The placebo effect is a strange and still not entirely understood quirk of medicine. On the face of it, someone's health should not improve if they are given a simple sugar pill instead of a tablet carrying a drug. But sometimes it does.
It is just about possible to imagine that the placebo effect stems from a strong faith in the power of doctors to cure us. If that is the case, then the effect would be limited to our species – after all, animals do not really put their faith in veterinarians when they are sick. And, indeed, many scientists assume placebo effects are not seen in animals.
But not all scientists do. Some say there is evidence that placebo effects can and do play out in our pets.
It is not actually that uncommon to use placebos in animals. When a new animal therapy is on trial, scientists often test it using a similar procedure for evaluating human therapies. They give some animals the therapy and others a placebo, so they can fully assess the potency of a new therapy.
Some say there is evidence that placebo effects can and do play out in our pets
"Initially we sought out to use the placebo just as a baseline," says Karen Muñana, a neurologist at the North Carolina State University College of Veterinary Medicine in the US, who studies epilepsy in dogs.
"But then in the evaluation of that data we realised that the dogs that had been on placebo had shown improvement in their seizure frequency compared to before we started the study," she says. "Their seizure frequency went down."
The data suggested that the dogs on placebo treatments were doing better than they had been doing before the trial. Their condition was improving even in the absence of medicine. They seemed to be displaying a placebo effect.
Why would this be the case? Muñana thinks that several factors could be at play.
One of the most obvious – but often overlooked – factors is that disease naturally changes in an animal over time.
"Epilepsy is a waxing and waning disease with a natural course," says Muñana. "What happens in epilepsy is that owners will seek care when their dog's disease – when their seizures in this case – are at the worst."
If anything, it is the pet owner who might be responding to the placebo
This means it is possible that the dogs in Muñana's epilepsy trial were experiencing particularly intense symptoms as the trial began. Even if they had not been put in the trial, their condition might have improved naturally over the course of a few weeks. If this is the explanation for the trial results, then the dogs were not really experiencing a placebo effect.
But this is not the only possible explanation. Just the effect of knowing that their animal is taking part in a drug trial can change the behaviour of a dog owner, says Muñana.
"The owner's perception [is] that the dog is being monitored better, watched better," she says. "Perhaps because they're in the study [the owner is] more likely to give those medications that are being used to treat the underlying disease."
Again, this would imply the animal itself is not experiencing a placebo effect. If anything, it is the pet owner who might be responding to the placebo. The owner who anxiously monitors their pet throughout its time in the trial might in fact be helping the pet get better. It is certainly something that can affect the animal's convalescence that is not down to the drug being tested in the trial.
What this shows is that it is tricky to pin down a real placebo effect in animals, Muñana says.
One way to reduce some of these complicating factors would be to introduce a third group to animal drug trials. This group would receive absolutely no treatment, not even a placebo. This is sometimes known as a "waiting list" group. If the dogs on the placebo do better than the dogs on the waiting list, that might hint of a real placebo effect in animals.
Kienzle started hearing a lot of stories about certain feed supplements and their purportedly wondrous effects in horses
But this is a tricky kind of study to carry out.
Trial participants are hard to come by and the dog owners who do enrol their pet in a study are doing so precisely because they want to take action to make their pet feel better. They might be reluctant to enrol in a study where the chance that their dog is receiving the trial therapy is lower than the chance that it is not.
"You want the owners to feel like they're part of the study and [that their dog] may be getting the active drug," says Muñana.
There are other ways an animal owner's behaviour might have an impact. For instance, it might subtly alter the owner's perception of the animal in a way that changes the animal's behaviour.
Ellen Kienzle is a veterinary researcher who specialises in nutrition and dietetics at the Ludwig Maximilians University of Munich in Germany. She has been interested in the psychology of feeding animals for many years. "It's one thing to have scientific knowledge, and another is getting to the animal. And there is always the owner in between," she says.
We found enormous placebo effects
Kienzle started hearing a lot of stories about certain feed supplements and their purportedly wondrous effects in horses. She wanted to get to the bottom of these anecdotes.
"I got fed up with all these supplements," she says. She could see no solid scientific reason why, say, giving an adult horse a selenium supplement – even if it did not have a selenium deficiency – would help its muscle health.
Despite this, many riders Kienzle heard about were convinced that selenium helped horses with stiff muscles. "It was an ideal model," she says. She designed a study to put two supplements to the test: selenium and vitamin E, alongside a placebo control.
"We found enormous placebo effects," she says. But once again, that was not necessarily because the animals were responding directly to the placebo.
One experienced rider in her study was convinced that the treatment the horse was receiving was making it behave badly
"Especially with horse riding, there is tremendous interaction between the rider and the horse," she says. Kienzle compares riding to dancing. If your dancing partner suddenly spies someone they dislike, you would be able to feel the change in tension in their body. You would know something is up, she says – and that might put you on edge too. "That is how, to my way of thinking, part of the communication between a horse and the rider works."
