Little Pink Pills: A History of Placebos

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Authors Wagstaff, Jessica

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LITTLE PINK PILLS: A HISTORY OF PLACEBOS

By

JESSICA WAGSTAFF

A Thesis Submitted to The Honors College

In Partial Fulfillment of the Bachelors Degree With Honors in

Physiology

THE UNIVERSITY OF ARIZONA

MAY 2012

~~1 V

Dr. Zoe Cohen Department of Physiology

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Last updated: Nov 15, 2009

Abstract

Why is it that folk remedies have endured the test of time? This review of the placebo effect

begins with definitions of placebo and placebo effect. It delves into the history of the placebo

and the placebo effects, from Cro-Magnon times up through current advances in medicine.

Placebos were present in Ancient Rome and Greece, the Bible, Renaissance Europe. Many

difference substances were used as placebos, including boiled dung, lizard blood, mold and

unicorn hom. Current studies on depression and Parkinson's disease have shown the powerful

responses placebos can produce. Future research is need to unveil the mechanisms and mediators

involved in the placebo effect.

According to Plato, Socrates once said, "[The cure for the headache] was a kind of leaf,

which required to be accompanied by a charm, and if a person would repeat the charm at

the same time that he used the cure, he would be made whole; but that without the charm

the leaf would be of no avail" (Moerman and Wayne, 471).

Socrates was referring to the idea of the placebo effect. The "charm" was most likely a

prayer or a chant, which was thought to "activate" the leaf s healing power. However, does it

exist physiologically? This has been an age-old question regarding the placebo effect.

Observations, studies, and clinical trials tell us yes, the placebo effect does exist. The next

question is, why and how does the placebo effect exist? First, we need to define some terms.

Merriam-Webster dictionary defines placebo as "a usually pharmacologically inert preparation

prescribed more for the mental relief of the patient than for its actual effect on a disorder"

("placebo"). A placebo does not have to be a drug, it can also be surgery or psychotherapy. It can

be inert or active. An active placebo may be an ineffective substance or a substance given at an

insufficient dose. An inert placebo contains no active ingredients, and is often termed a "sugar

pill". A placebo effect, then, can be defined as a response to a placebo, "the nonspecific

psychological or psychophysiological therapeutic effect" (Shapiro and Shapiro, 1-2). There can

be different kinds of placebo effects, positive responses, negative responses or no responses. A

negative effect from a placebo is referred to as a "nocebo" (Moerman, 14). Placebos and placebo

effects have been around for centuries. This paper will delve into the history of the placebo

effect, as well as discuss its significance today and possible research opportunities in the future.

The word "placebo" is a Latin word that translates to "I will please". The word was first

seen in the Hebrew Bible as the word ethaJekh, which was later translated to Latin. In the

thirteenth century, the word placebo appeared in the King James version of the bible, in the

sentence "Placebo Domino in regione vivorum," which means, "I will please the Lord in the land

of the living" In the fourteenth century, the meaning of placebo became secular and took on a

derisive meaning. Placebo was used to describe one who was servile or flattered in order to gain

favors. The word was also understood to mean parasite or "one who servilely echoes another, a

toady." The medical definition of a placebo did not come about until 1803. In Fox's New

Medical Dictionary, a placebo was "an epithet given to any medicine adopted more to please

than to benefit the patient" (Shapiro and Shapiro, 28-29). The idea of the placebo appeared much

earlier in history though.

It is believed by some that the first placebo effect occurred during the Cro-Magnon era,

which dates to approximately 40,000 s.c. Skulls with holes are thought to be the first evidence

of brain surgery, more specifically psychosurgery to relieve mental illness symptoms. This

technique is called trepanning and it involved drilling a 2.5 to 5 cm diameter hole into the skulL

The patients were alive and awake because there was no anesthesia, and the procedure was 30 to

60 minutes in length. Evidence of trepanning has been found in all parts of the world, in Egypt,

Greece, Rome, the Middle East, China, Brazil and North America. There are several theories that

may explain the reason for trepanning. One thOUght is that the surgery was done to free "bad

spirits" from the body, another was that it used to cure diseases, which are now thought to have

been epilepsy and blindness. Trepanning was used up until the 18th century, when it was used as

a technique for bloodletting, which rid of body of "bad fluids" (Sabbatini). It is also thought that

as early as 20,000 s.c., psychological placeboes were used. Most likely, these were some kind

of patient-physician relationships, which played a role in healing because there is no evidence of

substances or medications (Shapiro and Shapiro, 3, Jospe, 1). A Sumerian medical tablet made of

baked clay from 2100 B.C. was found to contain fifteen remedies, which today are viewed as

placebos. Some substances are mentioned, most of which are vegetable based. Wines, lotions,

plasters and fumigations are also mentioned as ways of application of medicine to cure problems

like boils and gastric pains. During Babylonian and Assyrian times, to remedy someone's head

sores, boiled dung was used as well as shaving the person's head until the patient bled (Shapiro

and Shapiro, 3).

