The placebo effect remains as the most bizarre aspect of modern medicine. The placebo effect occurs when a patient is led to believe that they are receiving a medically effective treatment, when in fact they are receiving none. The most influential studies investigating the placebo effect usually involve sugar pills or ‘dummy pills’, the purpose of which is to convince the patient that they are taking a pill with medicinal properties. Strangely enough, even though the pill has no chemicals that could have a physiological effect on the body, physiological effects still take place, often with curative results.
The placebo effect is believed to work based on the psychosomatic model in medicine, which teaches us that – due to the intimate relationship that exists between the mind and body – mental processes can affect medical outcomes. Precisely how culture, meaning and belief can allow us to recover from illness is still shrouded in uncertainty. For example, what brain processes take place when we believe that we will get better? Nonetheless, some progress has been made in our understanding of this miraculous effect. In order to appreciate the incredible strangeness of the placebo effect, consider the following.
What We Know About the Placebo Effect
For people with mild depression, placebos work just as well as anti-depressants. This has been confirmed by many studies. (In severely depressed patients, however, anti-depressants are more effective than sugar pills). A study titled Commercial Features of Placebo and Therapeutic Efficacy shows that expensive placebos are more effective than less expensive placebos. A study from 1981 published in the British Medical Journal found that the particular brand attributed to a dummy pill – its labelling and marketing – could change the analgesic (pain relieving) effects of that pill in the case of headaches. The more popular and trusted brand had greater pain-relieving effects, even though the pill contained no active chemical properties.
The placebo effect has been shown to have a dose-response relationship, meaning that the higher the dose, the more effective the treatment, just as in ‘real’ medicine. In other words, two placebos are better than one. There is some evidence to support this claim, although it has not been determined by other studies as of yet. The more dramatic ways of administering a placebo are more efficacious than the less dramatic ways, meaning that injections work better than pills and a consultation session with a doctor before administrating the pill is more effective than just administrating the pill. Taking the pill in a hospital will also be more effective than taking it anywhere else.
The power of the placebo effect is not a relatively new discovery either. This study from 1949 found that the placebo effect is so powerful that it can overcome real pharmacological effects. In the study, participants who were given a drug designed to induce nausea didn’t develop such symptoms because they were told that the drug would relieve nausea. This seems to be one of the most fascinating examples of ‘mind over matter’.
It is widely believed that the placebo effect relies on the doctor deceiving the patient, i.e. telling them that what they are taking is medicine when it isn’t. However, In this study published in PLOS ONE, the researchers found that a placebo effect could be induced in patients with irritable bowel syndrome (IBS) even when they were told they were taking placebo pills (albeit with the caveat that this had been shown to help patients in the past with IBS). However, a more recent study demonstrated that a placebo works even you know it’s a placebo.
The colour of the pill can also be significant. In a study titled Demonstration to Medical Students of Placebo Responses and Non-Drug Factors, students were told that they would receive a pill with either sedating or stimulating effects. Students who took the blue pill (a placebo) were convinced it had sedating effects, while those who took the pink pill (also a placebo) were convinced it had stimulating effects. Because we associate blue with calmness and pink or red with stimulation, these cultural factors affected the outcome of the experiment. Certain colours can boost the efficacy of a placebo in relation to gender as well.
The pharmaceutical company Eli Lilly, for example, repackaged fluoxetine (Prozac) as Sarafem and the only difference between the drugs was that Sarafem came in pink and lavender colours. It still contained fluoxetine, which is an antidepressant. Eli Lilly knew about the placebo effect and believed that the pink colour of Sarafem would be more effective in treating premenstrual dysphoric disorder (PMDD). (PMDD was a disorder introduced in 1994 by the American Psychiatric Association (APA) which in effect medicalised the menstrual cycle.)
It Gets Stranger
The placebo effect gets even more surprising than this. All of the previous studies mentioned rely on the assumption that the placebo works because the patient is conscious that they are receiving some form of treatment. However, a study published in PNAS discovered that the unconscious mind plays a key role in the placebo effect. The researchers found that the placebo and nocebo effect (a detrimental effect on health caused by a ‘dummy pill’ or ‘dummy treatment’) could be activated even if the patient had no expectation of getting better or worse. As study co-author Ted Kaptchuk notes:
It’s not what patients think will happen [that influences outcomes] it’s what the nonconscious mind anticipates despite any conscious thoughts. This mechanism is automatic, fast and powerful, and does not depend on deliberation and judgment. These findings open an entirely new door towards understanding placebos and the ritual of medicine.
Culture, Belief and Meaning
The three mechanisms by which the placebo (or nocebo) effect operates: culture, meaning and belief. In every culture, no matter what time and place we are referring to, there was always been someone designated as the ‘healer’. In indigenous cultures, these healers are often referred to as the ‘medicine man/woman’ or ‘shaman’. In modern industrialised societies, we refer to these designated people as ‘doctors’, ‘therapists’, ‘surgeons’ etc. Deeply embedded in every culture then is the assumption that these people are experts who have been trained to cure us. Thus, the belief that these people will cure us is what contributes to our recovery from illness.
