices providing gifts in payment and exchange for instruction and magical power. This power is in the form of "spirit servants" called "tsentsak", or magical darts which are invisible in normal levels of consciousness and exist in an infinite variety of forms. Normally, "tsentsak" reside in the body of the shaman. A person may be bewitched by the shaman, sending his "tsentsak" into the body of a victim. In contrast, cures are effected by entreaties to the "tsentsak" to "suck the intruding magical dart out of the patient's body" (Harner, 1971).

Interestingly, the most powerful and sought after darts are attributed to the lowland Quichua shamans to the north. In turn, the Shuar consider white man's "tsentsak" to be yet again superior. At the time of Harner's study, it was his impression that one in four adult men was a shaman and this vocation was rare among women.

Pathophysiologically, Shuar have believed that witchcraft is the cause of the vast majority of diseases while "senura" or "white men's diseases" are confined to illnesses of an epidemic nature. Traditionally, the normal waking state has been considered by the Shuar to be an illusion. In contrast, the true forces underlying daily life are felt to be supernatural and require hallucinogens for viewing and manipulation. It is said that bewitching and curing shamans both employ hallucinogens, preferably Banisteriopsis species (Malpighiaceae), or in some cases the stronger Brugmansia arborea (L.) Lagerheim (Syn.Datura arborea L.) (Solanaceae). Shamans employ the hallucinogenic "natema" drink to direct their "tsentsak", and the latter become perceptible while under the influence. It is felt that laymen can treat white man's diseases with herbs, but Harner reported that shamans did not employ them. It was his feeling that herbal remedies were little developed in this society, but more recent information may tend to refute this, as will be evident in the Results section of this study.


To the northeast of the Shuar territory, lies the territory of the Siona and Secoya tribes that speak closely related dialects of Tukanoan. They are said to be culturally similar and live in common settlements (Vickers and Plowman, 1984). In addition, cultural contact and intermarriage with the neighboring Kofan have occurred for centuries. Vickers estimates that the surrounding region of the Amazon basin in Ecuador at one time contained twenty-six distinctive native cultural groups but, as of 1984, there were perhaps fifty thousand Indians remaining in seven surviving groups. Whereas the Siona-Secoya had an estimated population of sixteen thousand at the time of the conquest, in the 1980's, this population was reduced to no more than one thousand in the entire region.

As among the Shuar, Banisteriopsis (Malpighiaceae) is at the basis of many important rituals and is "viewed as the medium through which supernatural knowledge and power are achieved" (Vickers and Plowman, 1984). The Siona-Secoya share many herbal remedies with their neighbors the Kofan, and in some instances the names used are synonymous. The Secoya in particular are recognized as powerful healers, and it is said that the Quichua bring their own people up to two days distance by canoe to be treated (King, 1991).

Vickers has observed that headache is a relatively less frequent complaint among the Siona (Vickers, personal communication, 1991). Apparently, at least among males, affliction by headache or epistaxis, particularly during "yaje" ceremonies is often attributed to ritual contamination by women, who are therefore segregated during their menses.

The neighboring Kofan (Cofan) were first studied ethnobotanically by Pinkley in 1965, at which time they had an estimated population of less than five hundred (Pinkley, 1973). The tribe was quite isolated but rapid changes were operative due to local petroleum exploration. It had been felt that they were less acculturated than their co-tribesmen across the Colombian border. Pinkley observed that among the Kofan health and disease were dependent on spirits which could be good or evil. He observes that "...since plants can cause sickness and death, they believe also in the corollary, plants can provide health and life...". They employ various "sehe pa", their term used generically for medicines or arrow poisons which bring death to an evil spirit. Pinkley found the knowledge of medicinal botanicals was widespread in the tribe, but they also believed in the unique medicinal abilities of shamans who were consulted when initial herbal treatments failed. The shaman correspondingly would seek knowledge from the spirit world through "yaje", the "leaf that forecasts the future". The latter is a hallucinogen usually formulated from Brugmansia (Solanaceae) or Brunfelsia (Solanaceae). Interestingly, at the time of his writing, only three agents were observed for headache treatment by the tribe:

Trichomanes membranaceum L. (Hymenophyllaceae), a Heisteria species (Olacaceae), and an unidentified agent, "tsampi tsitisindi sehe pa". All of these agents were used externally. However, subsequent study demonstrates that the Kofan's armamentarium for treatment of headache turned out to be significantly broader and includes several agents employed internally (vide infra).

The most isolated of the tribes would certainly be the Waorani (or Huaorani), previously known as "Auca", a Quichua term meaning "savage". The Waorani may have existed in isolation due to their disregard for outsiders who are labelled "cowode" or "non-human". The Waorani have demonstrated a xenophobia that may have been their salvation over the centuries, since early contact with this tribe often resulted in the demise of the interlopers. In 1981, their population was estimated at six hundred-sixty, scattered over a widespread area primarily between the Napo and Curaray rivers (Davis and Yost, 1983). This tribe seems to be linguistically distinct from all others in the region. One measure of their isolation would be indicated by the fact that the common cold was unknown to this tribe prior to contact with Westerners. They represent a group of hunter-horticulturists who have been somewhat unique due to their hydrophobic tendencies, thus avoiding major rivers.