The Egyptian Ebers Papyrus from 1500 B.c. is a written document that contains 842

prescriptions and details 700 substances made from different vegetables, animals and minerals,

very few of which had true medicinal value. The Ebers Papyrus discussed how to remedy the

bowels, evacuate the belly, cure a headache and help the bowel movements in a constipated

child. Some of the more serious diseases that plagued the Egyptians were smallpox, dysentery,

typhoid, leprosy, tuberculosis, pneumonia and arthritis (Dollinger). Some medicinal materials

included dirt, lizard blood, hippopotamus fat, grated human skull, pig teeth, donkey hooves,

mold, urine and dung. These ingredients were administered as lotions, pills, capsules, powders,

potions, ointments and suppositories, among other methods. Bloodletting started in Egypt in

1000 B. C. as well. Illness was seen as evil, and bloodletting was thought to get rid of the evil

from the body. This idea may have influenced the Greek idea of humors. There are four basic

humors of the body, blood, phlegm, yellow and black bile, and mucus. Each humor is secreted

by a different organ, and each had its own color, temperature and humidity. Each humor is also

associated with a temperament, and each person had a dominant humor. For example, a sanguine

person is dominated by blood, which is hot and moist. These people were believed to be obese

and full of laughter. A healthy person had all their humors balances, while an unhealthy

individual contained improperly mixed humors. This humor imbalance led to bloodletting, which

was believed to help restore the body's proper ratio of humors. (Shapiro and Shapiro, 4-7).

In Greece, incubation in a temple was believed to rid one's body of disease. Patients first

washed themselves, then lay down in the temple and waited to fall asleep. They were told to

dream of Asclepius, the healing son of Apollo. As they slept, a priest would enter and rub

ointment and herbs on the patient's diseased body parts. In the patient's dream or dream state,

Asclepius's serpent or dog would follow the priest and lick the ointment off the patient and

whisper remedies into the patient's ears. Patients would also be given advice for future

treatments (Shapiro and Shapiro, 6). It is unclear how patients were able to "see" Asclepius, but

one thought is that they were given sleep aids or hallucinogenic substances. One cure on record

was the delivery of a woman who was pregnant for five years (Retief and Cilliers, 841).

According to myth, when her child was born, he was four years old. After leaving the womb, the

child walked over to a fountain and started washing himself off As we know today, it is not

possible for a woman to be pregnant for five years. It is most likely that the woman did have a

long pregnancy, maybe a few weeks longer, and that as time passed, her story was exaggerated.

If the woman's pregnancy was longer than normal, it is possible that her child was more

developed than most newborns of the time, but he certainly would not have been able to walk or

bathe himself (Dillon, 242, 257). The Father of Medicine, Hippocrates, was working in Greece at

the same time people were visiting the Asclepian temples (Shapiro and Shapiro, 7). He believed

that medicine was an art, rather than a science (Jospe, 5). He produced the Hippocratic Corpus,

which was made up of about seventy essays on medicine and detailed over 100 vegetable-based

substances. His observational, common-sense theories were very different from the religious

theories based on temple visits and prayer as forms of treatment. Treatments usually included

fresh air, a good diet and bloodletting (Hippocrates believed in the idea of the four humors).

Medications were often administered as pills, ointments, inhalations and oils (Shapiro and

Shapiro, 7). He believed that diseases came from a natural cause, and he often used plants as

remedies. White hellebore was used as an analgesic, for pain management. Squirting-cucumber

juice was used to treat heart problems, rheumatism, paralysis and shingles. Dauke was used to

soothe the digestive tract and contract the uterus, delaying menstruation. Stinging nettle was

thought to treat anemia, heavy menstrual flow, arthritis, gout, sciatica and hemorrhoids. Mustard

seed was an antibacterial and an antifungal ("Hippocratic Use of Substances"). Modem science

has found that some of these natural remedies do have medicinal effects. According to WebMD,

white hellebore is used to treat cholera, gout, high blood pressure and herpes outbreaks ("White

Hellebore ... ").

