Mini review: Potential therapeutic values of mitragynine as an opioid substitution therapy

Harun, Norsyifa; Kamaruzaman, Nur Azzalia; Sofian, Zarif Mohamed; Hassan, Zurina

doi:10.1016/j.neulet.2022.136500

Cited by 9 publications

(10 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of evidence for respiratory depressant effects in rats documented here does not rule out the possibility of respiratory depressant effects in some human conditions and in combination with other substances. Mitragynine in isolation and kratom produce diverse opioid and nonopioid mediated effects that warrant further study (Ahmad et al 2022;Harun et al 2022;Behnood-Rod et al 2020;Hemby et al 2019;Henningfield et al 2018Henningfield et al , 2022Reeve et al 2020;Sharma and McCurdy 2021;Wilson et al 2020;Yue et al 2018). However, as compared to opioids and other substances that contributed to the 2021 annualized rate of 108,000 drug overdose deaths, the relative risk of kratom appears to be far lower than that of opioids, methamphetamine and cocaine, alcohol, and many other substances of abuse (CDC 2021;Giroir 2018;Henningfield et al 2019; United Nations Commission on Narcotic Drugs 2021).…”

Section: Discussionmentioning

confidence: 99%

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Henningfield

Rodricks

Magnuson³

et al. 2022

Psychopharmacology

View full text Add to dashboard Cite

Rationale Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway. Objectives Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188–197, 2020). Methods Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride. Findings Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related. Conclusions Consistent with mitragynine’s pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Henningfield

Rodricks

Magnuson³

et al. 2022

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…Some of the synthetic medications such as methadone and buprenorphine used in the treatment of opioid addiction are misused and linked to side effects and relapse risk. Therefore, the urge to find a safer therapeutic option is highly demanded [48] …”

Section: Resultsmentioning

confidence: 99%

“…Kratom products have also been found to be contaminated with opioids, ethanol, stimulants, benzodiazepines, and cough syrup containing codeine or diphenhydramine and quetiapine, as an illegal method of achieving stronger euphoric effects [81,82] . The adulterated kratom products represent a serious hazard because of the possible herb‐drug interactions [48] . About 40 different alkaloids have been isolated from Mitragyna speciosa till now.…”

Section: Resultsmentioning

confidence: 99%

“…The pharmacological effect of kratom is attributed to Mitragynine ( Figure 4). Other alkaloids such as paynantheine, corynantheidine, 7‐hydroxamitragynine, speciogynine, and speciociliatine ( Figure 4), also participate in the pharmacological effects of kratom [48,78] …”

Section: Resultsmentioning

confidence: 99%

“…The alkaloid contents could differ significantly because of the plant's geographic origin, age, and season [83,84] . These variations in the alkaloid contents result in the challenge of assessing kratom use in drug addiction treatment [48] . Mitragynine and 7‐hydroxy mitragynine being the main phytoconstituents of kratom are atypical opioids.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Natural Products for the Treatment of Drug Addiction: Narrative Review

Raslan

2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Drug addiction is considered a chronic disorder affecting the individual's life, his/her family and society. Up till now the treatment of drug addiction is considered a problematic issue. Synthetic drugs available for the treatment of drug addiction are few, of limited efficacy and associated with serious side effects. Therefore, there is a continuous search for better therapeutic agents for drug addiction. Natural products represent a promising source for drug addiction treatment. This review summaries drug addiction definition, its mechanism of action, its types, its diagnosis, factors affecting its development and different available approaches for its treatment especially the use of natural products. Six plants were discussed thoroughly in this review, including, Tabernanthe

show abstract

Mitragynine inhibits hippocampus neuroplasticity and its molecular mechanism

Yunusa,

Hassan,

Müller

2023

Pharmacol. Rep

View full text Add to dashboard Cite

Background Mitragynine (MIT), the primary indole alkaloid of kratom (Mitragyna speciosa), has been associated with addictive and cognitive decline potentials. In acute studies, MIT decreases spatial memory and inhibits hippocampal synaptic transmission in long-term potentiation (LTP). This study investigated the impacts of 14-day MIT treatment on hippocampus synaptic transmission and its possible underlying mechanisms. Methods Under urethane anesthesia, field excitatory post-synaptic potentials (fEPSP) of the hippocampal CA1 region were recorded in the Sprague Dawley (SD) rats that received MIT (1, 5, and 10 mg/kg), morphine (MOR) 5 mg/kg, or vehicle (ip). The effects of the treatments on basal synaptic transmission, paired-pulse facilitation (PPF), and LTP were assessed in the CA1 region. Analysis of the brain's protein expression linked to neuroplasticity was then performed using a western blot. Results The baseline synaptic transmission's amplitude was drastically decreased by MIT at 5 and 10 mg/kg doses, although the PPF ratio before TBS remained unchanged, the PPF ratio after TBS was significantly reduced by MIT (10 mg/kg). Strong and persistent inhibition of LTP was generated in the CA1 region by MIT (5 and 10 mg/kg) doses; this effect was not seen in MIT (1 mg/kg) treated rats. In contrast to MIT (1 mg/kg), MIT (5 and 10 mg/kg) significantly raised the extracellular glutamate levels. After exposure to MIT, GluR-1 receptor expression remained unaltered. However, NMDAε2 receptor expression was markedly downregulated. The expression of pCaMKII, pERK, pCREB, BDNF, synaptophysin, PSD-95, Delta fosB, and CDK-5 was significantly downregulated in response to MIT (5 and 10 mg/kg) exposure, while MOR (5 mg/kg) significantly raised synaptophysin and Delta fosB expression. Conclusion Findings from this work reveal that a smaller dose of MIT (1 mg/kg) poses no risk to hippocampal synaptic transmission. Alteration in neuroplasticity-associated proteins may be a molecular mechanism for MIT (5 and 10 mg/kg)-induced LTP disruption and cognitive impairments. Data from this work posit that MIT acted differently from MOR on neuroplasticity and its underlying mechanisms. Graphical abstract

show abstract

Mini review: Potential therapeutic values of mitragynine as an opioid substitution therapy

Cited by 9 publications

References 91 publications

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Natural Products for the Treatment of Drug Addiction: Narrative Review

Mitragynine inhibits hippocampus neuroplasticity and its molecular mechanism

Contact Info

Product

Resources

About