Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats

Johari, Illa Syafiqah; Harun, Norsyifa; Sofian, Zarif Mohamed; Shoaib, Mohammed

doi:10.1007/s00213-021-05934-4

Cited by 9 publications

(8 citation statements)

References 51 publications

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“…Moreover, MG pretreatment of animals reduced spontaneous morphine withdrawal (Hassan et al, 2020). In MG physically dependent animals, withdrawal signs were qualitatively different and much weaker than morphine, consistent with its mixed mechanisms of action (Johari et al, 2021). In a mouse physical dependence model (Wilson et al, 2020), naloxone precipitated withdrawal in morphine-but not MG LKTmaintained animals, while LKT pretreatment significantly reduced withdrawal in the morphine-maintained mice.…”

Section: Discussionmentioning

confidence: 67%

“…In the evaluation of physical dependence and withdrawal potential, four studies showed MG did not carry morphinelike physical dependence or withdrawal potential (Harun et al, 2020;Hassan et al, 2020;Wilson et al, 2020;Johari et al, 2021). Moreover, MG pretreatment of animals reduced spontaneous morphine withdrawal (Hassan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Although MG withdrawal signs are weak in rats compared to those from morphine withdrawal, there does appear to be evidence of physical dependence; however, MG withdrawal unlike morphine was not associated with anxiogenic-like subjective symptoms. When using a pentylenetetrazol (PTZ) discrimination trial to evaluate anxiogenic signs in rats after MG or morphine withdrawal precipitated by naloxone, MG showed no substitution to the PTZ discriminative stimulus, while morphine produced a dose-related PTZ-like stimulus, further supporting MG as a novel pharmacotherapeutic intervention for managing opioid use disorder (Johari et al, 2021).…”

Section: Factor/description Citations Main Findings Commentsmentioning

confidence: 99%

“…Factor 1: Actual or relative potential for abuse Intravenous Self-Administration (IV SA) (Prozialeck et al, 2019), (Grundmann et al, 2018;Yue et al, 2018;Coe et al, 2019;Hemby et al, 2019;Garcia-Romeu et al, 2020) No evidence of reward MG pretreatment reduced morphine self-administration Intracranial Self-Stimulation (ICSS) (Negus andMiller, 2014)-(Behnood-Rod et al, 2020) No evidence of reward for MG or 7-OH-MG Drug Discrimination (Hiranita et al, 2020;Reeve et al, 2020;Obeng et al, 2021) MG showed partial generalization to multiple drugs, including morphine Strongest generalization of MG was to unscheduled drugs: phenylephrine and lofexidine 7-OH-MG showed full generalization to morphine Conditioned Place Preference (CPP) (Yusoff et al, 2018;Vijeepallam et al, 2019;Wilson et al, 2020;Japarin et al, 2021) Mixed evidence of CPP Physical Dependence/ Withdrawal (Harun et al, 2020;Hassan et al, 2020;Johari et al, 2021;Hassan et al, 20211778;Harun et al, 2021a) Mixed evidence of weak withdrawal across studies relative to morphine MG reduces morphine withdrawal and differs from morphine withdrawal on some measures Survey Data (Prozialeck et al, 2019), (Grundmann et al, 2018;Coe et al, 2019;Garcia-Romeu et al, 2020), (Singh et al, 2014;Galbis-Reig, 2016;Swogger and Walsh, 2018;Smith et al, 2019; (Prozialeck et al, 2019), (Behnood-Rod et al, 2020), (Hassan et al, 2019;Hiranita et al, 2019;Kruegel et al, 2019;…”

Section: Factor/description Citations Main Findings Commentsmentioning

confidence: 99%

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Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Henningfield¹,

Wang²,

Huestis³

2022

Front. Pharmacol.

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Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; in-vitro receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Factor/description Citations Main Findings Commentsmentioning

confidence: 99%

Section: Factor/description Citations Main Findings Commentsmentioning

confidence: 99%

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Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Henningfield¹,

Wang²,

Huestis³

2022

Front. Pharmacol.

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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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Drug Addiction and Drug Dependency

Maguire

2022

Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays

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Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats

Cited by 9 publications

References 51 publications

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

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

Drug Addiction and Drug Dependency

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