The Roman Galen believed in the principle of opposites, "if a substance that causes or is

thought to cause fever, it can be used to treat chills~ if a substance causes emesis, it can be used

to treat constipation" (Shapiro and Shapiro, 11). During Galen's time, he used many different

techniques and medications (placebos). One infamous substance was theriac, which contained

more than thirty ingredients and took six months to produce. Its main ingredient was viper flesh,

and it usually contained opium. It was first produced as an antidote to poisons because it was

thought to draw poisons out of the body. As time passed though, theriac was used "as a remedy

for' almost every human ailment--chronic headache, hardness of hearing, dimness of sight,

blackout and giddiness, epilepsy, shortness of breath, spitting of blood, indigestion, nausea, liver

trouble, the stone; it strengthens the tongue, soothes delirium, is an excellent soporific, calms the

worries and stresses of the mind, is the only cure for tetanus'" (Shapiro and Shapiro, 12). The

end of the Galen era came with the popularization of cinchona. Cinchona bark was introduced to

Europe in the seventeenth century by Spanish Jesuits who brought it back from Peru. It was an

actual drug (it contains quinine, which is still used today to treat malaria) and was used to treat

malaria. It was first used as a treatment for any type of fever, but was later discovered to treat

only fevers caused by malaria. "Cinchona can be considered the first drug that was not a placebo

because it was specific for the treatment of malarial fevers and not useful for other fevers"

(Shapiro and Shapiro, 21).

Ideas of medicine varied in different parts of the world, but they also contained

similarities. In China, like in Greece, they believed in humors. The Chinese were focused on

symmetries and balance. They based everything on the five-element system, with the five

elements being water, fire, earth, metal and wood, and they strongly believed in yin and yang.

The main treatment techniques were acupuncture and moxibustion (burning ground leaves

placed on sticks or acupuncture needles and held close to the body). Uncomplicated diseases

were treated with five tastes, five kinds of grain, five substances and five flavors. Pungent and

sour flavors helped an ill liver, salty flavors were used for a weak heart, and sweet flavors were

used to drain the heart. People with ulcers received acupuncture with flint needles, while people

with internal diseases were treated with acupuncture with "poison medicine". Those exposed to

cold were treated with moxa, those with muscle numbness and tight muscles received fine

needles during acupuncture. Chinese people with chills, fevers or paralysis were massaged and

taught breathing routines. Acupuncture is still a large part of treatment in China today, though

not for the same illnesses. In India, main treatments were for lesions that could be physically

seen. Indian doctors would amputate limbs, repair ear lobes, stop bleeds with hot oil and suture

cuts with ant heads. Treatments also included mantras, dieting, the ability to "pull" one's mind

from bad thoughts, abstinence from sex and enemas (which used to be called clysterizations, and

were a way to remove evil bowl contents) (Shapiro and Shapiro, 9, 13).

Stories of unicorns existed in ancient China and Indi~ the Bible, and in the Western

world. Ground unicorn hom was believed to cure fevers, while hom jelly was thought to restore

strength in ailing people. This mythical creature's hom was also supposed to identify and protect

against poisons in wines and foods. The hom was seen as a cure for "poisons, fevers, bites of

mad dogs and scorpions, worms, fluxes, the plague, the falling sickness, memory loss, and all

other complaints; and was believed to assist the memory, fortify the animal spirits, and prolong

youth" (Shapiro and Shapiro, 14). People believed the hom came from a unicorn, but in reality,

the "hom" was the left, upper incisor tooth from a male narwhal. Unicorn hom was the most

expensive placebo in history, and during the sixteenth century, it sold for ten times its weight in

gold. Even after the true nature of unicorn hom was revealed, people still bought it and used it

(Shapiro and Shapiro, 15). Babylonians, Hebrews, Greeks and Romans used the mandrake as a

sedative, purgative, aphrodisiac and hallucinogenic. It was first referred to as an aphrodisiac in

the Bible. According to legends, the plant had magical characteristics. It looked like a man, and

would scream if pulled from the ground. Hearing the scream of a mandrake was believed to

cause insanity or death, so a loud hom was played to drown out the shrieking while the plant was

being collected. Shakespeare mentioned the mandrake in his plays, and in Romeo and Juliet he

wrote '" And shrieks like mandrakes tom out of the earth! That living mortals hearing them, run

mad'" (Shapiro and Shapiro, 15). Today, people may know of mandrakes from lK. Rowling's

Harry Potter series, in which they are used as a cure for those who are petrified.

"The most powerful element underlying these therapeutic procedures was the placebo

effect, possibly enhanced by the emotionally charged and elaborate ritual" (Shapiro and Shapiro,

6). When people could not explain their suffering or illness, they made up ways to make it go

away. The only reason people could think of to explain pain and suffering was God, that they did

something wrong. Sickness was a punishment. "From humanity's earliest beginnings, the

appearance of disease had an inseparable link with religious feelings and thoughts" (Jospe, 1).

