by Whitney Lieberman
figures by Allie Elchert

If you’re a feline enthusiast, you’ve almost certainly noticed the unusual behavior of cats in the presence of catnip. This plant, a member of the mint family, can be purchased at your local pet store or grown in your backyard. A sprinkle of catnip sends most cats into a frenzy characterized by behaviors such as chewing, rolling, and head-rubbing. While this response is certainly amusing, it isn’t just a means of entertainment for our beloved pets. Over the past few years, studies have revealed that in addition to triggering a euphoric response, molecules within catnip and several other plants act as natural insect repellents, protecting cats from getting bitten.

Chemical compounds in catnip and silver vine are responsible for altering cat behavior

The unusual response of domestic cats to catnip (Nepeta cataria) has been well-documented for hundreds of years. Silver vine (Actinidia polygama), a plant native to mountainous regions in eastern Asia, causes cats to exhibit these same behavioral changes. Both catnip and silver vine produce iridoids, a type of chemical known to protect plants against a variety of pests. These molecules prevent the growth of harmful insects and fungi, as well as deter herbivores with their unpalatable taste. In addition to their bug-repellent properties, iridoids boast a number of pharmacological benefits. In fact, plants containing iridoids are prevalent in natural medicine due to their anti-inflammatory and anti-cancer effects.

In the mid-1900s, botanists identified that an iridoid in catnip called nepetalactone is responsible for behavioral changes in cats. Later studies identified that cats perceive the nepetalactone in catnip through their olfactory system, or sense of smell, causing them to chew, lick, and rub the plant leaves. Although the olfactory system was clearly implicated in this “catnip reaction,” researchers remained puzzled by the biological basis by which nepetalactone elicited such a striking behavioral change.

In 2021, a team of researchers from Iwate University in Japan explored the impact of iridoid-producing plants on feline behavior. Past research in this area focused primarily on evaluating catnip, so the Iwate researchers opted to study silver vine instead. Like catnip, silver vine produces iridoids, but previous efforts to pinpoint the exact identity of the iridoids within silver vine were not comprehensive. 

First, the team from Iwate University aimed to identify all chemicals in silver vine that elicit a behavioral change in cats. To do this, they carefully purified material from silver vine leaves into different fractions, each with a unique chemical composition. Cat test subjects were presented with each of these fractions, and their subsequent reactions were observed. All of the test subjects displayed chewing, head-rubbing, and rolling behavior when presented with a plant fraction containing high levels of the iridoid nepetalactol (Figure 1). While nepetalactol is structurally similar to nepetalactone, the iridoid present in catnip, its ability to cause a behavioral change in cats was unknown. To confirm that nepetalactol was able to induce the “catnip reaction” on its own, the researchers synthesized nepetalactol in the lab, presented cat test subjects with this pure material, and observed that it indeed caused the same behavioral response as the plant-derived material.

Figure 1. In this study, chemical compounds from silver vine were purified into six uniquely composed fractions. When provided with one of these fractions, cat test subjects exhibited chewing, head-rubbing, and rolling behavior. An analysis of this fraction revealed that it contained the iridoid nepetalactol.

After proving that nepetalactol can induce a behavioral response in cats, the researchers delved into the biological mechanism driving this behavioral change. Due to the euphoric nature of the “catnip reaction,” the researchers theorized that nepetalactol activates the μ-opioid system in cats. In humans, this system  regulates sensations of pleasure and reward. The μ-opioid system also modulates our pain response, and stimulation of this system with drugs like opioids leads to powerful (and highly addictive) pain-relieving effects.   

To test this theory, researchers took blood samples from cat subjects before and after nepetalactol exposure, then measured levels of the hormone β-endorphin in their blood plasma. β-endorphin triggers the pain-relieving capabilities of the μ-opioid system, and a heightened level of this hormone in the blood is a marker for μ-opioid system activation. As hypothesized, cats exposed to nepetalactol displayed higher levels of β-endorphin in their blood than those that weren’t, implicating the μ-opioid system in the “catnip reaction.”

A natural bug repellent: Nepetalactol protects cats against insect bites

For centuries, humans have taken advantage of the insect-repelling properties of iridoid-containing plants for our own benefit. There are references to the use of catnip as a human bug repellent from texts dating as early as 1638. A recent study from Northwestern University and Lund University in Sweden found that nepetalactone activates an irritant response system present in many insect species, explaining this phenomenon.

With this knowledge in mind, the Iwate University researchers investigated their final question– are the insect-repelling iridoids in these plants also responsible for changing cat behavior? They theorized that after rubbing against or rolling in silver vine, oils from the plant would transfer onto the cats’ fur, providing protection against pests. To test this, the researchers applied either nepetalactol or a non-repellent solution onto test subject cats’ fur and placed the cats into a closed cage containing mosquitos. They observed that a far greater number of insects landed on untreated cats compared to those treated with nepetalactol (Figure 2). In a follow-up study in 2022, the same research group found that the plant-damaging behavior (licking and chewing) that cats exhibit towards iridoid-containing plants are necessary to release nepetalactol, nepetalactone, and other similar chemical compounds. Collectively, these studies suggest that by licking, chewing, and rolling in these plants, cats coat themselves with natural chemicals that confer protection against pests.

Figure 2. The chewing and rolling behavior that cats exhibit towards plants like silver vine and catnip allows them to coat their fur with chemicals that act as natural insect repellents.

Looking forward: Catnip for humans?

Recent investigations into the insect-repellent properties of iridoids have revealed them to be comparable natural alternatives to synthetic insect repellents like N,N-Diethyl-m-toluamide (DEET). Iridoid-producing plants are cheap to grow and their oils are easy to extract, making them a promising candidate for the development of novel insect repellents. This discovery provides a striking example of how natural products, chemicals produced by living organisms, can be harnessed for human use. There are many important examples of this throughout our history– antibiotics like penicillin are produced in fungi, and the cancer drug paclitaxel was first found in tree bark. The utility of these types of natural products was figured out through observation and subsequent investigation of a curious biological phenomenon. Even seemingly inconsequential observations – our pets’ reactions to a common plant, for example – yield fascinating biology that may lead to an impactful discovery. 

Whitney Lieberman is a second-year PhD student in Chemical Biology at Harvard University.

Allie Elchert is a Ph.D. candidate in the Biological and Biomedical Sciences program at Harvard Medical School, where she is studying transcription regulatory processes in yeast.

Cover image by BiancaVanDijk on pixabay.

For more information:

  • This work highlights research from Iwate University. You can read the entire study here.
  • Natural products, molecules produced by living organisms, are powerful tools for drug development efforts. This review discusses the history of these molecules in human health applications.
  • To learn more about the  properties of iridoids, check out this review article.

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