November 4, 2021

Mitragynine Reduces Morphine-Related Cognitive Impairment

One of the devastating effects of opiates like morphine is impaired thinking. And unfortunately, the drugs used to wean opiate users off of opiates — such as methadone or buprenorphine — often have a similar effect.

But there's hope: According to a new study, mitragynine, a kratom compound, could help ease opiate addiction without significantly impairing thinking.

Researchers at the Science University of Malaysia conducted the study. They began by inducing morphine withdrawal in male rats and testing their cognitive performance via two tests. As predicted, the morphine withdrawal worsened the rats' performance in both "novel object recognition" (NOR) and "attentional set-shifting" (ASST) tests.

Afterwards, the researchers gave three of the rat groups one of three mitragynine doses. Like many other researchers, they found that the mitragynine remedied the rats' opiate withdrawal signs. And although the mitragynine didn't affect "recognition memory" in one test, it "significantly improved" the rats' thinking in the other. That test, "attentional set-shifting" (ASST), evaluated the rats' ability to ignore or delay rewards — a test of behaviours associated with impulsivity and compulsivity.

During the study, the researchers uncovered another benefit of mitragynine. They noted that repeat morphine use increased levels of a protein called pro-Brain-Derived Neurotrophic Factor (proBDNF) and expression of the enzyme CaMKII in the rats' brains. These increases have several concerning implications: While (mature) BDNF is involved in "neuronal growth and survival," proBDNF can induce "long-term depression and pro-inflammatory responses," according to the authors. Meanwhile, CaMKII is critical to learning and memory, but "overexpression" can impair memory. Thankfully, at all doses, mitragynine also "significantly reduced" levels of proBDNF and CaMKII in the rats' brains.

The researchers concluded that mitragynine could safely and effectively treat opiate-caused addiction and impaired thinking. However, they also acknowledged that mitragynine isn't perfectly safe: Like opiates, it too impaired cognition at chronic and high doses in other rat studies. The caveat is that humans don't generally consume mitragynine at those levels and experience "very little" cognitive impairment, even with chronic use.

You can read the study covered in this article here.

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