mitragynine and Opioid-Related-Disorders

Opioid use disorder (OUD) has become a significant public health issue worldwide. Methadone and buprenorphine are the most common medications used for treating OUD. These drugs have the potential to assist many patients in managing their opioid dependence and withdrawal but they are currently misused and associated with certain compliance issues, side effects, and risk of relapse. As an opioid-like herbal supplement, Mitragyna speciosa Korth or kratom has received increased attention for managing chronic pain and opioid withdrawal symptoms. Nevertheless, the use of kratom as a self-treatment medication for opioid dependence continues to be controversial due to concerns raised about its effectiveness, safety, and abuse liability. The main active alkaloid constituent of the plant, mitragynine, has been shown to act as a partial mu-opioid agonist. Given this pharmacology, studies have been focusing on this psychoactive compound to examine its potential therapeutic values as medication-assisted therapy (MAT). This review aims to provide a current preclinical overview of mitragynine as a prospective novel option for MAT and summarise the recent developments in determining if the plant's active alkaloid could provide an alternative to opioids in the treatment of OUD.

Topics: Analgesics, Opioid; Humans; Mitragyna; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Secologanin Tryptamine Alkaloids; Substance Withdrawal Syndrome

Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States' healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy.. Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments' market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Drug Implants; Humans; Injections, Intramuscular; Methadone; Molecular Targeted Therapy; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Receptors, G-Protein-Coupled; Receptors, Opioid, mu; Secologanin Tryptamine Alkaloids; Thiophenes; Urea; Vaccines

This article reviews the pharmacology, clinical utility, adverse effects, and abuse potential of kratom.. The leaves of. Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. Human pharmacologic, pharmacokinetic, and clinical data are of low quality, precluding any firm conclusions regarding safety and efficacy.

Topics: Analgesics, Opioid; Animals; Drug Overdose; Humans; Opioid-Related Disorders; Receptors, Opioid, delta; Receptors, Opioid, mu; Secologanin Tryptamine Alkaloids

Kratom (Mitragyna speciosa. Korth) is an indigenous medicinal plant of Southeast Asia. This review paper aims to describe the trends of kratom use in Southeast Asia.. A literature review search was conducted through ScienceDirect, Scopus, ProMed and Google Scholar. Twenty-five articles illustrating kratom use in humans in Southeast Asia were reviewed.. Kratom has long been used by rural populations in Southeast Asia as a remedy for common ailments, to fight fatigue from hard manual work, as a drink during social interaction among men, and in village religious functions. Studies based on self-reports suggest that prolonged kratom use does not result in serious health risks or impair social functioning. Two recent trends have also emerged: (a) Kratom is reportedly being used to ease withdrawal from opioid dependence in rural settings; whereas (b) in urban areas, adulterated kratom cocktails are being consumed by younger people to induce euphoria.. Legal sanctions appear to have preceded serious scientific investigations into the claimed benefits of ketum. More objective-controlled trials and experiments on humans need to be conducted to validate self-report claims by kratom users in the community.

Topics: Asia, Southeastern; Humans; Mitragyna; Opioid-Related Disorders; Plants, Medicinal; Secologanin Tryptamine Alkaloids; Substance Withdrawal Syndrome

Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.

Topics: Analgesics, Opioid; Animals; Extinction, Psychological; Mitragyna; Morphine; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Secologanin Tryptamine Alkaloids

Topics: Animals; Heroin; Male; Mice; Mice, Inbred ICR; Morphine Dependence; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Secologanin Tryptamine Alkaloids; Substance Withdrawal Syndrome

Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.

Topics: Animals; Behavior, Animal; Conditioning, Classical; Disease Models, Animal; Dose-Response Relationship, Drug; Extinction, Psychological; Male; Morphine; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Secologanin Tryptamine Alkaloids

Kratom (Mitragyna speciosa) is a native medicinal plant of Southeast Asia widely reported to be used to reduce opioid dependence and mitigate withdrawal symptoms. There is also evidence to suggest that opioid poly-drug users were using kratom to abstain from opioids.. To determine the patterns and reasons for kratom use among current and former opioid poly-drug users in Malaysia.. A total of 204 opioid poly-drug users (142 current users vs. 62 former users) with current kratom use history were enrolled into this cross-sectional study. A validated UPLC-MS/MS method was used to evaluate the alkaloid content of a kratom street sample.. Results from Chi-square analysis showed that there were no significant differences in demographic characteristics between current and former opioid poly-drug users except with respect to marital status. Current users had higher odds of being single (OR: 2.2: 95%CI: 1.21-4.11; p < 0.009). Similarly, there were no significant differences in the duration (OR: 1.1: 0.62-2.03; p < 0.708), daily quantity (OR: 1.5: 0.85-2.82; p < 0.154) or frequency of kratom use between current and former opioid poly-drug users (OR: 1.1: 0.62-2.06; p < 0.680). While both current and former opioid users reported using kratom to ameliorate opioid withdrawal, current users had significantly higher likelihood of using kratom for that purpose (OR: 5.4: 95%CI: 2.81-10.18; p < 0.0001). In contrast, former opioid users were more likely to be using kratom for its euphoric (mood elevating) effects (OR: 1.9: 95%CI: 1.04-3.50; p < 0.035). Results from the UPLC-MS/MS analysis indicated the major alkaloids present in the representative kratom street sample (of approximately 300 mL of brewed kratom) were mitragynine, followed by paynantheine, speciociliatine and speciogynine, as well as low levels of 7-hydroxymitragynine.. Both current and former opioid poly-drug users regularly used kratom (three glasses or about 900 mL daily or the equivalent of 170.19 mg of mitragynine) to overcome opioid poly-drug use problems.

