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2.
ACS Chem Neurosci ; 12(14): 2661-2678, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34213886

RESUMO

Dry leaves of kratom (mitragyna speciosa) are anecdotally consumed as pain relievers and antidotes against opioid withdrawal and alcohol use disorders. There are at least 54 alkaloids in kratom; however, investigations to date have focused around mitragynine, 7-hydroxy mitragynine (7OH), and mitragynine pseudoindoxyl (MP). Herein, we probe a few minor indole and oxindole based alkaloids, reporting the receptor affinity, G-protein activity, and ßarrestin-2 signaling of corynantheidine, corynoxine, corynoxine B, mitraciliatine, and isopaynantheine at mouse and human opioid receptors. We identify corynantheidine as a mu opioid receptor (MOR) partial agonist, whereas its oxindole derivative corynoxine was an MOR full agonist. Similarly, another alkaloid mitraciliatine was found to be an MOR partial agonist, while isopaynantheine was a KOR agonist which showed reduced ßarrestin-2 recruitment. Corynantheidine, corynoxine, and mitraciliatine showed MOR dependent antinociception in mice, but mitraciliatine and corynoxine displayed attenuated respiratory depression and hyperlocomotion compared to the prototypic MOR agonist morphine in vivo when administered supraspinally. Isopaynantheine on the other hand was identified as the first kratom derived KOR agonist in vivo. While these minor alkaloids are unlikely to play the majority role in the biological actions of kratom, they represent excellent starting points for further diversification as well as distinct efficacy and signaling profiles with which to probe opioid actions in vivo.


Assuntos
Alcoolismo , Mitragyna , Analgésicos Opioides/farmacologia , Animais , Indóis/farmacologia , Camundongos , Oxindóis/farmacologia , Receptores Opioides , Alcaloides de Triptamina e Secologanina
3.
Drug Alcohol Depend ; 226: 108879, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34216869

RESUMO

BACKGROUND: Mitragyna speciosa, referred to as "kratom", is increasingly used in the United States for self-treating pain, psychiatric, and substance use disorder symptoms. It is used by some to attenuate opioid withdrawal and as a longer-term drug substitute. Most self-report data have come from online surveys, small in-person surveys, and case reports. These may not be representative of the broader kratom-using population. PURPOSE: Analyze user-generated social media posts to determine if independent, descriptive accounts are generally consistent with prior U.S. kratom survey findings and gain a more nuanced understanding of kratom use patterns. METHODS: Reddit posts mentioning kratom from 42 subreddits between June 2019-July 2020 were coded by two independent raters. FINDINGS: Relevant posts (number of comments, upvotes, and downvotes) from 1274 posts comprised the final sample (n = 280). Of the 1521 codes applied, 1273 (83.69%) were concordant. Desirable kratom effects were described among a majority, but so too were adverse effects. Reports of kratom as acute self-treatment for opioid withdrawal were more prominent compared to longer-term opioid substitution. Quantitative analysis found higher kratom doses associated (p < .001) with greater odds of reported kratom addiction (OR = 3.56) or withdrawal (OR = 5.88), with slightly lower odds of desirable effects (OR = 0.53, p = .014). Despite perceived therapeutic benefits, kratom was characterized by some in terms of addiction that, in some cases, appeared dose-dependent. Polydrug use was also prominently discussed. CONCLUSIONS: Results validated many prior survey findings while illustrating complexities of kratom use that are not being fully captured and require continued investigation.


Assuntos
Mitragyna , Mídias Sociais , Síndrome de Abstinência a Substâncias , Analgésicos Opioides/uso terapêutico , Humanos , Dor/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Estados Unidos/epidemiologia
4.
Emerg Med Clin North Am ; 39(3): 677-687, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215409

RESUMO

In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.


Assuntos
Drogas Desenhadas/efeitos adversos , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Canabinoides/efeitos adversos , Drogas Desenhadas/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Loperamida/administração & dosagem , Loperamida/efeitos adversos , Mitragyna/efeitos adversos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Fenetilaminas/efeitos adversos
5.
Molecules ; 26(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204457

RESUMO

Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53-2.91 g) and showed a constant mitragynine content (6.53-7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies.