It was found that the Waorani had no specific classification of disease, but rather would tend to treat symptoms through a principle of association or "sympathetic magic" (Davis and Yost, 1983). They felt the characteristics of one entity or object may pass to another, and, hence, plants with a strong odor might repel symptoms in a manner reminiscent of the "doctrine of signatures". The Waorani have recognized two types of affliction. The first is "ononqui" which are diseases arising for no particular reason. "Ononqui" may be treated by any adult who employs a suitable plant remedy. If no response is forthcoming, treatment by a shaman or "ido" is then sought.

The second type of diseases are "wenae" which are caused by spirits sent by another shaman to try to kill the victim. "Wenae" may only be treated by a shaman. Any persistent or severe illness is seen as "wenae-induced". In contrast to the other tribes in the area, the pharmacopoeia of the Waorani has been quite limited. However, it has the distinction of having arisen solely by a process of scientific experimentation without influence by outsiders. The use of herbal agents has obviously been affected by tribal attitudes. It was observed that "...Since the Waorani tend to allow illness to progress to a state which makes them dysfunctional before they attempt to halt its progress, many minor pains, fevers, or irritants go undiagnosed and untreated" (Larrick et al., 1979). This attitude seems to be mirrored in regard to headache, which is usually not specifically treated unless the victim fortuitously comes across a suitable plant remedy. Rather, the headache sufferer would tend to stoically rest and attempt to allow the symptoms to pass (Dr. James Yost, personal communication, 1991).

It was the feeling of Larrick and his colleagues that many of the Waorani's herbal remedies did in fact have the desired effect and their innate value was strongly believed by the populace. They observed that "...The Waorani had complete faith in their system because of its integration with their cosmology..." (Larrick et al., 1979).

Methodology

Various available standard references were employed as a point of departure for this research. Additionally, computer searches of the medical literature, and the BIOSIS and NAPRALERT databases were undertaken. The author attempted to be as comprehensive as possible, but realizes such a goal is fleeting.

In order to produce an Ethnobotanical Rating Scale, a grading system has been applied to each plant based on its patterns of use and degree of study. This evaluation necessitates certain assumptions of questionable validity, one being that agents which are used internally are more likely to contain efficacious ingredients. With the advent of cutaneous delivery system for drug administration (e.g. transdermal application of scopolamine, estrogen, et al.), the possible bioactivity of poultices, washes, etc., cannot necessarily be dismissed (e.g., Brugmansia arborea (L.) Lagerheim). It is the author's impression that new discoveries are more likely among plants that are as yet uninvestigated chemically. Hence, an additional point on the scale accrues to the unstudied species.


The following grading scale was used:

* 1 point for 2 or more independent sources citing use for headache.
* 1 point for each Ecuadorian tribe employing plant
for headache* 1 point for absence of previous chemical investigation
* 5 points for internal use of agent in headache treatment.

The tallied points were ranked as follows:

Points Ranking

8-9 Most Promising
6-7 Promising
4-5 Possible
0-3 Unlikely



Results

Plants employed for headache treatment by Ecuadorian Amazon tribes are listed below alphabetically by plant family, then by genus and species. A brief description of each species, including available information on pharmacologically relevant chemical data, along with local names and ethnobotanical uses, is given. Scores and rating scales based on the criteria explained in the Methodology are indicated at the end of each species description.

ECUADORIAN AMAZONIAN PLANTS EMPLOYED FOR HEADACHE TREATMENT



ACANTHACEAE

Fittonia_albivenis (Lindl. ex Veitch) Brummitt
Kofan: "minakoro", "ne-na-koo-roo"
Quichua: "misapu-panga"

This is a primary forest low-growing creeping herb, as well as ruderal, that has red veins before drying, with inconspicuous flowers. It was collected as an unplanted herb in a garden in Shushufindi (Vickers and Plowman, 1984). Its distribution ranges from Ecuador to Peru, Colombia, Bolivia,and Northern Brazil. No record indicates that the species nor its genus have been chemically studied.

Among the Kofan, a leaf tea is employed in cases of urinary pain or difficulty (Schultes and Raffauff, 1990).

The Siona-Secoya use a decoction of the bruised and boiled plant to relieve headache or muscle pains; it can be ingested or rubbed on the affected area (Vickers and Plowman, 1984).

Score: 9 points
Rating: Most Promising


AMARANTHACEAE

Cyathula achyranthoides (HBK) Moquin
Quichua: "allcupanga"
Shuar: "yajauch isma"
Western Ecuador: "cadillo piche de gato"

This is a common "weedy herb" up to 1.5 m in height, with narrow leaves 5-12 cm long, a spicate inflorescence at least 15 cm long, and fruits 5 mm long that catch on clothing. It is found at forest edges (Dodson and Gentry, 1978). This plant is widely distributed from the Carribean and Mexico to Brazil. The family contains saponins and proto-alkaloids (Schultes and Raffauf, 1990), but no biological activity or biochemistry data have been reported.