Also embedded in our culture is the assumption that these experts possess almost magical potions which can make us better. In more traditional societies, these potions can take the form of herbs with no known medicinal properties or herbs with psychoactive properties, but with no known medicinal properties. Yet both can induce placebo effects. This could explain why some people (such as former shaman turned artist Pablo Amaringo) who drink ayahuasca in the Amazon may report alleviation from a medical problem. The expectation that the brew will have such an effect, the context of the ceremony, and the experience itself may contribute to this seemingly miraculous effect.
In regards to the study examining the relationship of the unconscious mind to the placebo effect, shamanism may be relevant here as well. After all, if shamanism is as old as some academics claim (13,000 years old or even older) then perhaps the notion of the ‘healer’ is deeply ingrained in our unconscious mind. The Swiss psychotherapist Carl Jung argued that archetypes (universal images) reside within our unconscious mind and are inherited, not learnt. Some of these archetypes include the Mother, Father, Wise Old Man, Trickster – universal characters which we find again and again in myths from all over the world. Perhaps the Shaman or Healer is another one of these archetypes. Therefore, as soon as we recognise this person in real life (based on where they work, what they wear, how they speak, their facial expressions and gestures, what tools and substances they use) then our unconscious mind can react to this in the form of a placebo effect. Although this is just speculation.
The placebo effect also works because of the meaning that we attach to certain things. As shown in the studies above, a red pill is more effective as a stimulant because we immediately attach the notion of ‘stimulation’ to the colour red. Likewise, a blue pill is more effective as a stimulant because we immediately attach the notion of ‘calmness’ to the colour blue. Humans, therefore, have this extraordinary power which animals don’t have – our ability to inject the world with meaning allows us to recover from an adverse situation in a way that animals cannot. Belief is the last mechanism by which the placebo operates. The belief or expectation that you will get better plays a key role in recovery. With the nocebo effect, if you expect to get worse when taking a dummy pill then you are more likely to get worse than if you think more positively about the situation.
What’s Going On in the Brain?
So we have some bizarre studies of the placebo effect and the mechanisms by which it can work, but what brain processes are involved in the placebo effect? In other words, how does our brain manage to make us better even when we have taken something with no pharmacological effects? A study published in the Journal of Neuroscience revealed that the placebo effect is related to endorphins, the brain’s own natural pain relievers. The subjects in the study had their brains scanned by a PET scanner while being given a painful but harmless injection. The subjects were then told that they would be given a pain reliever, whereas it was actually a placebo. Interestingly, the scan showed a change in brain activity in the opioid receptors (which receive endorphins) and the brain areas relating to processing and responding to pain.
Professor Ted Kaptchuk, a professor of medicine at Harvard Medical School, commented: “The ritual of medicine activates particular areas in the brain that actually will reduce pain, or at least reduce the sensations that we have in relation to pain.” He even claimed that placebos could rival active medication in the treatment of asthma.
We understand how the placebo works, in part, due to endorphins and pain receptors in the brain. But much more of the mystery remains to be unravelled. Of course, there is also an ethical dilemma facing the medical community. Can placebos be introduced as standard practice and treatment in medicine? Are doctors not morally obligated to be completely honest with their patients about the treatment they’re receiving? Patients should be able to trust their doctors, so if they attempt to deceive their patients in any way, by using placebos, then this might erode the integrity of the doctor-patient relationship.
On the other hand, the benefits of placebos include the fact that they are inexpensive, save time, lack side effects, and they eradicate the possibility of dependency or overdose. There are many papers which take into consideration the ethical issues surrounding placebos, whilst concluding that they can still have a legitimate place in medicine. Here is one paper, titled The Ethics of the Placebo in Clinical Practice, which examines this issue. After all, placebos can be administered without deception.
Mood disorders like mild depression (but also mild hypertension, mild diabetes, headaches) are influenced by non-specific factors like regression to the mean, inherent symptom cyclicality and homeostasis, somatic load, seasonality, personality, expectation, attribution bias, informed consent symptom suggestion and the extra professional attention of the clinical trial testing milieu (i.e. tribal-social cohesion factors). I agree it should be (and usually is) carefully controlled for in pharmaceutical trials; it is not easy to control for it ethically in many costly and potentially risky surgical interventions that may have little clinical benefit; acupuncture studies are often not controlled adequately by double-blind sham procedures; lastly, usually small placebo effects would require very large sampling groups to be adequately powered to identify their presence…who is paying the bill and the IRB to test these sugar pills robustly ?…paired dogs may also have “placebo like non-specific effects” if one is injured and is preferentially treated by the feeder/caretaker, the healthy member will develop limping and respond favorably to non-specific “treatment” and care…I agree it is unethical to treat animals only with homeopathic substances without evidence-based specific benefits…I also think the distinction between “non-specific” and “specific” benefits of a treatment in a diverse, randomized, and double blinded test population is a better goal than studying the “murky world” of placebo effects…often an epiphenomenon of poor study design and inadequate powering…where the investigator himself becomes the “limping hopeful dog” seeking justification for publication…it’s not what we don’t know…it’s what we think we know for sure that gets us most in trouble.