Assuntos
Mitragyna/química , Extratos Vegetais/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Animais , Células HEK293 , Células HeLa , Humanos , Masculino , Camundongos , Mitragyna/metabolismo , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Alcaloides de Triptamina e Secologanina/química , Solventes/química
6.
Am J Forensic Med Pathol ; 42(4): 341-349, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091497

RESUMO

ABSTRACT: Mitragyna speciosa, commonly known as the kratom tree, has been utilized in Southeast Asia for centuries for its opioid-like effects. Kratom has been available in the United States for the past decade and has grown increasingly popular despite a lack of clinical research to determine its safety. With its widespread use, there have been an increasing number of fatalities. This study aims to establish a potential lethal range for mitragynine, the active compound in kratom, by investigating the toxicology reports of 35 deaths in Northern Nevada between 2015 and 2020. Mitragynine concentrations ranged from 8.7 to 1800 ng/mL (n = 27) in cases with drug toxicity as the cause of death; in 1 case, the sole intoxicant was mitragynine with a blood concentration of 950 ng/mL. In cases with nonmitragynine causes of death, the concentration was 110 to 980 ng/mL (n = 8). There was no statistically significant difference in blood concentrations between cases where mitragynine was not listed as a cause of death (mean, 315 ± 297.2 ng/mL) and cases in which mitragynine contributed to death (mean, 269.4 ± 382.5 ng/mL; P < 0.201). A literature review is also presented.


Assuntos
Mitragyna , Alcaloides de Triptamina e Secologanina , Analgésicos Opioides , Nevada , Estados Unidos
7.
Physiol Behav ; 239: 113499, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34146575

RESUMO

Mitragynine (MG), the most prevalent bioactive alkaloid in kratom, displays nanomolar affinity for µ, κ and δ opioid receptors and produces opioid-dependent antinociception and dependence in rats. Here, using a battery of behavioral assays, we investigated MG effects in planarians. Acute MG exposure (< 100 µM) did not affect planarian motility or environmental preference, but reduced motility was detected during abstinence from chronic MG (1, 10 µM). MG (10 µM) produced place conditioning effects that were reduced by naltrexone (10  µΜ). These results suggest that MG produces opioid-sensitive reinforcing effects in planarians and MG pharmacology is conserved across different species.


Assuntos
Mitragyna , Planárias , Alcaloides de Triptamina e Secologanina , Animais , Naltrexona/farmacologia , Ratos , Alcaloides de Triptamina e Secologanina/farmacologia
8.
J Am Geriatr Soc ; 69(8): 2176-2184, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34143890

RESUMO

BACKGROUND: In recent years, use of the herbal supplement kratom has increased in the United States. The reasons for use include pain relief, particularly as a substitute for opioids. OBJECTIVES: To describe epidemiologic trends in kratom-related exposures among older adults reported to U.S. poison centers. DESIGN: Retrospective analysis of American Association of Poison Control Center's National Poison Data System (NPDS). SETTING: Data from all U.S. poison centers from 2014 to 2019 were examined. PARTICIPANTS: Kratom exposure cases involving adults aged 18 and older. Kratom cases were identified by product and NPDS generic codes. Non-human and information-only calls were excluded. Data were examined for all calls for exposures among adults, with a focus on older adults aged 60-69 years and above 70 years. MEASUREMENTS: Descriptive analyses were used to characterize individual demographic, exposure information, clinical effects, and medical outcomes associated with kratom exposures among older adults. Comparisons across age groups (18-59, 60-69, and 70+ years) were made using Fisher's exact tests. RESULTS: Among 3484 kratom-related exposures reported between 2014 and 2019, 4.6% (n = 162) were among adults over 60 years. The number of kratom-related exposures increased over time. Most cases originated with calls from healthcare facilities (81.1%) and involved kratom as a single ingestant (63.0%). The reason for most ingestions was intentional (74.5%). One in five exposures among adults aged 70 and older involved an adverse reaction (e.g., drug interaction; 21.9%), compared with 12.3% among ages 60-69 and 9.6% among ages 18-59 years. Neurological and cardiovascular clinical effects were observed. Twenty-three deaths were observed among older adults. CONCLUSION: Healthcare providers and older adult patients should be aware of the potential risks of kratom use, including medication interactions and falls. When reviewing medication lists, providers should query this population for all medications and substances being used, especially in people being treated for pain.