Among the Quichua, the flowers and shredded leaves are applied to dog bites (Lescure et al., 1987). The Shuar employ it by collecting raw young leaves that are eaten to relieve headaches. It is also used against fever (Dr. Bradley Bennett, personal communication, 1991).

Score: 7 points
Rating: Promising



AQUIFOLIACEAE

Ilex_guayusa Loesener
Quichua: "huayusa-panga"
Shuar: "wayus", "wais"
Spanish: "hojas de guayusa"

A tree cultivated by many tribes (illustrated on pp. 80-81, Schultes and Raffauf, 1990). It is known to contain caffeine and is related to mate of Peru. Used commonly as a stimulant drink, "guayusa", but also as a tonic, calmative, stomachic, to "kill the bitter taste" of ayahuasca and "prevent hangover" (Schultes and Raffauf, 1990). The Quichua use this species for headache and body pains. A few leaves are infused in a little water and 1/2 cup is drunk. Excess produces vomiting (Iglesias, 1987).

The Shuar brew a leaf tea that is used to treat headache, stomachache, pain and dizziness. It is also added to Banisteriopsis preparations (Dr. Bradley Bennett, personal communication, 1991).

Score: 8 points
Rating: Most Promising
(The possibility exists that the therapeutic effects for headache may be related to the caffeine content.)


ARACEAE

Anthurium c.f.uleanum Engler Kofan: "karico"

A common epiphytic herb in the primary forest, whose minute flowers are borne on a large spike, often covered by a spathe. It was collected in Shushufindi (Vickers and Plowman, 1984). Its range includes Ecuador, Peru and Brazil. A member of this genus contains glycosides and saponins (Der Marderosian et al., 1979), but no records indicate that this species has been chemically studied.

The Secoya grind the roots with a rock and and then put it to boil. The
decoction is ingested for headache (Vickers and Plowman, 1984).

Score: 8 points
Rating: Most Promising


Anthurium_sp.(Sect._Pachyneurium)
Kofan: "shushufindi kari"
Secoya: "kaho"

This is an epiphytic herb on tree trunks in the primary forest, that was collected in Shushufindi (Vickers and Plowman,1984). The Secoya crush the roots and mix it with water. The infusion is imbibed as a remedy for headache (Vickers and Plowman, 1984).

Score: 8 points
Rating: Most Promising


ASTERACEAE

Eupatorium_macrophyllum L. Shuar: "tui tui"

Members of this genus are known to contain a variety of alkaloids (Grenand et al., 1987). Various terpene derivatives have been isolated from this plant (Warning et al., 1987), but no studies of biological activity have been published. The Shuar aspirate(?) the leaves to relieve headache(Lescure et al., 1987).

Score: 6 points
Rating: Promising



BIGNONIACEAE

Pachyptera_species
Quichua: "sachaajo", "sacha ajo"
No chemical data appear to have been reported in the literature. Among the Quichua, a compress of the leaves is placed on the forehead to relieve headaches and fevers (Lescure et al., 1987).

Score: 2 points
Rating: Unlikely



COMMELINACEAE

Commelina diffusa N.L. Burman
Shuar: "sanchu"
Spanish: "suelda con suelda"

This is a prostrate herb with blue petals, of 30 cm height, that is locally common in second growth vegetation at Rio Palenque (Dodson and Gentry, 1978). Its range is pantropical. A related species is said to contain alkaloids (Schultes and Raffauf,1990), but no reports of chemical analysis were found for this species.

Among the Shuar, a tea is made from the flowers and is employed
as an emolient. It is used internally to treat headache by consuming 250 ml
before breakfast or bed (Dr. Bradley Bennett, personal communication, 1991).

Score: 7 points
Rating: Promising


ERYTHROXYLACEAE

Erythroxylum ulei O.E. Schulz
Kofan: "awi-iti-fasi", "iti-fasi"
Rio Eno Siona: "suara-iko"
Shushufindi Siona: "na-nyame-iko"

This is a shrub related to the more familiar Erythroxylum coca, but its corolla is yellowish white, whose distribution covers tropical Andean forests. It contains flavonoids, but questionably no alkaloids (Schultes and Raffauf, 1990). However, tropacocaine was recovered in one study from Peru (El-Imam et al., 1985). It was collected from cultivated plants in gardens in Shushufindi and Rio Eno (Vickers and Plowman, 1984), as well as in Mendez Bella Union according to a record at the Botanical Museum, Harvard University.

The Kofan crush the leaves, boil them with water and drink the decoction (cold water infusion may also work) for itching, sore throat, stomachache, bloody diarrhea and amebiasis. A decoction of macerated leaves is taken for headache (Vickers and Plowman, 1987).

The Rio Eno Siona use this species similarly for sore throat and
stomachache (Vickers and Plowman, 1987), while the Shushufindi Siona use it for similar indications including headache (Vickers and Plowman, 1987).

