In most cases, in the scientific literature, or in popular culture, a placebo effect is defined as the patients response to an inert substance (a substance without an intrinsic effect). But this definition is a paradox. How can a inert substance, that does not cause any effect, still have an influence on the health status of the patient? Magic or power of the mind?
To clarify and demystify this assumption, we added in treatment equations another variable, namely the psychosocial context in which it is conducted. The effect produced by administering a placebo can not be attributed to inert substances since saline or sugar tablets will never have therapeutic properties, but the context in which therapy is conducted is important in this equation. In the studies that analyse the placebo effect, values and beliefs shape how neural processes related to perception, emotion, physical and mental state of the patient (1).
It is important to note that the placebo effect is a neurobiological response, that has an identifiable physiological substrate. In short, taking inert powders have a physiological response. Psycho-social factors include aspects such as verbal suggestions, behavior and language of the medical personnel or other persons involved in the therapy, and elements like hope that create a positive or negative result in the patients therapy.
Sometimes, other phenomena are confused with placebo, and this has given a negative image to the issue. To see a true placebo effect, scientists performed clinical studies and analyzed responses to different types of treatment of several groups of people. The placebo effect allow researchers to approach the relationship between mind and physiological response to treatment, since they can study how certain psychological phenomena such as hope, memory or emotions can produce changes in human brain, changes that can lead to the improvement of health.
The bigger the placebo pill, the stronger the effect
The placebo effect is a psycho-biological phenomenon, which can be attributed to various mechanisms, depending on the context in which it is studied. In other words, the placebo response may depend either type of emotions such as anxiety or hope or on certain neuro-transmitters (dopamine in Parkinson’s disease) or can be genetically influenced, because of different variants of genes. The detailed procedures have been described for analgesia and Parkinson’s disease.
Regardless the influences color, shape or size of the placebo pill has, the therapeutic outcome or if the placebo effect can produce addiction and how this effect varies according to geographical area and population, you can find a short interesting video below.
Pain, analgesia, opioids
When pain occurs, our brain secretes endogenous opioids (endorphins) that act on specific receptors in the brain, called opioid receptors (the same receptors that morphine acts on) and pain subsides.
The neurobiology of the placebo effect was first described in 1978, following a study in which it was proved that naloxone, an opioid antagonist (stops the action of opioids) could block the effects of placebo in analgesia (2). In other words, treatment with placebo induced secretion of endogenous opioids has led to the reduction of pain and naloxone blocked the analgesic effects of the placebo.
The decrease in pain in the body can be carried out through mechanisms that depend on opioids as well as through non-opioidic pathways. In an experimental model of pain, the placebo response could be blocked by naloxone if patients were convinced that the placebo drug was a very good painkiller (if patient expectations were low, placebos had no effect and naloxone wasn’t effective either). Such studies demonstrate the importance of psycho-social context when treating with placebos in parcitular and with any other drug in general. Opioids such as morphine have side effect, such as respiratory depression. If the patient was treated with an opioid, and later was given a placebo, it was observed that respiratory depression occurred in both cases. What’s more interesting is that in this case respiratory depression could be blocked by naloxone in both groups of patients. This shows that the systems are not simply acting opioid on pain receptors, but also on the opioid receptors responsible for the respiratory effects.
The placebo effect is a phenomenon that can be learned both conscious and unconscious. In scientific literature, studies show that placebo responses are mediated by conditioning when unconscious physiological functions are involved (such as hormonal secretions) and are also mediated by hope when conscious processes are involved, such as pain and motor performance. Conditioning appears to be important for immunological mechanisms. In a related study in which cyclosporin A (immunosuppressant) was administered concomitantly with a flavored beverage, after repeated administration, it was observed that even administering only the beverage flavor can induce immunosuppression in patients. Such requirements can be obtained in the case of growth hormones or cortisol.
Expectation (hope) nocebo
Expectation plays an important evolutionary role in preparing the body to anticipate certain events to be able to adapt more easily. There are several mechanisms through which expectation can affect physiological functions. For example, the expectation of a positive event may reduce anxiety or activate neural reward mechanisms (3).
We define the placebo effect as the one that induces a positive response. His evil twin brother, nocebo has a negative influence on therapy. To induce a type of nocebo response, the patient is given an inert substance, accompanied by negative verbal suggestions related to clinical worsening or exacerbation possibilities for side effects to the treatment. Therefore, the patient becomes anxious and negative expectations can produce changes in his brain which can result in increased pain.
Why is this effect?
If our body has the ability to heal itself following administration of a placebo, why can’t we have a spontaneous healing, without administering a placebo?
Professor Nicholas Humphrey explores this hypothesis of an evolutionary perspective and examines the relationship between the benefits and risks of pain:
What about real drugs?
Remember that the placebo effect depends very much on the context of psychosocial of treatment, and it can have a significant influence on the outcome of the treatment, but in many cases it is not a substitute for classic therapy.
Take the case of anti-depressants. We investigate if their therapeutic effect exceeds or not the effect of placebo pills. Although it is possible that both treatments have similar results in the short term, there are studies showing that relapse of depression is much more increased in patients treated with placebo. Why? It was shown that after treatment with anti-depressants, a certain protein called BDNF (Brain Derived neurotrophic factor) is produced in greater quantity. This protein is important in the development and differentiation of neurons, which leads to a therapeutic response in long term treatments, effect that the placebo lacks.
The effects of placebos / nocebo will be extensively studied further, not just because they can prove to be powerful tools for treating chronic diseases but also because the fascinating manner in which they can stimulate one of the most powerful weapons in our arsenal, the human brain.
Reading an article on the Internet cannot replace years of experience in the medical field and is never considered exhaustive. For further information regarding the placebo effect and advice on how to live a smarter and healthier life contact the pharmacists!
This article is written by Alexandra Prodan. Alexandra is a student at the Faculty of Pharmacy of Cluj-Napoca and she is passionate in neurosciences. We hope to share more of Alexandras work on www.farmacist.info since we have much to learn about this exciting field and the mysteries of the mind. If you like the subject, give a share and leave a like!
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