Assuntos
Mitragyna/envenenamento , Centros de Controle de Intoxicações/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitragyna/efeitos adversos , Envenenamento/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Nat Commun ; 12(1): 3858, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158473

RESUMO

Mitragynine (MG) is the most abundant alkaloid component of the psychoactive plant material "kratom", which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method for selective functionalization of the unexplored C11 position of the MG scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. Through this work we discover that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. 7-Hydroxymitragynine (7OH), the parent compound with low efficacy on par with buprenorphine, is transformed to an even lower efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.


Assuntos
Mitragyna/química , Extratos Vegetais/farmacologia , Receptores Opioides mu/agonistas , Alcaloides de Triptamina e Secologanina/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Etilenoglicol/química , Humanos , Camundongos Knockout , Modelos Químicos , Estrutura Molecular , Extratos Vegetais/química , Ligação Proteica , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Alcaloides de Triptamina e Secologanina/química
10.
Int J Drug Policy ; 95: 103197, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33991888

RESUMO

Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Southeast Asia, which has been used in traditional medicine for centuries. Despite local communities in Southern Thailand viewing Kratom as a traditional remedy and not as an illicit drug, Thailand criminalized Kratom in 1943 which has led to tensions between government authorities and local communities. This study employed a mixed-method design to explore alternative ways to decriminalize Kratom, using a Participatory Action Research framework to develop a community charter to better manage Kratom in Tambon Namphu, a rural sub-district in Southern Thailand. Quantitative data consisted of face-to-face surveys with 457 Tambon Namphu residents, 104 students and teachers and on-line self-complete surveys conducted with 1,058 people outside Tambon Namphu. Qualitative data were collected using focus groups, in-depth interviews and through public forums conducted with Tambon Namphu residents. Survey results indicate that most participants agreed with decriminalization of both Kratom cultivation and consumption and typically reported positive attitudes towards people who use Kratom. The most common reasons for supporting Kratom decriminalization were Kratom's perceived benefits for work productivity and health. People had more positive attitudes towards the consumption of fresh Kratom leaves than Kratom decoctions which were deemed more harmful. Participatory action research methods were used to pilot the development of a community consensus framework for Kratom control in Donsai, a village of 127 households. Following successful piloting, the community consensus framework on Kratom control was adopted in Donsai, adapted across Tambon Namphu and then extended to cover 135 villages across Thailand.


Assuntos
Drogas Ilícitas , Mitragyna , Atitude , Humanos , Folhas de Planta , Tailândia
11.
WMJ ; 120(1): 54-61, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33974767

RESUMO

OBJECTIVES: An increasing number of Americans are turning to kratom for self-management of various pain, anxiety, and mood states and as an opioid substitute. Addiction to this unique botanical develops and carries a high relapse risk and, to date, there are no guidelines on how to maintain long-term abstinence. The aim of this article is to compile all available information on management of "kratom use disorder" (KUD)-as coined here-from the literature, with evidence from the clinical practice of expert addictionologists in an attempt to develop a standard of care consensus. METHODS: A systematic literature search was conducted to capture all relevant cases pertaining to maintenance treatment for KUD. Results were supplemented with case reports and scientific posters gleaned from reliable online sources and conference proceedings. Additionally, a survey of members of the American Society of Addiction Medicine (ASAM) was administered to assess the practice patterns of experts who treat patients with KUD in isolation of a comorbid opioid use disorder (OUD). RESULTS: Based on a literature review, 14 reports exist of long-term management of KUD, half of which do not involve a comorbid OUD. Pharmacological modalities utilized include mostly buprenorphine but also a few cases of naltrexone and methadone, all with favorable outcomes. This is supported by the results of the expert survey, which demonstrated that those who have managed KUD in isolation of a comorbid OUD reported having utilized buprenorphine (89.5%), as well as the other medications for opioid use disorder (MOUD). CONCLUSIONS: This is the first comprehensive review to examine the existing literature referring to management of KUD in combination with a survey of current experts' clinical consensus regarding pharmacological management. Based on this information, it seems reasonable that the indication for MOUD should be extended to cases of moderate to severe KUD.