The horse responds to subtle, even subconscious cues from the rider, like a sensitive dance partner might. "If your mood is good and you think, 'Ah, today he or she is going to perform very well,' the horse will fulfil your expectations. And also, if you expect the horse to make a certain error and that picture is in your mind, your body communicates exactly that to the horse."
The power of this effect can be extraordinarily strong. It is not just about perceptions, but marked changes in behaviour.
Kienzle recalls how one experienced rider in her study was convinced that the treatment the horse was receiving was making it behave badly: it was becoming too strong and almost dangerous. The horse did in fact get stronger and more disobedient throughout the trial. It got to the point that the rider could barely control him.
When she told her in the end that she had had the placebo, the friend broke up with her
The rider actually fell off at one point during the treatment, Kienzle says. Soon afterwards, she withdrew the horse from the scientific trial because of the change in his behaviour. The horse quickly calmed down and began behaving again.
But, as it turns out, the horse had been receiving a placebo rather than one of the supplements – which, Kienzle points out, are most likely placebos themselves. The rider knew that her horse might receive the placebo, Kienzle says, but perhaps subconsciously she had decided that the horse was really receiving the supplement, and that it was having a disruptive effect on his behaviour. "She believed so much that the horse was getting too strong for her that she couldn't hold him any more."
The rider in question was not at all impressed when she found out that her horse had been on a placebo. Kienzle's postgraduate student was a friend of the rider in question, and later shared the results of the experiment. "When she told her in the end that she had had the placebo, the friend broke up with her," Kienzle says.
This highlights another problem with exploring the placebo effect in animals. Experiments can leave people involved in the trials feeling they were duped. There can be a perception of being somehow fooled, which might make people less keen to sign up their pets for the tests.
A major chunk of what we believe constitutes the placebo effect has been in fact discovered in animals
Such is the power of this feeling that it was a good few years before the rider and the postgraduate's friendship got back to normal again, Kienzle says.
So, bearing in mind all the ways that experiment results can be inadvertently altered – and the way that the experiments themselves can create hostilities that discourage people from wanting to participate at all – can we really be sure that animals experience the placebo effect?
"When we're dealing with animals, pets that are owned by people and cared for by people, I think the owner's perceptions can play into things," says Muñana. "But I do think there is also the potential for a physiological basis for the placebo effect in the animal itself."
Edzard Ernst, emeritus professor in complementary medicine at the University of Exeter in the UK, agrees. "A major chunk of what we believe constitutes the placebo effect has been in fact discovered in animals," he says.
This research goes back to the Russian physiologist Ivan Pavlov, who is famous for his work with dogs in the late 19th Century. Pavlov performed experiments in which he trained dogs to expect food when he rang a bell. The dogs became so accustomed, or "conditioned", to hearing the sound of the bell and food arriving, that eventually the sound of the bell alone could make them salivate.
"Today, we believe this [is] a very important part of the placebo effect," says Ernst. "So people who say that animals don't experience placebo effects are ignoring this and they're wrong, I'm afraid."
Placebos work in animals
Veterinary studies investigating the placebo effect are relatively few and far between. But one influential review in 1999 by F.D. McMillan, a US veterinarian, reported some profound placebo responses in laboratory animals.
In one 1982 study, researchers investigated mice that were genetically predisposed to systemic lupus erythematosus, a disease in which the immune system begins attacking healthy tissue. Left untreated, it can cause death. The researchers paired a drug that suppressed this excessive immune activity with sweet water, and made sure that the mice always received the two together. Eventually, when the mice were given only sweet water but no drug, they had the same immune response, just as though they had received the drug as usual.
Putting it simply, "placebos work in animals", Ernst says – even the physiological kind that we might think can only happen in humans. Overall, the effect in animals is very similar to that in humans, he says.
But the element of conscious expectation that can play a role in placebo responses in humans is arguably weaker or not present in animals, he says. "In principle they're the same, but I think there is a different emphasis. Animals don't always have a conscious expectation or they rarely have a conscious expectation of things happening. Humans do have that, for instance, when they go to the doctor or the dentist."
In practice, the fact that studies suggest that placebos can work via conditioning does not mean we should change the way that vets treat animals. Danny Chambers, a practising vet based in Devon in the UK, has campaigned against the use of homeopathic treatments for animals.
The element of conscious expectation that can play a role in placebo responses in humans is arguably weaker or not present in animals
The placebo effect in the mouse experiment suggests that we could condition animals to respond to a placebo as if it were a real therapy. But actually putting that idea into practice would be ethically dubious, Chambers says.
"Even if research somehow proves that there is a Pavlovian response or conditioning response [to a treatment], is it going to be more significant than giving proper painkillers, if the animal needs that?" Chambers says. "If you've got a painful condition, is it fair to rely on the possible Pavlovian response because the animal used to be treated with a real painkiller but now you're giving it a placebo? It's probably unfair to assume that."
Instead, Chambers advocates applying the same rules used in human medicine when treating animals. If there is a conventional treatment available that has been shown to work, that is what should be used.
While there may be a limited future for prescribing placebos in veterinary medicine – as Chambers hopes – placebos will continue to be a staple of researchers who are trying to find new cures and treatments for diseases in animals.
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