Humans can often perceive an improvement in their condition if they believe they have received treatment, even if the treatment is a placebo. Do animals also experience perceived improvements following placebo treatments?

The placebo effect, also known as sham treatment, has been a subject of fascination for researchers and doctors. When a person believes they have received treatment for a medical problem, they often experience an improvement, even if they were given a neutral substance that is not expected to have any therapeutic effect. There are examples of the surprising effectiveness of the placebo effect, but the underlying biological mechanisms remain unclear. It is known that sham treatment activates the brain’s reward system and likely also affects the activity of the immune system, thus it is also likely to affect overall body health.

The human body is wonderfully complex, capable of perceiving an improvement in its condition based on the belief that it has received effective treatment. Placebos are effective when patients are aware that they have received treatment, making it seemingly irrational to consider the existence of the placebo effect in animals. For example, a dog brought to the vet may not comprehend the purpose of the visit or understand that the injection it receives is intended to improve its state of health. However, surprisingly, studies have found  instances of the placebo effect occurring in animals. Is this an incorrect conclusion, or can the placebo effect genuinely manifest in animals?

The effectiveness of a placebo relies on the patient's awareness of receiving treatment. Regions of the human brain activated in response to the placebo effect  | Source: Mikkel Juul Jensen / Science Photo Library


What Would Pavlov Say?

In some of the studies, a potential explanation for the experimental results and the observed placebo effect lies in conditioning. We are all familiar with classical conditioning from studies by Pavlov involving dogs and their anticipatory response to food. The animals learn to associate a neutral stimulus with a stimulus that triggers a physical response. For example, dogs learn to associate the sound of a ringing bell with the subsequent presentation of food. For example, dogs learn to connect a ringing bell with food that comes after it. Once this association is established, the dogs' bodies respond to the ringing bell by salivating, even if food does not appear.

Therefore, in the context of animals receiving treatment, their bodies may learn to associate the administration of a drug, for example via injection, with the positive effects of the drug. Subsequently, when these animals receive a sham treatment that is not expected to have a biological effect, they may still respond as if they received the real drug, potentially leading to an improvement in their condition. For example, in one study rats were allowed to receive food after experiencing pain in order to reach it. Some received injections of painkillers while others received injections of a substance with no physical effect. The rats who received the painkiller injection approached the food more frequently because they did not feel pain. Later, all the rats received only the neutral substance, which did not have any effect on their bodies. Surprisingly, the rats that had previously received the painkiller continued to approach the food more often than the rats in the second group, even though they should have experienced regular pain. The researchers concluded that the rats underwent classical conditioning: they learned to associate the injection with the sedative effect that it produced, thus they felt calmer after the injection even when receiving a non-painkilling injection.

Another example involves a study in dogs that experience anxiety when left alone in an unfamiliar environment. Some of the dogs received a sedative when their owners were present, while others were given non-sedative vitamins. The dogs that received the sedative indeed exhibited signs of relaxation following treatment. In a subsequent stage, all the dogs received treatment again before being separated from their owners. In the next stage, all the dogs received treatment again before being separated from their owners. However, this time, they were given vitamins that were not supposed to have a calming effect. Interestingly, the dogs who received the sedative in the previous stage demonstrated fewer symptoms of anxiety than the other dogs. This result suggests that the dogs that received the sedative learned to associate the administration of the drug with the sedative effect it had on their bodies, even when they received a placebo.

A study demonstrated that dogs experiencing anxiety associated the administration of a sham treatment with the relaxation they had experienced during the previous stage with a sedative. A man gives a capsule to a dog | megaflopp, Shutterstock


Indirect Placebo

Another explanation for the placebo effect in animal experiments is that it may not directly impact the animals themselves but rather their owners. In many instances, those who report the success of treatments for animals are the individuals who raise or care for them, and this reporting can be subjective. This could pose a problem, as individuals may perceive effects in line with their optimistic expectations of the treatment their beloved animals receive. For instance, a dog owner might report an improvement in their pet's condition that does not accurately reflect the dog's true medical state.

In a study involving dogs with limping issues caused by joint disease, a treatment was tested for its potential to improve their condition compared to a placebo.The dog owners were aware that their dogs were participating in an experiment, and that only half of them would receive the actual treatment. To assess the improvement in the dogs’ condition, a device measured the amount of force the dogs exerted when walking on a surface with their injured leg. Among dogs who received the placebo, no apparent improvement was observed. In contrast, veterinarians and dog owners reported an improvement, with the owners of dogs who received the placebo treatment reporting a greater improvement than the others, noting an improvement in approximately 57% of cases.

A study investigating dogs with limping due to joint disease revealed that in many cases, their owners reported an improvement even though no actual improvement was detected. A dog walks on a fitness walker | PRESSLAB, Shutterstock


When Time Takes Its Course

Often, the medical condition of the animals does in fact improve in response to a placebo treatment, and it is difficult to find an alternative explanation. A review that assessed the improvement in the condition of dogs with epilepsy found a reduction in the frequency of seizure episodes in 79% of the dogs who received placebo treatment. However, in this case too, the expectations of the dog owners affected the way they reported an improvement in their dogs and thus, due to the significant impact and the objective nature of seizure occurrences, it becomes challenging to attribute the improvement solely to the owners' expectations. But why does the dogs’ condition improve? After all, they are unaware of the nature of the treatment they are receiving…

Not every improvement can be attributed to the placebo effect; there are alternative factors to consider. First, repeated occurrences tend to fluctuate around their average. They naturally gravitate toward the average value. In other words, if one event deviates significantly from the average, it is reasonable to expect the next event to be closer to the average. This phenomenon is known as regression to the mean, and it occurs in various aspects of our lives.

For example, when a dog is afflicted with epilepsy, the number of seizure episodes is expected to fluctuate naturally—sometimes the seizures will be multiple and at other times, fewer. If we begin measuring the frequency of seizures after a period of high frequency, we might observe a false improvement that reflects this natural fluctuation, regardless of the treatment administered to the dog.

Furthermore, an animal's participation in research can influence its physical responses. When an animal takes part in an experiment involving physical treatment, the act of physical contact itself may have an effect on the symptoms and on the severity of the disease. It has been found that patting dogs can lead to a change in their heart rate, and a similar effect has also been observed in horses. Conversely, there is the possibility that animals may experience stress when touched by an unfamiliar person, and this stress may have a negative impact on their medical condition.

Not all improvements can be attributed to the placebo effect, and it is important to explore other potential factors. A handful of active drugs vs. a handful of sham capsules | AllaBond, Shutterstock


Is It All in The Mind?


What are the implications of the placebo effect for the medical treatment of humans? The perplexing findings regarding placebos in animals raise important considerations. Drugs intended for humans initially undergo testing in animals to assess their efficacy compared to a placebo. Understanding the documented placebo effect in animals is essential for making accurate decisions regarding the effectiveness of new drugs. Some of the studies discussed here involved relatively small numbers of participating animals, and the statistical analysis of small sample sizes can be prone to bias. Future studies could benefit from larger sample sizes, the inclusion of control conditions, and the objective measurement of treatment effects, including the monitoring of brain activity. This approach will enable us to gain a deeper understanding of why animals respond to treatments that are not expected to affect them