Placebo agent is already familiar to many people. Most of the understanding of placebo comes from [randomized double-blind controlled] experimental settings in medicine. Placebo and placebo effect have caused great discussion and controversy throughout the history of medicine, and have continued to this day. What are the characteristics of placebo effect? As a substance that should not produce any biological effects, it works through what? What factors can affect the placebo effect? Is placebo therapy clinically and ethically appropriate for patients?
The history of placebo
The word Placebo comes from Latin and its original meaning is [to make pleasure]. It first appeared in the Great Dictionary of New Medicine published in England in 1785 and has clearly pointed out that [placebo is a common method in medicine]; Presumably, Long before that, sharp doctors discovered that, Such as the doctor’s words and suggestions, the patient’s psychological state and so on have obvious influence on the disease condition. Placebos have been widely used by doctors for a long time. At that time, few people thought it would damage the reputation of medicine. There is evidence to prove the existence of placebo effect when British doctor Hegas carried out the world’s first placebo-controlled trial in 1801. Dr. Hegas examined the instruments used to treat diseases such as arthritis at that time. The Perkins aspirator is a tapered metal rod, It was invented by American Dr. Perkins in 1795. He also applied for a patent for it, He claimed that the metal rod was made of a special alloy, The pain can be removed by rubbing on the painful part for half an hour. Although the Connecticut Medical Association later accused him of cheating patients and expelled Perkins from the Medical Association, But Perkins became popular all over Europe with his inventions. Make a lot of money, Even Thomas Jefferson, then president of the United States, believed this. However, Dr. Hegas simply changed the material of Perkins aspirator into wood. It is found that those patients who have an effect on [the real Perkins attractor] are equally effective with these fake wood products. Doctors stressed in the paper that doctors should realize the magical and powerful influence of this mind on physical diseases.
The placebo effect is a medical freak. Since placebo itself is defined as [an inert substance with no physiological activity], it should not have any therapeutic effect. This paradox lasted until the second half of the 20th century, when people began to understand enough psychology and neurobiology to understand the way placebo works.
Placebo Effect: Psychological Factors Are More Important-I Hope [Medicine] [Disease Removal]
The purpose of general placebo-controlled clinical trials is to verify the efficacy of drugs. There is a special type of study on placebo, It focuses on various factors that affect the placebo effect. Placebo effect has been the most widely studied in the field of analgesia. But the placebo effect does not appear in everyone, Only about 30% of people respond to fake analgesics. Many patients need analgesics after surgery. However, if the patient is injected with placebo such as normal saline first, And told the patient that it was an analgesic, The patient’s demand for analgesics will decrease. If the patient is not told through words that the placebo injected is an analgesics, Then there will be almost no analgesic effect, The patient still needs enough painkillers. Through the automatic drug syringe pump, It was found that if the patient was told in advance that the pump had started injecting drugs now, Compared with patients who do not know that they have started injecting drugs, Much more effective. No matter what kind of analgesic it is, It is much better to play in the open than in the dark. Besides, If the pain itself changes, At the same time, people will think that the drug therapy is effective. The next time they encounter the same degree of pain, the patient will think that the pain is not as strong as it was at the beginning. That is to say, if the patient knows that the treatment will be carried out, the following effective treatment will be more effective.
As the saying goes, being positive about your illness helps you recover. Patients with positive emotions not only believe in the effect of drugs, but also estimate what kind of condition they will recover from their illness. Research data show that [believing in drugs] and [hoping to get better] have a 1 +1 > 2 effect on analgesia.
In popular terms, it is not only the degree to which the disease is expected to be treated, but also the strength of the imagined drugs to combine them. Moreover, it was later discovered that this group of people who will have placebo reactions tend to have higher levels of both.
[I hope my pain will disappear] and [I think this medicine must be very effective] are the placebo effects. These phenomena show that, All kinds of psychological cues are the main source of placebo effect. These effects can be transmitted to patients through doctors’ words. It can also be influenced by the patient’s own improvement of the disease and the effectiveness of the drug, and even can establish the analgesic impression of placebo through conditioned reflex. Two independent factors at the conscious and subconscious levels are the main psychological factors that determine the placebo effect.
Anti-placebo effect-trouble caused by unnecessary worry
Since there are effective placebos, are there any opposite [anti-placebo] and anti-placebo effects?
This phenomenon is actually a sibling of the placebo effect, and it is his dark side. In medicine, it also comes from Latin nocebo, which means [I shall harm]. In fact, placebo and anti-placebo are exactly the same thing, while in medicine, the effects are completely opposite, the positive is placebo, while the negative worsening effect is anti-placebo effect.
As mentioned earlier, a large part of the determinants of placebo effect are psychological environment factors, so these two effects can appear not only on inert substances, but also on any effective drug.
Almost everyone will pay close attention to the side effects and adverse reactions of drugs before taking them. The safety of modern drugs is highly guaranteed. However, there are still many [side effects] and [adverse reactions] that are not within the scope of drug action. According to statistics, only one tenth of all recorded adverse reactions are definitely caused by the drug, and the others cannot be determined whether they are related to the effect of the drug itself.
