Gabor Szendi:
About the placebo effect, from a slightly different angle

The placebo is a good acquaintance to make. It lives in the public consciousness, and the concept of a placebo effect is used mostly when someone is healed through a treatment that we suspect is in fact ineffective. However, things are rather more complicated than that.

 

 

The British Medical Journal has summarized the results of 3,000 clinical trials on its Clinical Evidence website. According to this, only 11% of the therapies used today have proven efficacy, and at least 65% have no proven efficacy, or the therapy is even clearly harmful (CE, 2017). The placebo effect is the reason why this cannot be clear in daily practice. If everyone's status were to deteriorate, or even if a condition would simply not improve with treatments that have not been proven to be effective or harmful, that would quickly become apparent. Knowing the many tricks of the pharmaceutical industry fraudsters, 11% "proven effective" is also questionable. In other words, while constantly striving to be scientific and rational, medicine works with placebos as a main effect, in the same way as the natural medicines that it looks down on.

To give just one example, what is meant by "proven" medicine? In clinical trials, patients must be informed about risks and side-effects, and that they could even be put into a placebo group. Everyone knows that a placebo is a harmless substance that has no side effects, for example, properly encapsulated glucose. And everyone signs up to the study because they want to be healed. That is, they want to be in the group receiving the active substance. So patients do their best to find out if they are receiving an active substance or a placebo. For example, they will chew the tablet or open the capsule.

The clinicians themselves realize which group the patient belongs to from side effects, and unintentionally betray their suspicions. So there is the placebo effect, which comes from the patient starting a hopeful treatment, and an extra effect called the active placebo effect. This is because the patient infers from the side effects which group they were put into. It is a common experience that the more unpleasant the side effects of a drug are, the more effective it will be. If the pharmaceutical industry wanted protection against this active placebo effect, it would use a placebo that has similar side effects to the drug being tested. But the pharmaceutical industry is no enemy to itself, and an active placebo is not used. When, for example, an active placebo was used in antidepressant trials, a zero drug effect was the result, demonstrating that antidepressants have only a placebo effect (Moncrieff, et al. 2004). Everyone learned from this.

The placebo effect has an opposite, the nocebo effect, which is when some objectively harmless treatment has an actual detrimental effect. A good example of the nocebo effect is that after a cancer diagnosis, in the following week cardiovascular mortality increased 5.6 times compared to the population average, according to one study (Fang et al., 2012). It's important to emphasize this because placebo and nocebo effects are much more woven into our daily lives than we might think.

About the body's self-healing ability

Nowadays our innate and acquired immunity handles most pathogens without us even knowing it, but only a single bacterium or virus can knock us off our feet spectacularly. It is also natural that injuries and fractures heal on their own, and after brain injury - with adequate practice of course - lost functions can be regained. It is less common, but people can even heal from different types of cancers without medical treatment (Chang, 2000). At least a thousand cases are known in the literature, and a number of undocumented cases can be significant as well. The most famous is the case of St. Peregrinus, who lived in the 13th century and had such a large tumor on his lower leg that doctors decided to amputate the leg. However after a night of prayer, the tumor disappeared, and never returned (Chang, 2000). Some spontaneous healings occur as a result of the patient receiving a serious infection, and the immune function treats the cancer as a "subsidiary". But in many cases, unsuccessful surgical intervention or diagnostic sampling causes the patient to believe that they have been "cured," and they heal accordingly.

"Real" and placebo cures are often inseparable. It is known from animal experiments that virtually any physiological and immunological response can be conditioned. For example, if a rat is given insulin a few times, and its blood sugar level gets lower every time, then distillated water will also cause the lowering of blood sugar level. Thus, anyone who has already taken medication is practically conditioned to the drug-induced effect. Even if asthmatics are given a bronchoconstrictor instead of the usual bronchodilator spray, the inhaled spray will still have a positive effect. Nausea can also be decreased by a nausea-causing agent. I could list a thousand examples: the point is that pills and injections have a magical effect. The color, shape, number of tablets, how often they should be taken, and the impulse they give all determine - and sometimes only these attributes determine - the effect of the tablet. The remarkable pain relief effect of administered saline solution was the same as that of 8 mg of morphine (Levine and Gordon, 1984). There are also studies by Fabrizio Benedetti where patients were given medicine in a hidden way to measure the objective effect. The method was simple: an automated machine started and stopped the drug administration in an infusion-bound patient, and the patient or a nurse constantly logged the various physiological and psychological parameters. Painkillers administered in secret were shown to perform significantly more poorly (50% more had to be added to achieve the same effect), and Seduxen was ineffective in reducing anxiety when administered covertly.

One possible treatment for Parkinson's disease is electrical stimulation with electrodes implanted in the brain. The effect of this treatment is much greater if the patient is aware, than when it is applied in a secret manner (Benedetti et al., 2011). The phenomenon of placebo surgery is also well known. In the 1950s, surgery was regularly performed under the influence of a false anatomical assumption, where the internal breast artery was strangulated because it was believed to improve blood flow to the heart. Objectively measured, patients tolerated exercise better, until it was shown that it was only a placebo effect by a placebo controlled study (with only a skin incision in the placebo group). Laser therapy which was supposed to stimulate the formation of new blood vessels by burning holes in the heart, met the same fate. In Parkinson's patients, the effects of stem cells implanted in the brain were compared with those of sham surgery on the head only, which showed a spectacular improvement in movement in the placebo group as well. Hundreds of thousands of knee surgeries a year have also shown that pain decreases only because of the effects of placebo (Szendi, 2005).

