 further evidence that the placebo effect is a genuine biological phenomenon, genetics can influence the strength of the effect. Specifically, genetic signatures that alter the opioid and dopamine signaling pathways are predictive of whether a patient is more or less likely to experience a strong placebo effect. For example, patients with opioid receptors that are less active are less likely to be placebo responders. On the other hand, patients with reduced dopamine metabolism, and therefore higher dopamine levels in the brain, are more likely to experience a strong placebo effect.
The placebo as a (not so) negative control
While placebos are grounded in a patient’s psychological reaction to receiving treatment, they can act via the same biological pathways as painkillers. In fact, placebos are so good at causing pain relief that the placebo effect is stealing the spotlight in recent clinical trials for new pain medications.
In order to be approved by the Federal Drug Administration (FDA), new drugs must prove more efficacious than placebos in clinical trials. However, in the pain field this is becoming an increasingly tall order. An analysis of 84 clinical trial results for neuropathic pain conducted since 1996 found that, while the responses to the drugs have remained about the same, the responses to the placebo have increased over the past two decades. Why might the placebo effect be growing stronger? It’s hypothesized that the increasingly showy and large-scale setting of clinical trials, combined with direct-to-consumer advertising by pharmaceutical companies, may raise patients’ expectations of drug efficacy. The result: placebo effects in pain are now so large that pharmaceutical companies have an increasingly hard time proving drug efficacy.
That being said, for most drugs the placebo effect and drug effects should be additive. In other words, a patient’s response to a drug should be equivalent to the drug’s biochemical effects plus the placebo effect. Therefore, if a drug can’t outperform a placebo in a clinical trial, it’s fair to conclude that the drug isn’t good enough to receive approval. However, when it comes to the pain field, distinguishing between placebo and drug effects can be tricky because both activate the same mechanisms, such as the release of endorphins. This means that strong placebo responses could mask drug effects in painkiller trials. Nonetheless, that doesn’t answer the question: why approve and administer a drug, which costs money and has potential side effects, when a sugar pill would have the same effect? At that point, we might as well just prescribe the placebo (or make better drugs)!
Conclusions and future directions
The placebo effect has traditionally been regarded as something negative, as a seemingly unexplained mystery at the heart of modern medicine. However, as we are beginning to understand the biological mechanisms underlying the placebo effect, it is becoming increasingly evident that placebos present a unique opportunity to harness the power of the mind in controlling pain.
The placebo effect highlights the importance of the environment in which treatment is received, and indicates that patients can benefit from language used to boost expectations. But what if there was a role for placebos themselves in medical care – what if they could be prescribed as a treatment?
Of course, this unleashes a Pandora’s box of ethical issues. The assumption is that placebos, by their very definition, must be concealed as a drug in order to work; they require deception. But maybe this doesn’t have to be the case. Doctors could prescribe placebos honestly, a so-called “open-label” placebo. Sounds like an oxymoron, right? Well, it turns out that one discussed application is to administer blister packs of painkillers that contain both the active drug and the placebo, but the patient doesn’t know which pills are which. Such pill packs might achieve the same degree of pain relief, but with less medication – thereby limiting side effects, cost, and problems with drug dependency. The next few year