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]
Though the placebo effect is typically associated with deception in order to invoke positive expectations, studies carried out by Harvard Medical School have suggested that placebos can work even without deception. In an attempt to implement placebos honestly, 80 patients suffering from IBS were divided into two groups, one of which receiving no treatment, while the other were provided with placebo pills. Though it was made clear the pills had no active ingredient, patients still reported adequate symptom relief.[58] Another similar study, in which patients suffering from migraines were given pills clearly labeled placebo, but still reported improvements of their symptoms.[59]
Placebo effect and the brain[edit]
Functional imaging upon placebo analgesia shows that it links to the activation, and increased functional correlation between this activation, in the anterior cingulate, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, the brain stem periaqueductal gray matter,[60][61][62] and the spinal cord.[63][64][65][66]
The higher brain works by regulating sub-cortical processes. High placebo responses link with enhanced dopamine and mu-opioid activity in the circuitry for reward responses and motivated behavior of the nucleus accumbent, and, on the converse, anti-analgesic nocebo responses were associated with deactivation in this part of the brain of dopamine and opioid release.[61] (It has been known that placebo analgesia depends upon the release in the brain of endogenous opioids since 1978.[67]) Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray[61] on spinal nociceptive reflexes, while the expectations of anti-analgesic nocebo acts in the opposite way to block this.[63]
The brain is also involved in less-studied ways upon non-analgesic placebo effects:
• Parkinson's disease: Placebo relief is associated with the release of dopamine in the brain.[68]
• Depression: Placebos reducing depression affect many of the same areas that are activated by antidepressants with the addition of the prefrontal cortex[69][70]
• Caffeine: Placebo-caffeinated coffee causes an increase in bilateral dopamine release in the thalamus.[71]
• Glucose: The expectation of an intravenous injection of glucose increases the release of dopamine in the basal ganglia of men (but not women).[72]
• Methylphenidate: The expectation of intravenous injection of this drug in inexperienced drug users increased the release of dopamine in the ventral cingulate gyrus and nucleus accumbens, with this effect being largest in those with no prior experience of the drug.[73]