Abstract
Mitragyna speciosa (“kratom”), employed as a traditional medicine to improve mood and relieve pain, has shown increased use in Europe and North America. Here, the dose-dependent effects of a purified alkaloid kratom extract on neuronal oscillatory systems function, analgesia, and antidepressant-like behaviour were evaluated and kratom-induced changes in ΔFosB expression determined. Male rats were administered a low or high dose of kratom (containing 0.5 or 1 mg/kg of mitragynine, respectively) for seven days. Acute or repeated low dose kratom suppressed ventral tegmental area (VTA) theta oscillatory power whereas acute or repeated high dose kratom increased delta power, and reduced theta power, in the nucleus accumbens (NAc), prefrontal cortex (PFC), cingulate cortex (Cg) and VTA. The repeated administration of low dose kratom additionally elevated delta power in PFC, decreased theta power in NAc and PFC, and suppressed beta and low gamma power in Cg. Suppressed high gamma power in NAc and PFC was seen selectively following repeated high dose kratom. Both doses of kratom elevated NAc-PFC, VTA-NAc, and VTA-Cg coherence. Low dose kratom had antidepressant-like properties whereas both doses produced analgesia. No kratom-induced changes in ΔFosB expression were evident. These results support a role for kratom as having both antidepressant and analgesic properties that are accompanied by specific changes in neuronal circuit function. However, the absence of drug-induced changes in ΔFosB expression suggest that the drug may circumvent this cellular signaling pathway, a pathway known for its significant role in addiction.
Highlights
Mitragyna speciosa, commonly referred to as kratom, is a tree species that is native to Southeast Asia and it has been used by individuals for centuries both recreationally and medicinally to improve mood and manage acute and chronic pain (Singh et al, 2016; Ismail et al, 2019)
Similar to that observed in nucleus accumbens (NAc), these findings demonstrate prominent effects of kratom in the low frequency range in the prefrontal cortex (PFC), with additional effects to suppress high gamma power
Following a single injection of kratom, we found that low dose kratom significantly reduced immobility in the forced swim test (FST) compared with saline controls (88.8 ± 25.5 versus 176.8 ± 40.1, p < 0.001) (F(2,30) 16.3, p < 0.001)
Summary
Commonly referred to as kratom, is a tree species that is native to Southeast Asia and it has been used by individuals for centuries both recreationally and medicinally to improve mood and manage acute and chronic pain (Singh et al, 2016; Ismail et al, 2019). The increase of kratom sales across Europe and North America have resulted in growing concerns over its safety, with several European countries and states within the United States banning the plant or instituting age restrictions in its use (Cinosi et al, 2015) Despite these restrictions, it is estimated there are several million users of kratom (Henningfield et al, 2018). Consumption of kratom leaves has been reported to have dose-dependent effects, in that lower doses have been found to induce mild stimulantlike effects and higher doses have been found to induce opioid like analgesic effects (Kruegel and Grundmann, 2018) These outcomes of ingesting the plant material have historically been attributed to only two alkaloids that are typically present within the kratom leaf material, namely mitragynine and its derivative 7hydroxymitragynine (7-HMG), it is well established that there are at least 40 other alkaloids that accumulate within the plant, albeit in various amounts (Prozialeck et al, 2012; Eastlack et al, 2020). Almost nothing is known about the biological properties of these other alkaloids, or of the combined biological effects of the plant as a whole
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