People prayed to the gods for cures, they used magic incantations and they sacrificed to the gods.

Relief from pain and suffering could not happen without divine intervention (Jospe, 2). This idea

can be seen in many different, ancient cultures. One of the oldest, and possibly most well known,

treatments is the laying of the hands. According to the Bible, this was first practiced by Jesus

Christ. His touch was able to heal people, and it is believed that he cured "blindness, dropsy

(edema), leprosy, stroke and insanity" (Shapiro and Shapiro, 17). Christ was also able to perform

exorcisms, to rid people of demons possessing them, by touching them. Many after Christ used

to power of touch, Roman emperor Vespasian, Norse King Olaf, King Clovis of France, King

Edward the Confessor and King Charles II. The royal touch was done by marking a cross on the

patient, and it cured the King's Evil (any disease of the time). King Charles II supposedly healed

the most people with his touch, some 100,000 people. It is believed that to reduce the risk of

failure, patients were screened and carefully selected before they were touched. There is

documentation that the touch seldom worked, and people would return to the king many more

times for treatment. Later some commoners believed they had the healing touch. The most

famous of these was Bridget Bostock who was known as the "healer of Coppenhall". She

touched seven hundred people a day, including those suffering from "hysteria, dyspnea, palsy,

and almost everything else, never accepting remuneration for her ministrations" (Shapiro and

Shapiro, 18).

In the seventeenth century, medicine made huge advances but is still considered

primitive. The act of bloodletting was still practiced. The dean of faculty at the University of

Paris bled his wife from the chest twelve times to cure her fluxion (excess fluid), he bled his son

twenty times for a fever, he bled himself seven times for a cold, he bled one friend thirty-six

times for a fever and he bled another friend sixty-four times for rheumatism. Mistletoe from oak

tree was thought to cure falling sickness (epilepsy), edema, impotence, leprosy and syphilis

(Shapiro and Shapiro, 23-24). The eighteenth century has been described as '''laying the

foundations for modem or scientific medicine'" (Shapiro and Shapiro, 24). The small pox

vaccine was discovered, as was a study showing that citrus fruits prevented scurvy. The 1700s

were not without placebos though. Clysters (enemas) were a popular procedure and the "doctrine

of infarctus" stated that constipation was the cause of most human illnesses. When George

Washington had a cold and a tonsillar abscess, he was bled 2.5 to 2.8 quarts, injected with

calomel (thought to be a purgative), given emetic tartar (also believed to induce vomiting), he

inhaled vinegar water vapors, his extremities were blistered and a plaster mixture of bran and

vinegar was spread on his throat over an existing blister. This treatment would have severely

dehydrated George Washington, and it is believed this is what killed him. With the nineteenth

century came allopathy, homeopathy and eclecticism. Allopathy used selected substances to

produce effects opposite to symptoms of the disease. For example, to treat malaria and

dysentery, purging with colonies were used until the patient collapsed. Homeopathy was based

on the Latin principle of similia similibus curantur ("like curses like"), or the idea that the power

of medicine depended on the likeness between the symptoms produced by the medicine and the

symptoms of the disease. Homeopathy also believed that drug action was effected by dilution,

and the recommended dosage was at the thirtieth potency. Similar to homeopathy was the

principle of signature of drugs, which was based on astrology and stated that "the stars impress

the 'signatures of disease' on drugs, and that the signatures are manifested by the form and color

ofthe plant from which a drug is obtained" (Shapiro and Shapiro, 26). Nutmeg, which resembles

the shape of a brain, was used to treat diseases of the brain. Eclecticism was the idea of adopting

whatever substance was found beneficial, essentially taking any combination of seemingly useful

substances, which usually ended with overtreatment and toxic effects. Towards the end of the

nineteenth century, doctors were skeptical about medical treatment and were very pessimistic

about drug treatment. The "New School of Medicine" was developed at the end of the 1800s and

was characterized as having "frrm faith in a few good well-tried drugs, little or none in the great

mass of medicines still in general use ... It is more concerned that a physician shall know how to

apply a few great medicines which all have use, such as quinine, iron, mercury, iodide of

potassiu~ opium and digitalis, than that he should employ a multiplicity of remedies the action

of which is extremely doubtful" (Shapiro and Shapiro, 27, 24-27).