Score: 7 points
Rating: Promising



GESNERIACEAE

Codonanthopsis_dissimulata (H.E. Moore) Wiehler
Kofan: "kugi-kisi", "hugi kisi".
Siona: "huku-iko", "kuku i ko"

This is an epiphytic herb with fleshy leaves that forms "ant gardens" on trunks of trees in the margins of forests and Mauritia flexuosa swamps. It was collected in Shushufindi (Vickers and Plowman, 1984). Its range covers northern South America. No chemical data on this species or genus are found in the literature.

The Kofan use the leaves pounded with a rock and boiled for headache by snorting the liquid with a spoon. For toothache, it is used as an oral irrigation (Schultes and Raffauff, 1990). The Siona use it similarly for headache and toothache (Vickers and Plowman, 1984), and for ant stings (Schultes and Raffauff, 1990).

Score: 8 points
Rating: Most Promising


GRAMINEAE

Cymbopogon citratus (DC) Stapf
Ecuador: "hierba luisa", (?lemon verbena or ?Aloysia)
English: "lemon grass"
Quichua: "hierba luisa".
Siona: "gati-ma-nya"

This is a tropical Asian species with fragrant leaves containing essential oils, largely terpenoid. It forms a perennial grass up to 70 cm in height, in low hummocks. The leaves are linear, 50-70 cm long, 1.5-2 cm wide, and glaucous-green in color. Flowers are rarely produced (Dodson and Gentry, 1978).

In Ecuador the plant is cultivated, and recommended as a drink to allay abdominal pain, rheumatism and ulcers (Lescure et al., 1987).

The Quichua utilize it for headache and stomach pain by infusing several leaves in a large amount of water, and drinking one cup as necessary. The root is also employed by grating it to make an infusion, of which 1/2 cup is drunk (Iglesias, 1987).

Among the Siona, the leaf infusion with sugar is used for stomachache (Vickers and Plowman, 1984).

Score: 6 points
Rating: Promising



Paspalum_conjugatum Berg.
Shuar: Vernacular term not translatable (Lescure et al., 1987) Siona:
"sarataya"
Western Ecuador: "turvara"

This is a weedy stoloniferous grass up to 50 cm tall, with linear leaves 3-10 cm long and 0.6-1 cm wide, whose inflorescence consists of opposite drooping, yellow-green, 4-10 cm racemes with 1 mm sessile spikelets (Dodson and Gentry, 1978). It is found in house yards and disturbed areas, and was also collected in Shushufindi (Vickers and Plowman, 1984). Its distribution includes the tropical Americas, and Eastern Hemisphere. It is said to contain cyanogenetic heterosides (Grenand et al., 1987). Dr. James A. Duke (personal communication, 1991) raises the very valid point and intriguing question that the ethnobotanical efficacy of this and other grasses in headache treatment may be due to an ergot-like fungus infestation, akin to that of rye grain by Claviceps purpurea.

The Shuar prepare an infusion of this plant utilized to relieve headaches (Lescure et al., 1987).

Score: 6 points
Rating: Promising


HYMENOPHYLLACEAE

Trichomanes_membranaceum Linnaeus
Kofan: "tusana-si-sehe-pa"

This vine-like species is an epiphyte with an elongate rhizomal stem. Its leaves are deeply and irregularly lobed, about 3 cm long and broad, with dichotamous veins, and sporangia at their margins. It is found on tree trunks up to 2 m above the ground (Dodson and Gentry, 1978). Its range covers the Carribean, and Mexico to Bolivia. C-glycosylxanthones have been identified in other species of this family (Schultes and Raffauff, 1990).

Among the Kofan, the plant is boiled and the head is bathed in the liquid to treat headache (Pinkley, 1973).

Score: 1 point
Rating: Unlikely


LEGUMINOSAE

Cassia macrophylla Kunth
Kofan: "kongee-hee-te-ta"

No studies of biological activity or biochemical analysis appear to have been carried out for this species. The Kofan employ a wash prepared from this plant to treat headache and earache (Schultes and Raffauff, 1990).

Score: 2 points
Rating: Unlikely


Cassia_ruiziana Vogel
Kofan: "konghi-hi-se-he-pa"

No studies of biological activity or biochemical analysis appear to have been performed on this species. The Kofan scrape the bark of branches to produce a wash for
headache and earache (Schultes and Raffauff, 1990).

Score: 2 points
Rating: Unlikely


Myroxylon_balsamum Harms
Quichua: "balsamo-cara"
Spanish: "corteza de balsamo"

This is one of several closely related species of evergreen trees yielding vanilla-scented resins, widely used in Peru for skin sores, as a febrifuge, antiparasitic, expectorant or stimulant (Ramirez et al., 1988). It contains sesquiterpenes (Friedel and Matusch, 1987) and flavonoids (De Oliveira et al., 1978).

The Quichua extract the bark and scrape off its interior, mix it with a little lukewarm water and drink it in its entirety, to treat headache. Generally, one or two doses are sufficient. If pain persists, it is said to be preferable to treat it with a "stronger" preparation, such as "nigri-panga", an unidentified vine (Iglesias,1987).