Topics: Adult; Analgesics, Opioid; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Drug Users; Female; Humans; Malaysia; Male; Mitragyna; Opiate Substitution Treatment; Opioid-Related Disorders; Plant Leaves; Plant Preparations; Rural Population; Secologanin Tryptamine Alkaloids; Substance Withdrawal Syndrome; Tandem Mass Spectrometry

Kratom, derived from the plant Mitragyna speciosa, is receiving increased attention as an alternative to traditional opiates and as a replacement therapy for opiate dependence. Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are major psychoactive constituents of kratom. While MG and 7-HMG share behavioral and analgesic properties with morphine, their reinforcing effects have not been examined to date. 7-HMG, but not MG, substituted for morphine self-administration in a dose-dependent manner in the rat self-administration paradigm. Following the substitution procedure, re-assessment of morphine self-administration revealed a significant increase following 7-HMG and a significant decrease following MG substitution. In a separate cohort, 7-HMG, but not MG, engendered and maintained intravenous self-administration in a dose-dependent manner. The effects of pretreatment with nalxonaxine (NLXZ), a μ1 opiate receptor antagonist, and naltrindole (NTI), a δ opiate receptor antagonist, on 7-HMG and morphine self-administration were also examined. Both NLXZ and NTI reduced 7-HMG self-administration, whereas only NLXZ decreased morphine intake. The present results are the first to demonstrate that 7-HMG is readily self-administered, and the reinforcing effects of 7-HMG are mediated in part by μ and δ opiate receptors. In addition, prior exposure to 7-HMG increased subsequent morphine intake whereas prior exposure to MG decreased morphine intake. The present findings indicate that MG does not have abuse potential and reduces morphine intake, desired characteristics of candidate pharmacotherapies for opiate addiction and withdrawal, whereas 7-HMG should be considered a kratom constituent with high abuse potential that may also increase the intake of other opiates.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Mitragyna; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Rats; Receptors, Opioid, delta; Receptors, Opioid, mu; Secologanin Tryptamine Alkaloids; Self Administration

Topics: Amines; Analgesics, Opioid; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Drug Utilization; Gabapentin; gamma-Aminobutyric Acid; Humans; Loperamide; Opioid-Related Disorders; Pharmacovigilance; Practice Patterns, Physicians'; Prescription Drugs; Secologanin Tryptamine Alkaloids; Substance-Related Disorders; United States; United States Food and Drug Administration

Substantial use of the plant kratom for psychoactive effects has driven interest in its abuse liability. Several place conditioning studies suggest abuse liability of the active ingredient mitragynine, though studies of its self-administration have not been published.. Binding of mitragynine to rat brain mu, kappa, and delta opioid receptors was compared to that for heroin and morphine. Self-administration of mitragynine, heroin, methamphetamine, or saline was assessed during single-session substitutions in rats trained to self-administer methamphetamine (0.022 mg/kg/injection, i.v.) during 1-h daily sessions.. Mitragynine had > 2- or ~ 16-fold greater affinity for the mu opioid receptor than, respectively, for kappa or delta opioid receptors. Its affinity for the mu receptor was ~ 200-fold less than that for morphine. In rats trained to self-administer methamphetamine, saline substitutions significantly decreased the number of responses, whereas different doses of methamphetamine (0.002-0.068 mg/kg/injection) or heroin (0.001-0.03 mg/kg/injection) maintained self-administration with maximal responding at 0.022 or 0.01 mg/kg/injection, respectively. In contrast, no dose of mitragynine maintained response rates greater than those obtained with saline. Presession mitragynine treatment (0.1 to 3.0 mg/kg) decreased response rates maintained by heroin but had little effect on responding maintained by methamphetamine across the same range of doses.. These results suggest a limited abuse liability of mitragynine and potential for mitragynine treatment to specifically reduce opioid abuse. With the current prevalence of opioid abuse and misuse, it appears currently that mitragynine is deserving of more extensive exploration for its development or that of an analog as a medical treatment for opioid abuse.

Topics: Animals; Dose-Response Relationship, Drug; Heroin; Male; Morphine; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, mu; Secologanin Tryptamine Alkaloids; Self Administration

Kratom (Mitragyna speciosa) is an herbal preparation with opioid-like effects made from a tree native to Southeast Asia and the Pacific Islands. Increasingly, kratom is used for self-treatment of opioid use disorder and recently has been associated with a multistate outbreak of salmonellosis. Few data are available on the clinical outcomes of kratom use in pregnancy.. We present two cases of pregnant women presenting with kratom dependence. Both women presented with symptoms consistent with opioid withdrawal. Both women were initiated on opioid replacement, with successful treatment of symptoms.. Kratom is an emerging self-treatment for opioid use disorder in the obstetric population. Obstetric care providers should be aware of kratom and consider opioid replacement for pregnant women with kratom dependence.

Topics: Adult; Buprenorphine; Female; Humans; Mitragyna; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Secologanin Tryptamine Alkaloids

Kratom (Mitragyna speciosa) is a plant indigenous to Southeast Asia. Its leaves and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. In a comprehensive review published in 2012, Prozialeck et al presented evidence that kratom had been increasingly used for the self-management of opioid withdrawal and pain in the United States. At the time, kratom was classified as a legal herbal product by the US Drug Enforcement Administration. Recent studies have confirmed that kratom and its chemical constituents do have useful pharmacologic actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule 1 controlled substances, a move that triggered a massive response from kratom advocates. The purpose of this report is to highlight the current scientific and legal controversies regarding kratom.

Topics: Analgesics, Opioid; Drug and Narcotic Control; Humans; Mitragyna; Opioid-Related Disorders; Pain Management; Plant Extracts; Secologanin Tryptamine Alkaloids; Self Care; Substance Withdrawal Syndrome; United States