Throughout the history of medicine, progress shifted from treating spirits and demons to

treating symptoms. The collective, nonspecific "illness" that could affect anyone and everyone

no longer existed. Instead, doctors focused on maladies and specific organs and sites of infection.

Nineteenth century pathologist Virchow said, "'There are no general diseases, only diseases of

organs and cells '" (Jospe, 6). Diagnoses were based on order, and diagnostic categories were

created. Sicknesses were traced back to their origin and were diagnosed based on the category

that best described them. Once this was completed, doctors needed a treatment plan that was

specific to each case (Jospe, 6). "Sickness was not something that attacked the whole person, but

merely an organ, or a few cells" (Jospe, 6). Therapy became more rational and effective. There

were fewer medications for psychological treatments, so inert substances were used instead. The

idea of psychological factors playing a role in illness and disease exploded onto the scene with

the introduction and success of Christian Science, homeopathy, hypnotism and psychotherapy.

Inert substances may have been popular to differentiate a prescriber from a homeopathist. The

idea of an inert placebo came about in the 1890s, but placebos were not medically inert until

years later (Shapiro and Shapiro, 34). Increases in technology allowed for better microscopes,

surgical sophistication, and overall, diagnosis (Jospe, 6). Medical journals began publishing

more controlled trials than uncontrolled trials. Inert placebos were given as the control on single­

blind studies. Double-blind studies evolved from inadequate single-blind studies, which allowed

for more control. "The rationale was that the inert placebo, under double-blind conditions, would

provide a control for spontaneous change and psychological and other variables and would

permit clear-cut differentiation between active and inactive treatments" (Shapiro and Shapiro,

34). Double-blind placebo controls played an important role in tuberculosis studies in the 1940s

and poliomyelitis studies in the 1950s. Today, a placebo is "any therapy that is intentionally or

knowingly used for its nonspecific, psychological or psychophysiological, therapeutic effect, or

that is used for a presumed specific therapeutic effect on a patient, symptom, or illness but is

without specific activity for the condition being treated" (Shapiro and Shapiro, 41).

During the nineteenth century, the definition of "placebo" was limited to medicine. In the

first half of the nineteenth century, nondrug treatments were not popular and not often used. This

was reflected in treatments used by quacks, who used drugs. Quacks often exploited legitimate

areas that were developed by scientific medicine, so the nineteenth century was "the great age of

the patented, secret preparation, or nostrum, and the predominant quack activity during that

period was the use of these drugs" (Shapiro and Shapiro, 33). The word "quack" comes from

"quacksalver", which means one who boasts about the virtues of salves and ointments. The term

came about when using mercury became popular in Europe and non-doctors started using it.

These non-doctors were called quacksalvers and they were very unethical. They would

incorporate illegal drugs or alcohols into their "medicines" to develop and sell fake treatments.

Quacks have been around as long as physicians have. Francis Bacon was quoted as saying, '''The

weakness and credulity of men is such that they often prefer a mountebank, or a cunning woma",

to a learned physician ... For in all times, witches, old women, and imposters, have, in the vulgar

opinion stood competition with physicians'" (Shapiro and Shapiro, 43). Health quackery is

dangerous because it relies on "exploitation fear in the patient; the promise of painless treatment

and good results; claims of miraculous scientific breakthrough; the proposal of one cause and

one therapeutic system to end confusion and doubt to make a complexity simple and

comprehendible to the untutored mind" (Shapiro and Shapiro, 44). Quacks are still around today.

Many can be seen trying to sell diet pills or weight loss wraps on television commercials and in

popular magazines.

Religious treatments have been and will be ever prevalent in our society. As mentioned

earlier, during the Middle Ages, the Catholic Church promoted the healing power of Christ.

Early Christians thought that diseases and plagues were punishments from God, for bad

behavior. Laying of the hands and exorcisms are still used today (Shapiro and Shapiro, 45).

Exorcisms had become a "persuasive tool for demonstrating apostolic authority" (Kaptchuk,

Kerr and Zanger, 2); they were miracles. In 1599, in a small French town, King Henri VI wanted

to find out if people were really being possessed by demons and if exorcisms really worked. A

local family claimed their daughter was possessed by the deviL Henri VI sent someone to

perform an exorcism, but not a public exorcism that was common practice, a private ritual. It is

thought that the public aspect of exorcisms lead to coercion and false testimony from patients. In

the private exorcism, the girl was secretly administered real holy water for several days, with no

effects. Then she was given regular, non-holy water from a special flask and she seethed in pain

when the water touched her skin. She was touched with a regular piece of iron in the shape of a

cross (not a true cross), taken out of an adorned case, and she fell over in agony. The priest read

to her in Latin, telling her he was reading from the Holy Scripture when actually, he was reading

from Virgil's Aeneid, and the girl twisted in discomfort (Kaptchuk, Kerr and Zanger, 2).