Score: 6 points
Rating: Promising


MELIACEAE

Melia_azedarach L.
Quichua: "copapanga", "cupal panga"

This is a tree that grows 10-15 m in height with 30-100 cm leaves and toothed leaflets. It is sold by nurseries in the U.S. as "Chinaberry" (Sunset, 1988). The genus is known to contain azaridine, margosine, and paraisine (Raffauf, 1970), while the leaves of this species contain coumarins and lignans (Khalil et al., 1979), as well as flavonoids (Marco et al., 1986). An anti-inflammatory activity has been reported in 1 of 3 albumin stabilizing assays (Han et al., 1972).

Among the Quichua, the cooked leaves are eaten to relieve headaches (Lescure et al., 1987).

Score: 6 points
Rating: Promising


MENISPERMACEAE

Abuta grandifolia (Mart.) Sandwith
Kofan: "titicocho tsatiko"
Quichua: "caupanga"
"montelomuyo"
"yahuaticaspi"
"yahuatipanga"
Secoya: "dayawi uo"
Siona: "ancabesux"

This vine whose range includes the Amazon Basin was originally collected in Shushufindi (Vickers and Plowman, 1984). It has been chemically studied and shown to contain the alkaloids palmatine and derivatives of berberine. Palmatine has a strong antipyretic action as well as a depressant effect on the blood pressure and the central nervous system (Grenand et al., 1987).

In Ecuador it is used in labor for hemorrhage and pain, and has been employed to treat colic in nervous children; according to Schultes, one treatment lasts for one year (Schultes and Raffauff, 1990).

The Quichua make a compress of the leaf decoction and use it to treat headache. A decoction of the leaves mixed with the bark of "piton" is drunk by women before giving birth to speed the recovery of their their strength (Lescure et al., 1987). It is also used to treat snakebite (Schultes and Raffauff, 1990).

Among the Siona, a leaf infusion is used as a febrifuge, and also as an
ingredient of curare (Schultes and Raffauff, 1990).

Score: 1 point
Rating: Unlikely



MONIMIACEAE

Siparuna sp.
Ecuador: "jatun-malagre-panga"
Quichua: "huairamanalli"
"huaripanga"
"malagre"
"nuanapechanapanga"
"raposapanga"
Waorani: "nonangonca"

This is a forest shrub which is used to treat "bad wind" or "bad air" by fanning the patient with a fistful of stems with leaves (Lescure et al., 1987).

Among the Quichua, "huairapanga" is used to treat herpes by applying the heated bark to infected areas, while the aromatic leaves of the "malagre" are rubbed on the forehead and strongly aspirated to treat headache. The red fruit is crushed with the leaves and placed on the forehead to treat fever and headaches (Lescure et al., 1987).

The Waorani crush the fruit and leaves to form a pungent mixture that is rubbed on the face and head to treat "fever headache" (Davis and Yost, 1983). An infusion of the leaves is employed as a febrifuge (Lescure et al., 1987).

Score: 8 points
Rating: Promising


OLACACEAE

Heisteria sp.
Kofan: "avi-sehe-pa"

This plant is from a genus of trees and shrubs in which scopalamine was found in one species, but others have been little studied (Schultes and Raffauf, 1990). It was collected in a Kofan village (Pinkley, 1973).

Among the Kofan, a decoction of the leaves is used as a wash or compress
for headache and for epistaxis (nosebleed). The leaves are also steeped in cold water and the infusion used to bathe the head (Pinkley, 1973).

Score: 2 points
Rating: Unlikely


PALMAE

Jessenia bataua (Mart.) Burret
Colombia: "milpesos", "seje" Quichua: "ungurahua"
"shimbi muyo"
Shuar: "cun-cu-ki"
Siona: "gosa", "cosa"
Spanish: "chapil", "chambil" "ungurahui"
Waorani: "pe-towe" - tree
"pe-to-mo" - fruit
"pe-to-ba" - leaves
"pe-to-coo" - leaf base
"peto" - adventitious roots
"petowe"- mature tree

This is a common palm tree of the primary forest, which was collected in Shushufindi (Vickers and Plowman,1984). Its range includes the Amazon and Orinoco basins.

The Siona extract oil from the mesocarp which is used in cooking and as a
hair tonic (Lescure et al., 1987). Among the Waorani,"peto" (the adventitious root) is used for headache, stomachache, to mitigate diarrhea, and as a vermifuge (Davis and
Yost, 1983).

Score: 6 points
Rating: Promising

SOLANACEAE

Brugmansia_arborea (L.) Lagerheim
(Syn. Datura arborea L.)
Quichua: "huanduc", "lumucha guantu"
Spanish: "floripondio".

This is one of a few related species of small trees commonly employed as hallucinogens (illustrations pp. 419-423, Schultes and Raffauf, 1990). It is found as a cultivated plant.

