The placebo effect can have a major impact on treatment outcomes. Although much remains unknown about how and why patient expectations affect the effectiveness of drugs and treatments, we know this to be true. “There is ample evidence that the placebo effect in general, and placebo analgesia in particular, is not simply a ‘psychological’ effect, but is underpinned by complex neurobiological phenomena,” says Ulrike Bingel, co-author of the new paper. paper In a paper published in the journal PLoS Biology on September 24th, Popular Science.
These neurobiological phenomena remain the subject of active research. One proposed explanation is that the expectation that a treatment will be effective activates the brain’s mesolimbic pathway, a system that provides a sense of motivation to perform a behavior and a sense of reward and satisfaction when the behavior is performed. This system relies on the neurotransmitter dopamine, and the experiments documented by Bingel and his team in their paper tested the hypothesis that dopamine-based reward and learning mechanisms contribute to the placebo effect.
[ Related: In painkiller trials, placebo effect is becoming more powerful ]
Specifically, the researchers studied how dopamine levels in the brain affect the effectiveness of placebo analgesia (i.e. placebo pain relief). To conduct the study, participants were split into two groups. One group was given a dopamine agonist drug beforehand, suppressing dopamine levels in the brain. The other group was given L-dopa, a precursor to dopamine, effectively increasing dopamine levels. Each group was then subjected to a painful heat stimulus and given an identical placebo painkiller. Surprisingly, the team found that the effectiveness of placebo analgesia did not depend on the participants’ dopamine levels.
This suggests that ambient dopamine levels in the brain don’t influence the strength of the placebo effect. But given that dopamine is important for the brain’s reward pathways, the apparent lack of dopamine influence on placebo analgesia also raises the question of how these pathways are involved in the phenomenon. Bingel points out that this is not a question the study directly addressed: “We can only talk about the neurotransmitter dopamine, but nothing about clear neurobiological mechanisms.” [reward] “We haven’t done any brain imaging, so we don’t know the circuitry,” she said. “But we do know,” she said.[Dopaminergic] The pathways are very well described and, based on the evidence to date, it is reasonable to at least speculate about their involvement.”
The situation with painkillers is complicated by the fact that dopamine is also involved in the actual phenomenon of pain relief. “Any pain relief is inherently rewarding,” agrees Bingel. “So, [it] “It’s likely that the dopamine pathway is involved,” she says. This is because dopamine teeth Involved in placebo analgesia: “Our study shows that the involvement of this dopamine pathway is not causally involved in the analgesic portion. It may be an epiphenomenon,” that is, a secondary phenomenon that arises from and is associated with a primary cause.
Although common parlance tends to refer to the “placebo effect” as a single phenomenon, scientists tend to view the various placebo-related effects as separate phenomena that share a common neurobiological basis. “This neurobiological basis is not limited to placebo analgesia,” explains Bingel. “It is recognized in many placebo effects, but placebo analgesia is probably the best studied to date.”
But where the common basis ends and the individual effects begin remains an open question: To what extent, for example, does a placebo for pain work similarly to a placebo for depression?
“That’s a great question,” says Bingel. “It’s possible that there are overlapping brain networks responsible for the placebo effect, particularly when it comes to pain and depression. But so far, the two mechanisms are not well understood. [have not been] “We will do a direct comparison. We hope that within the next few years we will understand the shared and distinct neural circuits underlying the placebo effect in pain and negative affect/depression.”
Another variable here is that the placebo effect essentially depends on the patient’s expectation of a positive outcome. Strength Bingel points out that patients’ desire for a positive outcome is relatively low in a research context. After all, participants voluntarily took part in the study, and the pain they experienced was relatively mild. “In our study, participants were only passively administered painkillers, and we can assume that motivation/desire for pain relief is low in this highly controlled experimental situation with healthy volunteers.”
Obviously, the situation is very different for people who actually experience chronic pain and crave relief from it, and Bingel says that in those cases, reward pathways may play a different role. “While our findings make it highly unlikely that dopamine is the cause in this particular situation, we do not exclude the possibility that dopamine may play a role in different motivational situations (such as might be expected in patients suffering from chronic pain) or when treatment involves more ‘active control’ or ‘agency.'”
There are many subtleties to how the placebo phenomenon works, so it’s not surprising that the subject remains a subject of active research. Bingel says a deeper understanding of how the placebo effect works is important for incorporating it into treatments: “Tomorrow’s pharmacological strategies will need to exploit the valuable interplay between endogenous pharmacology (notable in the placebo effect) and specific medical procedures such as drug treatments.” [But] To systematically target the placebo effect, we need to understand its mechanisms.”