Benjamin Franklin and Antioine Lavoiser used the first ever placebo-controlled

experiment to disprove the healing practice of mesmerism in 1784. Mesmer was a physician who

developed a curative healing technique after determining that he could obtain results similar to

those of an exorcism, but without using the power of Jesus and the church. During this time,

exorcisms were only successful when done by priests. Mesmer alleged the invention of "animal

magnetism" (called mesmerist), which was a fluid analogous to gravity. Objects were

mesmerized, which gave them the ability to heal those who touched the object. Placebo­

controlled experiments were completed by Franklin and Lavoiser using either "bogus"

mesmerized objects, in which patients believed non-mesmerized objects to be mesmerized, or

secretly mesmerized objects, in which patients did not know an object they touched was

mesmerized. The results of the experiment were that <"this agent, this fluid has no existence' and

any effects were due to 'imagination'" (Kaptchuk, Kerr, and Zanger, 1). Franklin referred to

these placebo-controlled trials as "trick trials". Much like exorcisms and laying hands is the idea

of the therapeutic touch.

Therapeutic touch is the belief that the "physical body is surrounded by an aura (energy

not visible to normal vision) and is penetrated and kept alive by a universal energy called prana

(a Sanskrit word meaning vitalforce) that flows through the body and is transformed by chakras

or non-physical vortices" (Aghabati, Mohammadi, and et ai, 376). The term was first used in

1973. The idea is that energy imbalance leads to illness, so one always needs to be in balance.

People give off energy fields by way of wave patterns; rhythmic energy waves are the best for

re-ordering the body's field. Some symptoms that occur when one is imbalanced are energy

blockages, congestion and dysrhythmias. Therapeutic touch is a technique that is learned;

sensitivity to energy is learned. We do not have any technologies that can detect human energy

fields. "One is able to develop this sensitivity through a process called 'centering', the attainment

of a mental state in which the practitioner quiets the mind, detaches from inward and outward

distractions, and focuses full attention and intention on helping the patient" (Aghabati,

Mohammadi, and et aI, 376). Therapeutic touch is believed to relax patients, decrease anxiety

and depression, decrease pain and boost the immune system (Aghabati, Mohammadi, and et ai,

379). The placebo effect is thought to be present in therapeutic touch. It is suggested that because

some people believe in the healing power of the therapeutic touch, they feel better. Therapeutic

touch research is controversial because some studies have shown it is beneficial, while others

have disproved its methods.

Another controversial topic involving the placebo effect is snake handling. Snake

handling in the South-Eastern United States began in Tennessee in 1910. George W. Hensley

observed a man handling a poisonous snake without being bitten and after thinking about what

he saw, he came to the conclusion that the snake handler was acting just as Mark did when

instructed by Jesus before the Ascension. Hensley believed that Mark 16: 18, which stated, "They

shall take up serpents", was a command. From that point onward, Hensley thought in order to be

worthy of life after death, he had to take risks. The risks he took were handling snakes. After this

realization, he caught a rattlesnake in the mountains. His followers believed that "God granted

Hensley a strange power that day to render the reptile harmless. And from that hour, Hensley

was to become a voice crying in the wilderness" (Kimbrough, 40). If one was truly faithful to

God, he/she would not be harmed by a poisonous snake. If someone were bitten, they were not

really faithful. Hensley established a church, which he called the "Church of God" (Kimbrough,

40). People still practice the act of snake handling today. The placebo effect and snake handling

deals more with religion than science, so it's difficult to disprove its effects. A believer can say

they were not bitten because they believe in God and his powers. This belief is difficult to argue

with and disprove using science. Scientists may feel that believers who do not actually touch the

snakes maybe still believe in the powers of the handlers (and ultimately, God) because of the

placebo effect; they believe it to be true, so it is true.

Placebos and the placebo effect have survived thousands of years and have become

especially important today. Placebo responses have been seen in studies of the endocrine system,

the immune system, the respiratory and cardiovascular systems and the brain. In one study,

researchers presented patients with flower allergies with "fake" flowers (artificial flowers with

no pollen), and the patients showed allergic reaction symptoms. Immune placebo responses have

also been present in studies with a paired solution of sodium saccharin and immunosuppressive

drug cyclophosphamide. Mice have been conditioned with this pairing. Then, when patients were

presented with just the sodium saccharin, their immune systems responded as if the

immunosuppressive drug was present. This study was done with patients with lupus

erithematosus and multiple sclerosis. Similar results have been seen in hormonal responses

(Price, 580).

