Scientists: Mitragynine makes mice dumber. Also scientists: Mitragynine makes rats smarter

Last week we told you about a study published in September 2021 that showed cognitive impairment in high-dose mitragynine (MG), the main alkaloid in kratom. The study was also the subject of Kratom Science Journal Club #26. Researchers discovered that very high doses of MG, like THC and morphine, attach to CB1 receptors and cause mice to perform poorly at place-learning and reversal-learning (two training techniques used in animal lab studies), compared to mice given no drugs and mice given the drugs along with a CB1 receptor antagonist.

Another study published in October 2021 seemed to prove the opposite, as rats given MG improved their cognitive functioning.

How can this be? Too often, kratom advocates will look at a study considered positive and highlight it, re-post it, and praise the team of scientists. Prohibitionists will highlight studies shown as negative – usually case reports from someone who ended up in the ER with kratom in their system.

Science performed in good faith is more complex than an argument backed by a political agenda. If kratom use has detriments, which it clearly sometimes does for those who have had negative outcomes, scientists want to understand how this works. If kratom has positives, which for post people it clearly does, scientists want to understand how that works too.

For the sake of argument, let’s entertain the possibility that the team of scientists on the dumb mice study was paid off by the government to make kratom look bad, and the smart rat team is being paid by kratom vendors to make kratom look good. We’ve all heard of sleazy corporations or political groups hiring scientists to misinterpret evidence for financial or political gain (For example, the oil industry hired the same marketing firms to create climate change denial that also denied that cigarettes cause cancer for the tobacco industry).

Well, the only problem with the above hypothesis is the team that found MG causes cognitive impairment in mice, and the team that found MG caused cognitive improvement in rats are both from the University of Science Malaysia. USM is not only a highly reputable institution but the top university for kratom research in the East. Also, two of the researchers participated in both studies. No money from any outside corporation funded either of the studies. They were both publicly funded by grants from the university. So is there government influence? Kratom is illegal in Malaysia, yet many kratom studies that come from this university, including the rat study, could be considered “positive”.

So we can safely, logically assume that these scientists were not motivated to fake an outcome because of funding dollars. Even as inherent bias exists in every scientist, and studies on psychoactive substances are frequently set up to look for negative effects, the peer review process is likely to catch any weakness in evidence, as well as multiple scientists from around the world reading these papers. Quite simply, there is much more to gain by being reputable and honest and conducting quality research.

The conditions that these animals find themselves in were what determined cognitive functioning in these cases. The mice in the first study were given very high doses of MG over a period of time. Doses that aren’t out of the realm of human possibility, but the humans taking these doses would be spending lots of money daily on high-potent extracts. The rats in the second study were in morphine withdrawal. The rats in morphine-withdrawal given mitragynine were found to have higher cognitive performance than rats in morphine withdrawal given a vehicle solution.

Kratom is different for everyone because we’re all different. We are living, transforming, individuals who have different exercise habits, stress levels, health conditions, andwe put different foods and drugs into our bodies. Kratom’s main activity is in the metabolism, where mitragynine metabolizes into other alkaloids like 7-hydroxymitragynine and mitragynine-pseudoindoxyl. As we know, some could have a “high” metabolism, some could have a “low” metabolism. We’re not all the same machine.

Understanding the complexity of science, and getting out of the political binary of right and wrong, good or bad, and cut and dry answers requires overcoming the fear of sometimes being incorrect. Scientists have to test their evidence constantly to do their work, while politicians have to act like they are right 100% of the time. Assigning right and wrong to inert substances is the anti-science, mentally unhealthy foundation of the War on Drugs. The opposite of war is to understand these substances, rather than to declare them an ally or an enemy.


Dumb mice: Iman, I. N., Ahmad, N., Mohd Yusof, N. A., Talib, U. N., Norazit, A., Kumar, J., Mehat, M. Z., Hassan, Z., Müller, C. P., & Muzaimi, M. (2021). Mitragynine (Kratom)-Induced Cognitive Impairments in Mice Resemble Δ9-THC and Morphine Effects: Reversal by Cannabinoid CB1 Receptor Antagonism. Frontiers in pharmacology, 12, 708055.

Smart rats: You, C. Y., Hassan, Z., Müller, C. P., & Suhaimi, F. W. (2021). Mitragynine improves cognitive performance in morphine-withdrawn rats. Psychopharmacology, 10.1007/s00213-021-05996-4. Advance online publication.

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