Assuntos
Buprenorfina , Mitragyna , Transtornos Relacionados ao Uso de Opioides , Humanos , Metadona , Naltrexona , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estados Unidos
12.
J Psychoactive Drugs ; 53(2): 127-139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34003732

RESUMO

Mitragynine is a major psychoactive alkaloid in leaves of kratom (Mitragyna speciosa Korth.). To understand its disposition in organs, this study aimed to develop a physiologically based pharmacokinetic (PBPK) model that predicts mitragynine concentrations in plasma and organ of interests in rats and humans. The PBPK model consisted of six organ compartments (i.e. lung, brain, liver, fat, slowly perfused tissues, and rapidly perfused tissue). From systematic searching, three pharmacokinetic studies of mitragynine (two studies in rats and 1 study in humans) were retrieved from the literature. Berkeley Madonna Software (version 8.3.18) was used for model development and model simulation. The developed PBPK model consisted of biologically relevant features following involvement of (i) breast cancer-resistant protein (BCRP) in brain, (ii) a hepatic cytochrome P450 3A4 (CYP3A4)-mediated metabolism in the liver, and (iii) a diffusion-limited transport in fat. The simulations adequately describe simulated and observed data in the two species with different dosing regimens. PBPK models of mitragynine in rats and humans were successfully developed. The models may be used to guide optimal mitragynine dosing regimens.


Assuntos
Mitragyna , Alcaloides de Triptamina e Secologanina , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Animais , Humanos , Proteínas de Neoplasias , Extratos Vegetais , Ratos
13.
Am J Forensic Med Pathol ; 42(4): 335-340, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34054017

RESUMO

ABSTRACT: Kratom is a psychoactive substance in Thailand. The major psychoactive chemical component of Kratom is mitragynine. This study aims to elucidate the characteristics and pathologies of autopsied cases where mitragynine was present and quantify the amounts of mitragynine. The autopsy reports in which the blood samples were positive for mitragynine were selected in Ramathibodi Hospital between January 2015 and December 2019. Data from autopsy reports comprised sex, age, circumstances of death, pathological findings, other substances, causes of death, and mitragynine concentrations. Mitragynine was quantitatively analyzed using liquid chromatography-mass spectrometry/mass spectrometry. Twenty-four cases from 2160 autopsy cases were found to be positive for mitragynine. The most commonly observed pathological findings were pulmonary edema (7 cases) and coronary atherosclerosis (6 cases). Antihistamine (8 cases), ethanol (4 cases), and amphetamine (4 cases) were commonly found. The mitragynine concentrations were 0.0035 to 3.6 mg/L (median 0.069). One interesting case involved a 43-year-old man whose pathological findings showed chronic asthma with a high concentration of mitragynine in the blood (3.6 mg/L), although no other substances were detected. In conclusion, the use of mitragynine may be a direct or indirect cause of death, whereas the lethal concentration has yet to be clearly determined.


Assuntos
Mitragyna , Adulto , Causas de Morte , Cromatografia Líquida , Humanos , Estudos Retrospectivos , Espectrometria de Massas em Tandem
14.
Epilepsy Behav ; 121(Pt A): 108057, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34052638

RESUMO

We report a case series of young adults who were admitted to hospital with seizures after regular kratom beverage consumption. This study aimed to determine kratom consumption habits and seizure characteristics and to explore whether chronic kratom ingestion without concomitant drug abuse leads to recurrent seizure or epilepsy. All patients underwent blood investigations, a brain computed tomography (CT) scan, electroencephalography, and urine testing for mitragynine and drug toxicology. Eleven participants who had a positive urine mitragynine test were included in the study. The longest duration of kratom consumption was 84 months: - most drank more than eight times per month (>200 mL/drink). Seizure developed within 10 minutes or up to 72 hours post-ingestion. Seizure occurred one to three times per year in most cases. Four patients had a focal to bilateral tonic-clonic seizure whereas the remaining participants had a generalized tonic-clonic seizure. Four patients mixed kratom with diphenhydramine syrup, and one patient took methamphetamine. Two patients had positive urine results for recreational drugs (opioid and amphetamine). This study provided indirect evidence that chronic kratom use with or without concomitant drug abuse can cause recurrent seizures in susceptible individuals, which may progress to epilepsy or require antiepileptic medication.