Postoperative patients were given buprenorphine, an analgesic, to mildly reduce lung

ventilation. A placebo was found to mimic this response of decreased ventilation. This placebo

effect can be completely blocked by naloxone, which is an opioid (an inhibitor), indicating that

this response is mediated by endogenous opioids. In experimental ischemic arm pain, an

analgesic placebo decreased heart rate. "Both the placebo analgesic effect and the concomitant

heart rate decrease were reversed by the opioid antagonist naloxone, whereas the P-blocker

propranolol antagonized the placebo heart rate reduction but not placebo analgesia" (Price, 581).

There are two possible mechanisms for this effect. The response is a consequence of the pain

reduction itself, or the placebo-activated endogenous opioids might inhibit the cardiovascular

system directly (Price, 581).

In a recent Parkinson's disease study, patients were given a placebo (inert substance) and

told that the substance was an anti-Parkinsonian drug that would improve motor function.

Patients did respond to the placebo treatment and showed improved motor function. Using

positron emission tomography, endogenous dopamine levels were evaluated. The results showed

that placebo-induced expectation of motor improvements activated dopamine in the striatum of

Parkinson patients. In Parkinson patients who had electrodes implanted deep in their brain for

stimulation, hand movement was found to be faster when patients expected good motor

performance. Depression is another area of recent study. Depressed patients given placebos

showed electrical and metabolic changes in the brain. In patients with unipolar depression,

increase metabolic changes were seen in several different areas of the brain after placebo

treatment. These same areas of the brain were affected by selective serotonin reuptake inhibitor

fluoxetine, suggesting that a possible role of serotonin in antidepressant placebos (Price, 582)

There are other factors that play into the placebo effect, including patient attitude

toward a therapy or drug, doctor attitudes about the treatment, and doctor/patient relationships.

Patients who believe a therapy or drug will work are more likely to have a placebo response.

Patients who trust their doctor's decisions will more likely have a positive placebo effect and

respond to placebo treatment. Physicians who are likable, physically attractive and competent are

associated with favorable placebo results (Shapiro and Shapiro, 22 I -223). The placebo effect is a

real occurrence. Many, many studies completed over time have proven this fact. In the future,

placebo studies will be very important in finding cures for depression, Parkinson's disease and

other illnesses.

"Implicit in the placebo effect is the recognition that patients bring to the healing process

their own attitudes and belief systems, which can be stronger than the specific action of the drug"

(Shapiro and Shapiro, 237). There is still research left to be done. We still don't know about the

mechanisms or mediators that contribute to the placebo effect. "The future challenges for

placebo research encompass neuroscience, clinical practice and social psychology" (Colloca and

Benedetti, 551). There are several techniques that can be used to find relationships between the

brain and the placebo effect, including in vivo receptor binding, recording neurons in awake

patients and using imaging with electrophysiological techniques. New clinical trial designs are

also necessary, to try to find out the mechanisms behind the placebo. "Research in this

area is still in its infancy and many questions remain unresolved ... However, there is compelling

reason to believe that, in light of the rapid advances in placebo research in recent times, the

coming years will be characterized by a real attempt to place the placebo effect in an emerging

science of mind-brain-body interactions. (Colloca and Benedetti, 545).

Appendix

Posted completed for thesis. Presented at the Spring 2012 Physiology Poster Session for

Undergraduates at the University of Arizona.

40,000 B.C. - 1500 B.C.

Placebo effect i ! I!

occurred during CrO-Magnon times. Skulls were trepanned, which involved drilling a 2.5 -5 centimeter diameter hole into the skull. The surgery was

thought to free "bad spirits" from the body. TIlis technique was used until

the 18th cenhlry,

2100 B.C., Sumerian clay tablet containing 1 5 remedies, today viewed

as placebos. TIlese included lotions. wines and plasters. Most of the remedies were vegetable based.

Jessica Wagstaff and Zoe Cohen. Ph.D. Department of Physiology

University of Arizona 1000 B.C. - 300 B.C.

1000 B.C., Blood letting started in Egpyt and may have influenced the idea of Greek humors, Bloodletting

released evil from the body.

100 A.D. - 1700s

100/200s-A~r:5:. 'G~len· believed in the principle of opposites. If a substance

was thought to cause fever. it could be used to treat the chills.

