Placebos and placebo effects in gastroenterology

Speakers: Sigrid Elsenbruch (Germany), Qasim Aziz (UK)

The power of the placebo effect was first reported by Henry Beecher in 1955 in his seminal paper on the substitution of saline placebo for opiates in pain management when supplies of opiates were exhausted. Since then, the last 50 years have witnessed an explosion in the number of publications investigating the effects of both placebo and nocebo. The placebo effect arises from the patient’s expectations of treatment rather than the treatment itself. Dr Elsenbruch outlined the 3 main uses of placebo: as a tool for separating specific and non-specific treatment effects, to analyse the efferent and afferent pathways involved in psychological responses from the brain and peripheral nervous system, and in clinical practice as a treatment.

In trials of patients with irritable bowel syndrome (IBS), the placebo response varies from 33 to 88%. In one study, Dr Elsenbruch identified that 61% of IBS patients reported adequate relief of symptoms from placebo treatment with Sham acupuncture and an enhanced doctor-patient interaction: the placebo response. In a psychosocial context, the placebo response may be explained by 2 mechanisms associated with experience/conditioning and expectation. Further, rectal distension studies were performed on women who received different types of information prior to the procedure; the women were either informed that they would receive active treatment, placebo, or to expect worsening of symptoms/pain (nocebo). The results showed that, after repeated procedures the control group (informed of active treatment) got used to the experience, in the placebo group the pain rating decreased, and in the nocebo group the pain rating increased. Thus the patient’s experience of pain may be altered by influencing positive or negative expectations. Further studies identified that patients may be split into placebo responders, in whom a dose-dependent decrease in pain response could be elicited, and placebo non-responders for whom prior instruction made no difference to placebo response. In future, Dr Elsenbruch commented that it would be useful to be able to predict patients who were likely to be placebo responders.

Dr Aziz has conducted imaging studies to determine the location of the placebo centre in the brain. His research has identified that opioidergic and dopaminergic pathways and neurotransmitters are involved in the placebo response in specific areas of the brain including the anterior cingulate cortex and dorsal lateral prefrontal cortex. Interestingly, studies have demonstrated that an analgesic placebo effect experienced after dental surgery can be blocked by naloxone due to inhibition of endogenous opioids; the analgesic effect of endogenous opioids was measured to be equivalent to around 8 mg of opioid treatment. Placebo analgesia in IBS is associated with activity in the posterior cingulate cortex and insula brain regions, which differs from responses measured in control subjects. Further, there is an interaction between central, peripheral, hormonal, and immune systems in the placebo response. His studies provide evidence for activation of neuroimmune pathways and the hypothalamic-pituitary-adrenal axis during the placebo response that lead to organ-related effects.

GMFH Editing Team
GMFH Editing Team