Most of these symptoms are medically classified as non-specific symptoms, It is very common, but it cannot be inferred from these symptoms that you have what, and these symptoms often do not have serious organic diseases, such as dizziness, weakness, drowsiness, nausea, etc. Think carefully, do people have these conditions most of the time, but there is no serious illness? If ordinary people are surveyed, a quarter of them will report inability to concentrate, a quarter will report drowsiness, 14% will report headache and 5% will report dizziness.
There are reports that nearly a quarter of the placebo group in various clinical trials will say that they have various side effects. In 109 double-blind trials, 19% of the healthy people reported adverse reactions on themselves. Even more strange phenomena occurred. In some almost asymptomatic diseases (such as hypertension), the placebo group reported more adverse reactions than the real drug group!
A study analyzed and concluded that the manifestations of a large number of anti-placebo reactions were: 7% headache, 5% drowsiness, 4% fatigue, 1% dizziness and nausea respectively, and other studies believed that the proportion was much higher: 25% of placebo users had drowsiness, 17% fatigue and weakness, 16% gastrointestinal reactions, 13% lack of concentration and 12% headache. In short, the probability of anti-placebo effect is not small.
The placebo and anti-placebo effects produced by placebo share the same mechanism. Anti-placebo is equally vulnerable to being influenced by others and self-suggestion.
For example, if an allergic person is injected with normal saline subcutaneously but told that it is an allergen, It is very likely to induce his allergic symptoms. Some side effects can also be preserved through conditioned reflex. For example, cancer patients have previously received chemotherapy, Severe malignant vomiting and other reactions occurred, and after receiving other drugs or even placebo, up to 30% of the patients would have severe vomiting reactions, indicating that taking drugs would induce vomiting, which has been firmly remembered by the body by conditioned reflex effect.
In addition, in people with negative emotions such as anxiety and depression, The anti-placebo effect is more pronounced. If a drug is widely known, His side effects will also be widely known and amplified. Penicillin is an excellent example. Because penicillin is usually used in large doses, it is forbidden to use it once allergy is very dangerous. In fact, some people have carefully studied that more than 90% of adults and children who claim penicillin allergy are at least tolerant to oral penicillin.
Does placebo mean that psychology determines physiology? No!
Since placebo is related to a variety of psychological factors, the magnitude of placebo effect should also be determined by corresponding neural activities.
Opium is an ancient and important analgesic drug, Although it is also widely known as a drug. The brain can secrete a substance similar to morphine, the active ingredient of opiates. Endorphins, called endorphins, are secreted automatically when the body is injured to protect the pain it feels within a certain range. Naloxone, which is used for detoxification, also antagonizes endorphins. After the subjects were injected with naloxone, the placebo analgesic response disappeared.
There is also a neurotransmitter called cholecystokinin (CCK), It is a naloxone-effective substance produced by the human body itself, It can prevent the analgesic effect of endogenous opioid peptides. However, proglumide, an inhibitor of CCK, can effectively enhance the analgesic effect. However, interestingly, If proglumide is injected first and then a little naloxone is given, according to the previous analysis, the two should offset each other, that is, the CCK system no longer works. However, the experimental results are not the same, and the CCK system is still effective. Further research has found that CCK has more effect in preventing negative factors from inducing reduced drug efficacy and anti-placebo effect.
On the right side of the figure below are functional magnetic resonance images of placebo analgesia. When the pain is shown, Placebo administration can effectively reduce neural activity in areas related to pain perception. Brain activity areas that determine pain, Including thalamus, anterior insular lobe and anterior cingulate gyrus, also decreased activity when comfort and analgesia took effect. However, activity increased in orbital frontal lobe, dorsal frontal lobe, cingulate beak and aqueductal gray matter near brainstem, which is rich in endogenous opioid receptors in the brain and is the key part of analgesia and placebo effect.
These areas of the brain are either very closely related to the brain response to pain, or are mainly closely related to psychological activities such as controlling attitudes towards these feelings and controlling emotions. Dopamine, a neurotransmitter that occurs in various psychological activities and diseases, also appears in the placebo effect.
Having said this pile of placebo/anti-placebo neurobiological mechanisms, it seems that placebo is a very powerful existence? The answer is absolutely:No!
Because the placebo effect works far more than what was discussed above.
Most of the findings just mentioned focus on situations where subjective judgments dominate, such as analgesia. In reality, although more patients with truly organic diseases may feel good about their illness, placebo has no [therapeutic] effect on those organic changes.
The top medical journals gave examples of placebo treatment for asthma in 2011. Although placebo makes patients feel [effective], it does not improve if they examine real ventilation indicators, etc. Cochrane, an organization that provides evidence-based medical evidence to clinicians, also clearly states in the corresponding documents that placebo only plays a significant role in those subjective tests.
Placebo cannot be used as a curative drug.
It is worth noting that, All studies with therapeutic purposes will definitely not give patients a placebo alone, but use it in combination with more than one drug. Patients participating in the study need not worry about taking placebo. Placebo has strong subjective evaluation effect (above), but has no effect on objective indicators (below). Quoted from < < New England Journal of Medicine > >
In conclusion, placebo itself does not produce any physiological effects, but it can induce placebo effect/anti-placebo effect, which is mainly affected by psychological and environmental factors. The positive and negative effects are manifested in human body through some neuroendocrine mechanisms.
Placebos can’t cure diseases! Placebos can also be [harmful]!