Assuntos
Drogas Ilícitas , Mitragyna , Bebidas , Humanos , Malásia , Convulsões , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-34000147

RESUMO

OBJECTIVE: To understand and highlight the current issues, emerging trends, and regulations of kratom in the United States. DATA SOURCES: PubMed and PubMed Central of the National Library of Medicine, MEDLINE, PsycINFO, and ClinicalTrials.gov databases were utilized. STUDY SELECTION: Studies published between January 1, 2000, and June 30, 2020, were accessed by using the MeSH term mitragyna in the context of toxicity, safety, and legislation and jurisprudence. DATA EXTRACTION: The final qualitative synthesis included 11 studies by following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement guidelines. RESULTS: The US Drug Enforcement Administration (DEA) initially proposed to place kratom under Schedule I of the Controlled Substances Act, but the DEA later withdrew the intent, and kratom is still a legal substance in most of the United States. A low to moderate kratom dose produces mild stimulant properties, whereas large doses produce sedative effects that are identical to opiates. Its regular use at a higher dose is associated with dependence. Management of overdose is similar to that of patients presenting with opioid abuse, although kratom may potentially pose a higher risk for drug toxicity and organ injury compared to opioids due to intrinsic properties and adulteration. There is no clinical evidence for its safety and efficacy. The US Food and DEA do not recognize any legitimate medical use of kratom. CONCLUSIONS: Kratom is an emerging public health concern and is abused as an alternative to opioids. Stringent policies and public awareness campaigns are required to curb the perception of its safe use, which needs to be substantiated with well-designed clinical trials.


Assuntos
Estimulantes do Sistema Nervoso Central , Overdose de Drogas , Mitragyna , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estados Unidos
16.
Am J Prev Med ; 61(2): 240-245, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34027890

RESUMO

INTRODUCTION: Kratom is a plant with partial opioid agonist effects, and its use has become popular to ameliorate symptoms of opioid withdrawal. However, use has been linked to thousands of poisonings, although most have involved use of other drugs. Little is known regarding prevalence and correlates of use in the general U.S. METHODS: Data were examined from the 2019 National Survey on Drug Use and Health, a nationally representative probability sample of non-institutionalized individuals aged ≥12 years in the U.S. (N=56,136). Prevalence and correlates of past-year kratom use were estimated. Data were analyzed in 2020. RESULTS: An estimated 0.7% (95% CI=0.6, 0.8) of individuals in the U.S. have used kratom in the past year. Past-year proxy diagnosis of prescription opioid use disorder was associated with increased odds for kratom use (AOR=3.20, 95% CI=1.38, 7.41), with 10.4% (95% CI=6.7, 15.9) of those with use disorder reporting use. Opioid misuse not accompanied with use disorder was not associated with kratom use. Those reporting past-year cannabis use both with (AOR=4.33, 95% CI=2.61, 7.19) and without (AOR=4.57, 95% CI=3.29, 6.35) use disorder and those reporting past-year cocaine use (AOR=1.69, 95% CI=1.06, 2.69) and prescription stimulant misuse (AOR=2.10, 95% CI=1.44, 3.05) not accompanied with use disorder were at higher odds for kratom use. CONCLUSIONS: Kratom use is particularly prevalent among those with prescription opioid use disorder, but it is also prevalent among people who use other drugs. Research is needed to determine reasons for use and potential dangers associated with adding kratom to drug repertoires.