To give you an example of nocebo as well, missed or discontinued treatments often lead to deterioration through the nocebo effect. Notable nocebo effects have been described in China. Those who suffer from a disease described by their horoscope die years before those who suffer from the same disease, without their horoscope indicating it. In Chinese culture, the number 4 is sinister, and more people die in hospitals on the fourth day of the month than on other days. Monograms can also have both placebo and nocebo effects. Having two first names is common for Americans, and for some people their monograms have positive meaning (GOD, VIP), while others sound unfortunate (PIG, BAD). People with positive sounding monograms live longer on average than those whose monograms possess negative meaning (Szendi, 2017).

These conditioned responses work in animals as well as in humans. In another type of placebo/nocebo response - let's say a superior one - just the expectation produces an effect. Expectations develop in the prefrontal lobe, so for example, Alzheimer's patients or people with intellectual disabilities do not have this type of effect, so for example there is no difference in the effect of lidocaine administered either secretly or openly (Benedetti et al., 2011). Placebo research nowadays overemphasizes the role of consciousness. However recent studies indicate that a placebo effect may develop even if the patient knows they are receiving a placebo (Kaptchuk et al., 2010; Carvalho et al., 2017). Again, we are confronted by the fact that our brains, in a sense, work independently of us.

The roots of the placebo response

Homeopaths often claim that there is no placebo effect in animals, and yet they still heal. Both sides, homeopathy advocates and attackers, should know that animals do have a placebo response as well. I could even say that if humans would not have it, then animals would not either. The "expectation" of the non-conditioned type of placebo effect exists in animals in the same way. Humans are different in this respect from animals only in that they can make themselves aware, and the expectation may be more efficient and multifaceted in humans, due to the many effects of verbalism and culture.

In horses, there is a nervous system disorder which causes involuntary head shaking. All kinds of nutritional tricks have been common to treat this, but one study found all of them ineffective, but showed a serious placebo effect (Talbot et al., 2013).
Dogs are usually afraid of fireworks. When homeopathic remedies that were considered effective and a placebo were administered to easily-scared dogs, the homeopathic medicine did not prove to be more effective than the placebo, but there was a 45% improvement in both groups, and 10% of the dogs became asymptomatic (Cracknell et al, 2008).
Three placebo-controlled drug trials have also been conducted to treat epilepsy in dogs. In the placebo groups of the three studies, there was a 26%, 29% and 40% reduction in the number of seizures (Munana et al., 2010).
Dogs with arthritis were treated with nonsteroidal anti-inflammatory drugs. The drug was more effective than the placebo, but 19 of the 34 dogs receiving the placebo showed improvement (Vasseur et al., 1995).

It can be shown that in animals living with humans, they understand their master's hidden expectations and metacommunication signals. Clever Hans, the famous performing horse, answered to the questions asked with hoof clattering, or by selecting letters. It turned out that he only "knew" the answer to questions which the questioner knew as well. The horse sensed during his clattering of hooves, when the questioner became relieved after the correct number of clatters was reached, and then stopped (Bondeson, 2013). Animals are much more sensitive to smells, hidden movements, and sounds than we humans are, and sense the expectations of the caretaker or master, to develop a placebo response.

An 'expectation' develops in animals in the wild as well. Animals who live in a hierarchy conceal their disease by "pretending" to be healthy. Animals also think in sensory-movement patterns, that is, when they want to go hunting, despite the animal's weakness, they imagine an "expectation" against the real situation.

If we call the phenomenon from wound-healing through the immune system that responds to an infection, a combined self-healing ability in which the organism is able to heal itself through various mechanisms, then the placebo effect is not so mysterious after all. For hundreds of millions of years, as the animal world evolved, the ability to self-heal was a major breeding advantage. So natural selection made it possible for more successfully self-healing animals to spread. However, in the case of a placebo response, the question arises as to why a stimulus is needed to trigger it, whether it is a decision to heal, a treatment, or even the sight of others healing at places of pilgrimage. The question is more complex than having an absolutely convincing answer in one sentence. However healing is not always timely. It is no coincidence that relaxation promotes healing, as the active fighting of the immune system, for example, requires a lot of energy, and this energy is often much better used for survival during fighting, escaping, or psychological stress, than during healing. Thus the phenomenon of timed healing (and illness) serves survival. The stimulus, situation, and information that can trigger the placebo effect can be called "permitting" for healing (Humphrey, 2002). Remember, hopelessness caused by untreatability or incurability is a nocebo effect: it creates the expectation that the problem cannot be overcome in any way. "Permitting" somehow gives new hope that stimulates the body to increase self-healing.
The reason why not everyone is capable of doing this is because placebo sensitivity is a hereditary trait, just like the strength of the immune system (Hall et al, 2015).

 

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