Ladies and gentlemen, have you ever taken a pill that you believed would cure your

headache? If so, you may have experienced the power of the placebo effect. Similarly,
have you ever felt worse after taking a medication or receiving a treatment, even though
the intervention itself had no harmful effects? This is known as the nocebo effect, and it
can have a powerful impact on our health and well-being. These effects have long
captured the attention of medical researchers, healthcare providers, and the general
public, as they highlight the intricate interplay between the mind and the body.
In this talk, we will explore the mechanisms behind the Placebo and Nocebo Effects, as
well as their applications and the ways in which they impact our health.
First of all, we are going to start with some background and what involves Placebo.

Placebo is Latin for 'I will please' and refers to a treatment that appears real, but is
designed to have no therapeutic benefit. A placebo can be a sugar pill, a salt water
injection, or even a fake surgical procedure. In other words, a placebo has no therapeutic
properties. Placebos are often used in medical research and clinical trials to help scientists
evaluate the effects of new medications.
The placebo effect is a phenomenon where people report real improvement after taking a
fake or nonexistent treatment, called a placebo.
The first scientific demonstration of the placebo effect came in 1799 when a British
physician, John Haygarth, set out to test one of the quack remedies on sale at that time:
expensive metal rods named Perkins tractors that purported to draw disease from the
body. Haygarth pitted these rods against sham, wooden Perkins tractors that looked just
the same as the 5-guinea ones on sale, and found that 4 of 5 patients with rheumatism
reported that their pain improved. (He published his findings in a book, On the Imagination
as a Cause and as a Cure of Disorders of the Body) (eso es lo que querías quitar?)

MECHANISMS
1. Placebo effect can activate the release of natural painkillers in the brain.
The Placebo effect is mediated by the release of endorphins and other neurotransmitters
in the brain. When a person receives a placebo, they may experience a release of these
natural chemicals, which can produce feelings of pleasure and reduce pain and stress.
2. It can stimulate the immune system.
The placebo effect can stimulate the immune system through several mechanisms. One
possible explanation is that the placebo effect may activate the hypothalamic-pituitary-
adrenal axis, which is a key part of the body's stress response system. When a person
receives a placebo, they may experience a stress response, which can trigger the release
of cortisol and other hormones that can affect immune function.
Another possible mechanism is through the activation of the cholinergic anti-inflammatory
pathway, which is a pathway that regulates inflammation in the body. It is thought that the
placebo effect may stimulate this pathway, which can lead to a reduction in inflammation
and improved immune function.

APPLICATIONS
1. Clinical Trial
In clinical trials, placebos are used as a control group to compare the effectiveness of a
new treatment to a non-active substance. The use of a placebo group helps researchers to
determine whether any observed effects are due to the actual treatment or simply due to
the placebo effect.
The use of placebos in clinical trials is important for establishing the safety and efficacy of
new treatments. It helps to ensure that any observed improvements are due to the
treatment itself, rather than simply due to the placebo effect.
2 Complementary Therapy
Placebo can be used as a complementary therapy in conjunction with conventional
medical treatments. It can help to enhance the patient's perception of the treatment,
increase their belief in its effectiveness, and promote a sense of control over their illness.
For example, a patient with chronic pain may receive a painkiller medication as well as a
placebo pill. The placebo pill may have no active ingredient, but the patient may perceive it
as an effective painkiller due to the placebo effect. This can lead to a reduction in their
overall pain levels and an improved sense of well-being.
Placebo can also be used in psychotherapy, such as cognitive-behavioral therapy, to help
patients overcome mental health conditions such as anxiety and depression.

(Transition: Placebos, in addition to producing beneficial effects, can also cause

undesirable effects or adverse reactions, known as the Nocebo effect.)

The Nocebo Effect refers to the phenomenon where a person experiences negative side
effects or a worsening of symptoms after being exposed to a treatment, intervention, or
other stimulus that has no known pharmacological or physiological effect on the body.
A nocebo effect can occur if a person takes a real or active medicine and can also occur if
they are given a placebo.
This expectation of negative effects may be triggered when a patient is told which adverse
effects they might experience before starting treatment.

MECHANISMS
Expectation Bias
One of the most important factors contributing to the nocebo effect is the expectation of
negative outcomes. When a person expects to experience negative effects from a
treatment, their mind and body may respond in a way that creates those effects, even if
the treatment is harmless. Their brain can activate the body's stress response system,
leading to the release of stress hormones and physiological changes that can cause real
symptoms and negative effects.
Psychological factors
Anxiety and stress: Negative expectations and beliefs about a treatment can cause anxiety
and stress, which can affect the body's physiological responses. Anxiety and stress can
activate the sympathetic nervous system, which can lead to an increase in heart rate,
blood pressure, and other physical symptoms.
Conditioning:
Another factor that may contribute to the nocebo effect is classical conditioning. If a person
has experienced negative side effects from a treatment in the past, they may associate
those side effects with the treatment, and expect to experience them again in the future.
Neurotransmitters
Research suggests that the nocebo effect may be related to changes in neurotransmitters
in the brain, such as dopamine and opioids. Dopamine is associated with reward and
pleasure, and when a person expects negative outcomes, dopamine levels may decrease,
leading to negative feelings and physical symptoms. Opioids, which are associated with
pain relief, may also play a role in the nocebo effect by modulating pain perception.
Negative beliefs and expectations can lead to a decrease in these neurotransmitters,
which can affect mood and physical symptoms.

NOCEBO IN CLINICAL PRACTICE

Some studies have shown and quantified the nocebo effect in various everyday situations
such as the ones presented below:
1. Reading the Package Insert
A package insert is a document included in the package of a medication that provides
information about that drug and its use.
Reading the package insert is one of the main sources of negative expectations capable of
causing a nocebo effect. For example, it has been observed that lactose-intolerant patients
experience gastrointestinal discomfort when they discover from the package insert that the
drug contains lactose, even though the amount is minimal.
2. Informing patients participating in a clinical trial about potential adverse events
Informing patients participating in a clinical trial about potential adverse effects can
dramatically increase the number of patients who experience them.
A case has been documented of a patient who ingested 29 capsules during a trial
believing he was taking an overdose of antidepressants. The patient was admitted with
severe hypotension requiring intravenous fluids to maintain blood pressure. The adverse
effects resolved quickly when the blind was unblinded and it was discovered that he
belonged to the placebo group.
3. Media Coverage of drug warnings
The appearance of media reports of drug alerts can rapidly affect patients' expectations
about their treatment. Several studies have shown an increase in reports of adverse
treatment effects when a drug safety alert is broadcast as television news.

CONCLUSION
In conclusion, the placebo and nocebo effects are fascinating phenomena that
demonstrate the mind's power over the body. Placebo effects can produce positive
outcomes, while nocebo effects can lead to negative outcomes. Understanding these
effects is crucial in medical research and clinical practice, as it can help healthcare
professionals optimize treatments and improve patient outcomes.
Ultimately the placebo and nocebo effects highlight the importance of the mind-body
connection and the impact of beliefs and expectations on health and well-being.