1800s - Future ,

"placebo" appeared in Fox's New A1edjcal[)lctiona~

1900s. Snake handling became 400s B.C.. The word "placebo' first 1200s. "Placebo" appeared in the King I popular in the South-Eastern United

appears in the Hebrew Bible as James version of the bible in the phrase States. It's believed that if one has true etlzalekh "Placebo Domino in regione vivol1lm" , :1 faith, he/she can handle poisonous

TIle theory of humors was started by which translates to "1 will please the snakes without being bitten. the Pythagoreans, and later influenced lord in the land of the living". . 1940s/50s. Double-blind placebo

Hippocrates and Galen. J .: studies played an important role in Chinese medicine was also built on the f Laying of the hands was a very popular Li tuberculosis and poliomyelitis studies.

. theory of humors. % treahn~nt. for many diseas~s. It was first ~,:1 1970s. Therapeutic touc~ was HIppocrates, the Father of Medicine, practiced by Jesus Chnst. Many ~j developed. It's based on the Idea that

1500 B.C., Egyptian Ebers PapYl1ls produced the Hippocratic Corpus, emperors and kings b~lieve~ they had ~ the body has am energy aura that can • . documented 842 prescriptions and which contained 70 essays on the power to heal WIth theIr hands, '. be altered and become imbalanced.

700 substances made from vegetables, medicine I called the royal touch. animals and minerals. '111e documents Future. Research is needed to find the detailed how to cure a headache, how 300s B.C .• Patients slept in a temple 1700s, Clysters were used to treat ,J relationship between the placebo .

to evacuate the belly and how to and w~re told to dream of Asclepius, ,', constipation, which wa.s th~ught to il,j effect and mechanisl~s/mediators in remedy the bowels. the healmg son of Apollo, to heal them. ! cause most human Illnesses. 'I:f the bram .

.... _ ... Priests l1lbbed ointment on patients as 1784 •. Benjamin Franklin and Antioine Double-blind studies will be they slept. LaVOlser used the fIrst ever placebo- important in finding cures for diseases

controlled experiment to disprove the such as Parkinson's disease or ' effects of exorcism. ~, depression.

=

w

~

'"" , .......... v. TIlcrapeutic Touch on Fain and Fatigue of Cancer Patients Fntler&oJng Chemofherapy.' Evidcnt't: -Ba.flt!d (70mp!eIIk.'nlluy IlJld Allcnllffivc Akdk..';'m .. ', 7 3 (:lOOJ3} 37:)-381 , Wch. 27 ,\tar. 2012 . DoIli.H~er , Andre .• Ancient t~l)twi Medicine.' An introduL:ti,w to!he IU:ftOry and culture of Pho.nlOlIK 1«>7,t ~V. , Janltary 2000. Wen. I .\'ov :,w i l <http.f!ww"w.n:sha.fim.orgjljKdiC'·gyplftimdincs!topit.:~jmcdicinc .h lm> _. Kltptchuk Too J. Cuthcrlne [Kerr , and Abhy i'..angcr 'rhu;coo Conl rois. [xord.snu alkl the. Devil: LsJKW 3 7·t~)(';97 (.l009). l - ~ \Veh. 2 1 Feb. 20 12. . Price. Donald P . el " L . A Compreht!nsi"c Review of the r~oo rlfoct. Recent .'\d\'tln1..'cs lUid CUJTC nt nlOIl~ht: AmllltU Rel'1f:w of PJ)'t"ho/ogy 5~) . (l OOS). Gi; ~ - 5 ~)Q . Well. " Apr. 20 12" Sclblxll ini. Re n.tIO M,t; .. r hl). · " t.ak in~ Hole;:.., in Iltt: Skull, Andcnl Psychosllixery't ' !lrai" "( ,\1ind .' fJl,J?IVJ nl;.'. ,I uI IC 1 ~97, Weh 8 0 d 201 1 < http .jfv.rv.,"V,fcc rehro ll"!lltc .o r)l; .l'rJlIOl .lhistonu.ltn.:pan .hlm> " SIu.\ \i l'O. :o-.\ D. Arthur t:. .. and I]aine Shl.lpi l"O . Ph () 11", fo\Nt'rfu l P1tic..--..:.ho. lla\timore. :\ H\ TIle Johns Hopkins l' ni\"c rsit)' !'rc~ 1 ~)97 . rrilll. [!luxes, i::l i' .~'.: ,:, 11<('1 \ ,'In, !!: ',; :'1 .>" j. i' ~'~ \ ~ ! In hi ti d. ;:'!:' d'h !i ::. h: 'l ,; - :. S \ ..... <. , !" 1"'·I;·f 1' .. \1 ' I'.' :111111 r" -1', f i ' l'~

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