Mechanism of the effect[edit]
Because the placebo response is simply the patient response that cannot be attributed to an investigational intervention, there are multiple possible components of a measured placebo effect. These components have varying relevance depending on study design and the types of observations.[34] While there is some evidence that placebo interventions can alter levels of hormones,[35] endocannabinoids[36] or endogenous opioids,[37] other prominent components include expectancy effects, regression to the mean,[26][38] and flawed research methodologies.
Expectancy and conditioning[edit]
The placebo effect is related to the perceptions and expectations of the patient; if the substance is viewed as helpful, it can heal, but, if it is viewed as harmful, it can cause negative effects, which is known as the nocebo effect. In 1985, Irving Kirsch hypothesized that placebo effects are produced by the self-fulfilling effects of response expectancies, in which the belief that one will feel different leads a person to actually feel different.[39] According to this theory, the belief that one has received an active treatment can produce the subjective changes thought to be produced by the real treatment.Â
Placebos can act similarly through classical conditioning, wherein a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus.[40] Both conditioning and expectations play a role in placebo effect,[41] and make different kinds of contribution. Conditioning has a longer-lasting effect,[42] and can affect earlier stages of information processing.[43] Those that think that a treatment will work display a stronger placebo effect than those that do not, as evidenced by a study of acupuncture.[44][45]
A placebo presented as a stimulant will have this effect on heart rhythm and blood pressure, but when administered as a depressant, the opposite effect.[46] Perceived ergogenic aids can increase endurance,[47] speed[48] and weight-lifting ability,[49] leading to the question of whether placebos should be allowed in sport competition.[50] In addition, there are ethical and moral concerns related to their use and we must be cautious of policies and practices that exploit placebos to the detriment of athletes’ health and well-being.[51]
Because placebos are dependent upon perception and expectation, various factors that change the perception can increase the magnitude of the placebo response. For example, studies have found that the color and size of the placebo pill makes a difference, with "hot-colored" pills working better as stimulants while "cool-colored" pills work better as depressants. Capsules rather than tablets seem to be more effective, and size can make a difference.[52] One researcher has found that big pills increase the effect[53] while another has argued that the effect is dependent upon cultural background.[54]
Motivation may contribute to the placebo effect. The active goals of an individual changes their somatic experience by altering the detection and interpretation of expectation-congruent symptoms, and by changing the behavioral strategies a person pursues.[55][56] Motivation may link to the meaning through which people experience illness and treatment. Such meaning is derived from the culture in which they live and which informs them about the nature of illness and how it responds to treatment. Research into the placebo treatment of gastric and duodenal ulcers shows that this varies widely with society.[24] The placebo effect in treating gastric ulcers is low in Brazil, higher in northern Europe (Denmark, Netherlands), and extremely high in Germany. However, the placebo effect in treating hypertension is lower in Germany than elsewhere.[57]