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Kratom’s primary alkaloids “do not have abuse potential,” according to a new study.
The study, published on August 18th, 2020, investigated the “rewarding properties” of kratom’s primary alkaloids, mitragynine and 7-hydroxymitragynine (7-HMG) in rats. The authors used the intracranial self-stimulation (ICSS) model, which involves implanting electrodes in rats’ brains to stimulate and monitor behaviour. In the study model, rats become conditioned to “self-stimulate” by pulling a lever or pushing a button, which induces a pleasurable response.
Researchers can use the ICSS model to assess a drug’s abuse and addiction potential: if a drug is strongly rewarding, it will decrease the rat’s self-stimulation. But if a drug isn’t strongly rewarding, the rat will seek out more self-stimulation. Rats will also seek out more self-stimulation during periods of drug withdrawal.
As you might expect, addictive and easily abused drugs (morphine, heroin, and others) tend to reduce self-stimulation. Since these drugs are rewarding, the rat becomes satisfied and seeks out less self-stimulation. This was the case with morphine, which the researchers administered to rats in the study as a reference drug. As expected, rats receiving morphine participated in less self-stimulation.
But the opposite was true for the kratom alkaloid 7-HMG. According to the authors, 7-HMG “increased the brain reward thresholds,” meaning that rats would seek out more self-stimulation. Based on this observation, the authors concluded that “these kratom alkaloids do not have abuse potential.”
However, the conclusions of another recent kratom study do cast some doubt over whether or not this is true. That study’s authors identified that 7-HMG behaves differently when ingested by humans in comparison to rats and other animals. In human bodies, it converts to mitragynine pseudoindoxyl, which the authors noted “is an even more potent opioid agonist [and] likely to also be highly abusable.”
“The discovery … is … not only unexpected but also may significantly alter our conclusions about the translatability of mitragynine findings using rodent models to the human condition,” they wrote.