The Quichua make longitudinal cuts in the stems and branches and apply them to the head or other painful body part. The strip is bandaged in place for 15 minutes. If employed longer, a soporific or temporary anesthetic effect may be produced(Iglesias, 1987). A preparation of this plant is also given to dogs to make them better hunters (Lescure et al., 1987).

Score: 6 points
Rating: Promising


VERBENACEAE

Lantana armata Schauer
Shuar: "muras"

This plant belongs to a genus of shrubs and herbs, often prickly, which contains alkaloids, camphor, etc. (Schultes and Raffauf, 1990). No reports of biological activity or biochemical analysis have been found for this species.

Among the Shuar, the cooked leaves are eaten to relieve headache, as well as for general body pains (Lescure et al., 1987).

Score: 7 points
Rating: Promising


ZINGIBERACEAE

Zingiber_officinale Roscoe
Colombia: "ajijilla"
Ecuador: "ajilla", "jenjibre"
Kofan: "afifindi", "chapepnomen ba"
Quichua: "ajirinrin"
Secoya: "pia nuni", "pia di udi"
Shuar: "tertuyagas"

This species is an introduced cultivated rhizomatous herb, native to tropical Asia, which has been shown to exert prostaglandin-like inhibition and depressant effects (Schultes and Raffauf, 1990). It has also been documented to show clinical efficacy against migraine (Mustafa and Srivasta,1990).


The Kofan, Quichua, Secoya, and Shuar reportedly employ a decoction of the rhizome to relieve stomachache and diarrhea. The Shuar, additionally, apply a beaten egg with the plant on hematomas (Lescure et al., 1987).

Among "Spanish" peoples in the study area, crushed leaves are made into a compress to relieve pain, while the macerated rhizome is employed to relieve headaches and stomach pain. When one's eyes exhibit excrescence, a drop of sap is applied once; excessive use is said to burn the eye (Lescure, 1987).

Score: 5 points
Rating: Possible
Discussion and Conclusions

It has been estimated that 3.5 to 4 billion of the world's population rely on plants as their primary source of drug therapy (Farnsworth and Soejarto, 1985; Farnsworth, 1988). Additionally, it has been estimated that of the 250,000 known species of flowering plants on earth, current plant-derived official drugs are obtained from only approximately ninety-five species. Inasmuch as current estimates for remaining undiscovered plant species may vastly expand the total, it is easy to understand that a great untapped reservoir of pharmacological agents is possible.

Current interest in taxol, derived from the western yew, Taxus brevifolia Nutt. (Taxaceae), illustrates some important points. This species has been scorned previously by foresters due to lack of profitable industrial application. At present, its numbers have dwindled and demand outstrips the supply. Because taxol is currently extremely difficult to synthesize in the laboratory, a sustainable yield from harvested yew trees has become a clear priority, as has been widely publicized in the lay press.

A very similar scenario is possible for countless rain forest plants. The two dozen species discussed in this study as potential headache remedies may well offer promise. In addition to the plants listed herein, the Kofan employ one unidentified agent for headache treatment (Pinkley, 1973), whereas the Lowland Quichua have seven, as well as three compounded formulations (Iglesias, 1987).

Modern herbals (Kowalchik and Hylton, 1987) offer similar numbers for botanical agents useful for headache, but these represent the pooled knowledge of European and American herbalists over the last few hundred years. In contrast, the Ecuadorian Amazonian tribes never numbered more than several thousand individuals in an area roughly equivalent to that of the state of Maine. That there are so many headache cures employed by the tribe may indicate to some that no one agent could be very impressive in its clinical value. However, contemplation of the analogous Western pharmacopeia with its plethora of over-the-counter remedies, as well as prescription drugs for symptomatic and prophylactic treatment might provoke a similar criticism and skepticism. Apparently, far more research is necessary in the area. The author proposes in subsequent studies to pursue field investigation of these plants, and to explore their clinical use by the native peoples of Ecuador. The rank-ordering of the species based on criteria explained in this paper will be a useful guide for this purpose (Table 1).


TABLE 1
PLANT RANKING LIST

Plant Score Potential *
Fittonia albivenis 9 Most Promising
Anthurium c.f. uleanum 8
Anthurium sp. 8
(Sect. Pachyneurium)
Codananthopsis dissimulata 8
Ilex guayusa 8
Siparuna sp. 8
Commelina diffusa 7 Promising
Cyathula achyranthoides 7

Erythroxylum ulei 7
Lantana armata 7
Brugmansia arborea 6
Cymbopogon citratus 6
Eupatorium macrophyllum 6
Jessenia bataua 6
Melia azedarach 6
Myroxylon balsamum 6
Paspalum conjugatum 6
Zingiber officinale 5 Possible


Cassia macrophylla 2 Unlikely
Cassia ruiziana 2
Heisteria sp. 2
Pachyptera sp. 2
Abuta grandifolia 1
Trichomanes membranaceum 1


* See Methodology, for criteria used as basis to assign points.


The plants discussed in this study have been identified and classified botanically in most cases. Few, however, have been investigated chemically, and none for neuropharmacological activity in a manner that might adequately predict clinical efficacy, as will be outlined subsequently.

