Drug side effects may not always be a bad thing, for painkillers at least. An inert nasal spray that was presented as having painkilling properties was deemed more effective when it caused a mild burning sensation, suggesting that this boosted the placebo effect.
The placebo effect is when people experience a medical benefit from the belief that they have had some kind of healthcare intervention, even when they haven’t actually received it. The mechanism behind the effect is unclear.
The results suggest that a drug’s side effects could potentially be used to enhance its benefits, but these could also make medicines being tested in placebo-controlled randomised trials seem better than they really are, say the researchers.
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Drug trials often compare people who receive a particular medicine to those who are given an identical-looking version of the treatment that contains no active ingredient. But these assume that people can’t tell the difference between the real drug and the placebo version.
at the University Medical Center Hamburg-Eppendorf in Germany and his colleagues wondered whether a drug’s side effects might sometimes indicate to research participants that they received the real medicine, enhancing any placebo effect.
To find out, they asked 77 volunteers to test a nasal spray containing the painkiller fentanyl before having a heated object applied to their skin. Then they were asked to rate their pain from 0 to 100.
The participants were told they would have three tests, which could involve the real painkilling spray or a placebo version of it. In fact, none of the sprays contained fentanyl, but some had a small dose of capsaicin to induce a burning sensation, fooling the participants into thinking they had received fentanyl and were experiencing a side effect.
The pain caused by the heat on the participants’ skin was rated as more intense when people got the inert spray than when they had the capsaicin spray – with a score of about 30 compared with about 25. This difference disappeared in a subsequent test in which people were told there was no fentanyl in any of the sprays, suggesting that the effect wasn’t due to people being distracted by the sensation in their nose, for example.
“Our data suggest that mild and benign side effects do not necessarily have to be harmful to patients and could potentially even resemble an overall benefit for treatment outcomes,” the researchers write in their paper. “One could even think of artificially changing the formulation of established drugs to include mild side effects, to increase treatment expectations.”
at the University of Manchester, UK, says the results fit with what we know about the placebo effect. “Pain is a very unfixed sensation,” he says. “What you experience is a combination of the sensory stimulation and what you’re expecting to experience.”
Jones says the results would have been more convincing if the team had induced a side effect other than pain, as sometimes one sort of pain signal can inhibit the processing of a second sort of pain.
Nevertheless, the results suggest that some drug trials may have overestimated the effect of certain medicines because people could guess whether they had been given the real drug or the placebo version due to the presence or absence of side effects, says Jones.
This is a concern in trials of psychedelic drugs, such as those made from the chemical responsible for the effects of magic mushrooms, where it is often easy for people to guess if they are receiving the real medicine or a placebo pill.
MedRxiv
