Mitragynine improves cognitive performance in morphine-withdrawn rats

You, Chiek Yi; Hassan, Zurina; Müller, Christian P.; Suhaimi, Farah Wahida

doi:10.1007/s00213-021-05996-4

Cited by 10 publications

(5 citation statements)

References 68 publications

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“…It might also exert a lipolytic effect [ 40 ••] and antidiabetic action by inhibiting other biological enzymes (α-glucosidase, pancreatic lipase) when combined with the diabetes-2 drug (α-glucosidase inhibitor) acarbose [ 41 ••]. Preclinical evidence has also suggested its potential in treating (i) alcohol use disorder, alcohol withdrawal, and alcohol-seeking behavior, with a large therapeutic window (e.g., [ 42 , 43 ••]); (ii) dependence and withdrawal from opioids (e.g., [ 28 ••, 44 ••]) without anxiogenic symptoms [ 45 ] and by improving simultaneously cognitive performance [ 46 ••]; and (iii) craving and addiction from methamphetamine [ 47 ] (for an overview of preclinical evidence and anecdotal data providing some evidence suggesting kratom’s therapeutic potential, see also Table 1 ).…”

Section: Narrative Review Resultsmentioning

confidence: 99%

Clinical Implications of Kratom (Mitragyna speciosa) Use: a Literature Review

et al. 2023

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Purpose of Review This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications. Recent Findings A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom’s therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings. Summary Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.

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Section: Narrative Review Resultsmentioning

confidence: 99%

Clinical Implications of Kratom (Mitragyna speciosa) Use: a Literature Review

et al. 2023

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“…Morphine hydrochloride was purchased from Labchem (Lipomed). Morphine has been widely used as a comparison for mitragynine for cognitive assessment ( You et al, 2022 ; Yusoff et al, 2016 ) and other behavioural studies ( Harun et al, 2015 ). Mitragynine was isolated from kratom ( M. speciosa ) leaves according to our in-house method ( Chear et al, 2021 ) with a purity of approximately 98%.…”

Section: Methodsmentioning

confidence: 99%

“…Direct contact was defined as the nose coming into contact with or being directed at the object within a minimum distance (≤1 cm). A discrimination ratio greater than 0.5 indicates a preference for and increased interaction with the novel object ( Bevins and Besheer, 2006 ; You et al, 2022 ). The discrimination ratio was calculated as below:…”

Section: Methodsmentioning

confidence: 99%

“…The severity of the cognitive deficits depends on the age of onset of substance abuse with more significant impairment associated with early use ( Jordan and Andersen, 2017 ). Since kratom has been claimed to have both therapeutic and addictive potentials ( Gutridge et al, 2020 ; Hassan et al, 2020 ; Vicknasingam et al, 2020 ; You et al, 2022 ), the widespread use of kratom in adolescents further highlighted the need for a better understanding of the effects of adolescent kratom exposure on multiple aspects including cognitive behaviours.…”

Section: Introductionmentioning

confidence: 99%

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Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats

et al. 2022

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Adolescence is a critical developmental period during which exposure to psychoactive substances like kratom (Mitragyna speciosa) can cause long-lasting deleterious effects. Here, we evaluated the effects of mitragynine, the main alkaloid of kratom, and lyophilised kratom decoction (LKD) on cognitive behaviours and brain metabolite profiles in adolescent rats. Male Sprague-Dawley rats (Postnatal day, PND31) were given vehicle, morphine (5 mg/kg), mitragynine (3, 10, or 30 mg/kg), or LKD (equivalent dose of 30 mg/kg mitragynine) for 15 consecutive days. Later, a battery of behavioural testing was conducted, brain was extracted and metabolomic analysis was performed using LCMS-QTOF. The results showed that mitragynine did not affect the recognition memory in the novel object recognition task. In the social interaction task, morphine, mitragynine, and LKD caused a marked deficit in social behaviour, while in Morris water maze task, mitragynine and LKD only affected reference memory. Metabolomic analysis revealed distinct metabolite profiles of animals with different treatments. Several pathways that may be involved in the effects of kratom exposure include arachidonic acid, pantothenate and CoA, and tryptophan pathways, with several potential biomarkers identified. These findings suggest that adolescent kratom exposure can cause cognitive behavioural deficits that may be associated with changes in the brain metabolite profiles.

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“…One recent study, which studied a number of cognitive domains in heroin users, found that cognitive impairment was specifically related to the route of administration) used (Ghosh et al 2023); intravenous injection was associated with memory deficits while inhalation was associated with decreased ability to maintain attentional set. Injecting rodents with opioid drugs can likewise impair performance on tests of impulsivity (Pattij et al 2009), cognitive flexibility (You et al 2022), and working memory (Braida et al 1994). Repeated opioid administration also degraded performance on tests of spatial navigation; however, the majority of such studies focus on behavioral outcomes of testing during ongoing treatment with repeated injections (Lu et al 2010; Pu et al 2002) or shortly after the discontinuation of a repeated opioid injection regimen during withdrawal (Luo et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Persistent effects of repeated adolescent and adult heroin vapor inhalation in female Wistar rats

Gutierrez,

Taffe

2024

Preprint

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Adolescent drug exposure has been associated with more severe mental health outcomes related to substance abuse and anxiety disorders. The aim of the present study was to contrast the long-term effects of repeated heroin vapor inhalation during adolescence with similar heroin exposure in adulthood. Groups of female Wistar rats underwent twice daily 30-minute sessions of heroin or propylene glycol (control) vapor inhalation from postnatal days (PND) 36-45 or PND 85-94, respectively. Nociception was assessed after vapor inhalation sessions and forty days later, for the Adolescent-Exposed and Adult-Exposed groups. Anxiety-like behavior was assessed with an elevated plus-maze (EPM) and spatial learning was assessed with a Barnes maze. Acute effects of naloxone (0.3 mg/kg, i.p.) and heroin (0.5 and 1.0 mg/kg, s.c.) on thermal nociception were determined on PND 140/189 and PND 149/198, respectively. Repeated heroin vapor inhalation produced anti-nociceptive tolerance across sessions in both adolescent and adult rats, with the adolescents exhibiting more complete tolerance. Heroin vapor inhalation produced anxiolytic effects, regardless of age of exposure. There were no effects of heroin on spatial learning. Naloxone produced acute hyperalgesia in all but the Adolescent-Exposed heroin group, and heroin anti-nociception was blunted in both heroin-exposed groups at the highest heroin dose. Repeated heroin vapor inhalation can produce lasting effects on nociception and anxiety-like behavior that persist for months after the exposure. Importantly, these findings suggest that adolescent exposure to heroin vapor produces specific effects on nociception that are not observed when exposure occurs in adulthood.

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Mitragynine improves cognitive performance in morphine-withdrawn rats

Cited by 10 publications

References 68 publications

Clinical Implications of Kratom (Mitragyna speciosa) Use: a Literature Review

Clinical Implications of Kratom (Mitragyna speciosa) Use: a Literature Review

Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats

Persistent effects of repeated adolescent and adult heroin vapor inhalation in female Wistar rats

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