The conversion of ethnobotanical information into practical suggestions for subsequent drug research has always been problematical. This has been particularly true for headache research, compounded by the fact that no animal model for clinical headaches exists, not even among the primates.

Modern advances in neuropharmacology may offer the key to new methods of biochemical screening that could provide a rapid, and likely clinically valid, approach to future assessment of these and other botanical agents for headache treatment. Current headache theory has led to research focusing on serotonin receptor subtypes as key factors in the treatment of headache (see Appendix 1)(Humphrey, 1990; Peroutka, 1990). Pharmaceutical agents that are efficacious in the symptomatic treatment of migraine tend to display strong agonistic activity on serotonin type 1D receptors (e.g., dihydroergotamine, sumatriptan), whereas, agents of benefit in migraine prophylaxis, for the most part, demonstrate marked antagonistic activity on serotonin type 2 receptors (e.g., amitriptyline, cyproheptadine). Finally, antagonistic activity on serotonin type 3 receptors indicates efficacy in combatting nausea (e.g., ondansetron) (Peroutka, 1990). In this manner, laboratory analysis for plant components that may be clinically efficacious in headache treatment has become increasingly possible and may serve to
mitigate the lack of a working animal model for headache.

To date, no studies have been published that focus on the serotonin receptor activity of any plants employed ethnobotanically for headaches. For example, agents such as the Ecuadorian species discussed in this study, especially those demonstating greater promise on clinical grounds, might be rapidly screened for agonistic activity on serotonin type 1D receptors. This search should be expanded to include putative candidates from other cultures, such as dwarf buckwheat, Eriogonum ovalifolium Nutt.
(Polygonaceae), a headache remedy of native peoples of North America (Parker, 1984; Parker and Parker, 1986). Similarly, agents such as feverfew, Tanacetum parthenium (L.) Bernh. (Asteraceae), that are purported to be of prophylactic value in headache management (Johnson et al., 1985), and its supposed active ingredient, parthenolide, could be examined for antagonistic activity on serotonin type 2 receptors. Finally, the search could be broadened further to include screening of arthropod and marine organisms, both flora and fauna, as a method of "chemical prospecting".

Should the search for efficacious headache remedies from Amazonia prove successful, the potential exists for further cultivation and collection of the plants in Ecuador, which could possibly provide a cash crop for an economy requiring additional diversification. Economic stimulation could lead to preservation of the rain forest's existing biological diversity through techniques of "extractivism", as opposed to traditional slash and burn clearing or the pursuit of monocultural techniques on a large scale.

One of the profound wonders of nature is that "plant defense compounds" have biochemical activity on the mind of man. If discovery of new therapeutic agents for headache treatment contributes to the preservation of vestiges of the rainforest, then mutual compatability between scientific investigation and conservation would be achieved.

Acknowledgements

I owe thanks to many individuals. First of all, to Dr. R.E. Schultes, for his pioneering work in the field, his inspiration, support, countless suggestions and the generous gift of his time. To Dr. James Castner, who made many useful suggestions. To Dr. Keith Parker, whose work with chemical analysis of Native American botanicals used for headache treatment demonstrated to me that I had a soul-mate for this type of work in Montana, and for his review of the manuscript. To Dr. Patricio Abad Herrera of Quito, Ecuador, whose correspondence and five thousand mile phone calls encouraged the author. To Ms. Lisa Conte and Drs. Steven R. King and Dennis McKenna of Shaman Pharmaceuticals, for their continued encouragement and many suggestions. To Dr. Jim Duke of the U.S. Department of Agriculture, for his review of the manuscript, and his demonstration to the author of the mutual compatibility of ethnobotany and bluegrass music. To Mr. Tod Gregoire, former Western Montana Clinic librarian and a master of the computer search, whose hours of enthusiastic work tracking obscure sources was critical to this research. To Lynda Roberts and Aleta Windes, for their endless stenographic services, meeting the challenge of multiple esoteric languages even more difficult than medicine. To Bettina Escudero, Peggy Loughren, and Nydia Vargas of "It's Spanish Time" in Missoula, for their wonderful Spanish instruction and help with translation. To the staff of ORSTOM in Quito, for generously sending their book, which proved to be a critical research source. To the late Dr. Howard Robbins for his good counsel and humor: may he yet know peace. To Don Montague of the South American Explorers Club in Denver, for his assistance and access to books. To Kathy Coward and Wendy Lehman for their patience and triage work, and most of all, for not laughing at me while reading microfilm with an ophthalmoscope. And, ultimately, to Kay Frey for her patience and forbearance in understanding the unusual form of her husband's midlife obsession.

This study was personally funded.


References

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APPENDIX 1

Ethan B. Russo, M.D.


ATTRIBUTES OF AN IDEAL DRUG FOR HEADACHE


Based on present knowledge of migraine neurotransmitter pharmacology (Peroutka, 1990), this author believes that the following attributes are "ideal" for drugs to treat headache:

1) Symptomatic treatment
High affinity and specificity for agonistic activity on serotonin type 1D receptors to abort headache. Also desirable, an antagonistic activity on serotonin type 3 receptors to combat nausea (Peroutka, 1990).

2) Prophylactic treatment

Antagonistic activity on serotonin type 2 receptors (Peroutka, 1990)

3) A lack of activity on other neurotransmitter receptors (e.g.
cholinergic or adrenergic) would be desirable, although actions that boost endorphin levels or inhibit substance P activity may be distinctly advantageous.

4) Freedom from undesirable side-effects (e.g. sedation, gastrointestinal upset)

5) Reasonable cost.

INDEX TO NATIVE NAMES AND THEIR SCIENTIFIC EQUIVALENTS
Key:
KO = Kofan, QU = Quichua; SE = Secoya; SH = Shuar; SI = Siona; WA = Waorani


"afifindi" (KO) Zingiber officinale (Zingiberaceae)
"ajirinrin" (QU) Zingiber officinale (Zingiberaceae)
"allcupanga" (SH) Cyathula achyranthoides (Amaranthaceae)
"ancabesux" (SI) Abuta grandifolia (Menispermaceae)
"avi-sehe-pa" (KO) Heisteria sp. (Olacaceae)
"balsamo-cara" (QU) Myroxylon balsamum (Leguminosae)
"caupanga" (QU) Abuta grandifolia (Menispermaceae)
"chapepnomen ba" (KO) Zingiber officinale (Zingiberaceae)
"copapanga" (QU) Melia azedarach (Meliaceae)
"cosa" (SI) Jessenia bataua (Palmae)
"cun-cu-ki" (SH) Jessenia bataua (Palmae)
"cupal panga" (QU) Melia azedarach (Meliaceae)
"dayawi uo" (SE) Abuta grandifolia (Menispermaceae)
"gati-ma-nya" (SI) Cymbopogon citratus (Gramineae)
"hierba luisa" (QU) Cymbopogon citratus (Gramineae)
"gosa" (SI) Jessenia bataua (Palmae)
"huanduc" (QU) Brugmansia arborea (Solanaceae)
"huayusa-panga" (QU) Ilex guayusa (Aquifoliaceae)
"hugi-kisi" (KO) Codonanthopsis dissimulata (Gesneriaceae)
"huku-iko" (SI) Codonanthopsis dissimulata (Gesneriaceae)
"iti-fasi" (KO) Erythroxylum ulei (Erythroxylaceae)
"kaho" (SE) Anthurium (Sect. Pachyneurium) sp. (Araceae)
"kariko" (KO) Anthurium c.f. uleanum (Araceae)
"kongee-hee-te-ta" (KO) Cassia macrophylla (Leguminosae)
"konghi-hi-se-he-pa" (KO) Cassia ruiziana (Leguminosae)
"kugi kisi" (KO) Codonanthopsis dissimulata (Gesneriaceae)
"kuku i ko" (SI) Codonanthopsis dissimulata (Gesneriaceae)
"lumucha guantu" (QU) Brugmansia arborea (Solanaceae)
"malagre" (QU) Siparuna sp. (Monimiaceae)
"minakoro" (KO) Fittonia albivenis (Acanthaceae)
"misapu-panga" (QU) Fittonia albivenis (Acanthaceae)
"muras" (SH) Lantana armata (Verbenaceae)
"na-nyame-iko" (SI) Erythroxylum ulei (Erythroxylaceae)
"ne-na-koo-roo" (KO) Fittonia albivenis (Acanthaceae)
"nonangonca" (WA) Siparuna sp. (Monimiaceae)
"peto" (WA) Jessenia bataua (Palmae)
"pia di udi" (SE) Zingiber officinale (Zingiberaceae)
"pia nuni" (SE) Zingiber officinale (Zingiberaceae)
"sacha ajo" (QU) Pachyptera sp. (Bignoniaceae)
"sachaajo" (QU) Pachyptera sp. (Bignoniaceae)
"sanchu" (SH) Commelina diffusa (Commelinaceae)
"sarataya" (SI) Paspalum conjugatum (Gramineae)
"shimbi muyo" (QU) Jessenia bataua (Palmae)
"shushufindi kari" (KO) Anthurium (Sect. Pachyneurium) sp. (Araceae)
"suara-iko" (SI) Erythroxylum ulei (Erythroxylaceae)
"tertuyagas" (SH) Zingiber officinale (Zingiberaceae)
"titicocho tsatiko" (KO) Abuta grandifolia (Menispermaceae)
"tui tui" (SH) Eupatorium macrophyllum (Asteraceae)
"tusana-si-sehe-pa (KO) Trichomanes membranaceum (Hymenophyllaceae)
"ungurahua" (QU) Jessenia bataua (Palmae)
"wais" (SH) Ilex guayusa (Aquifoliaceae)
"wayus" (SH) Ilex guayusa (Aquifoliaceae)
"yahuatipanga" (QU) Abuta grandifolia (Menispermaceae)
"yajauch isma" (SH) Cyathula achyranthoides (Amaranthaceae)


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