Assuntos
Estimulantes do Sistema Nervoso Central , Mitragyna , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prevalência
17.
J Pharm Biomed Anal ; 201: 114104, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33964724

RESUMO

The development of a method for the rapid screening of food and drug products for constituents such as mitragynine, the most abundant alkaloid found in Mitragyna speciosa (kratom) plant leaves, has become increasingly important. The use of kratom is said to produce stimulant or narcotic effects and poses risks of addiction, abuse, and dependence, much like other opioids. Direct Analysis in Real Time with thermal desorption mass spectrometry (DART-TD-MS), hand-held mass spectrometry, portable ion mobility spectrometry (IMS), and portable Fourier-transform infrared spectroscopy (FT-IR) were each evaluated as field-deployable screening techniques for the detection of mitragynine in food and drug products. These devices offer the potential for rapid, early detection of mitragynine in suspect products entering the United States through international mail facilities and other ports of entry. Ninety-six kratom products, including capsules, bulk powder, and bulk plant material, were analyzed by either direct sampling of the solid material or by solvent extraction. True and false positive and negative results are reported, based on comparison to results from qualitative screening using gas chromatography with mass spectral detection (GC-MS), liquid chromatography with mass spectral detection (LC-MS), and/or quantitative screening using high-performance liquid chromatography with ultraviolet detection (HPLC-UV), with a discussion of the assessment of each technique for use in the field. Each device demonstrated attributes that would be favorable for use in screening of suspected mitragynine-containing products at places like ports of entry, and simultaneous deployment of two or more of these devices as part of a workflow would be the most effective for rapid screening of these products. This combination of rapid screening orthogonal techniques suited to a non-laboratory environment will allow onsite destruction of products found to contain mitragynine.


Assuntos
Mitragyna , Alcaloides de Triptamina e Secologanina , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Eur J Drug Metab Pharmacokinet ; 46(3): 459-463, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33847897

RESUMO

BACKGROUND AND OBJECTIVES: 7-Hydroxymitragynine (7-HMG) is an oxidative metabolite of mitragynine, the most abundant alkaloid in the leaves of Mitragyna speciosa (otherwise known as kratom). While mitragynine is a weak partial µ-opioid receptor (MOR) agonist, 7-HMG is a potent and full MOR agonist. It is produced from mitragynine by cytochrome P450 (CYP) 3A, a drug-metabolizing CYP isoform predominate in the liver that is also highly expressed in the intestine. Given the opioidergic potency of 7-HMG, a single oral dose pharmacokinetic and safety study of 7-HMG was performed in beagle dogs. METHODS: Following a single oral dose (1 mg/kg) of 7-HMG, plasma samples were obtained from healthy female beagle dogs. Concentrations of 7-HMG were determined using ultra-performance liquid chromatography coupled with a tandem mass spectrometer (UPLC-MS/MS). Pharmacokinetic parameters were calculated using a model-independent non-compartmental analysis of plasma concentration-time data. RESULTS: Absorption of 7-HMG was rapid, with a peak plasma concentration (Cmax, 56.4 ± 1.6 ng/ml) observed within 15 min post-dose. In contrast, 7-HMG elimination was slow, exhibiting a mono-exponential distribution and mean elimination half-life of 3.6 ± 0.5 h. Oral dosing of 1 mg/kg 7-HMG was well tolerated with no observed adverse events or significant changes to clinical laboratory tests. CONCLUSIONS: These results provide the first pharmacokinetic and safety data for 7-HMG in the dog and therefore contribute to the understanding of the putative pharmacologic role of 7-HMG resulting from an oral delivery of mitragynine from kratom.


Assuntos
Mitragyna/química , Modelos Biológicos , Alcaloides de Triptamina e Secologanina/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cães , Feminino , Meia-Vida , Folhas de Planta , Alcaloides de Triptamina e Secologanina/administração & dosagem , Alcaloides de Triptamina e Secologanina/toxicidade , Espectrometria de Massas em Tandem , Distribuição Tecidual
19.
J Emerg Nurs ; 47(4): 551-556.e1, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33863579

RESUMO

Kratom ingestion for its psychotropic effect or to self-treat opioid withdrawal symptoms has increased over the last 10 years in the United States. Although mild adverse effects have been observed in users, reports of respiratory failure and shock after kratom consumption remain rare. In this case, a 35-year-old man initially presented to the emergency department with profound circulatory shock, metabolic acidosis, hypoxia, and symptoms of autonomic nervous system dysfunction. The patient required vasopressor support, multiregimen sedation and rapid sequence intubation, mechanical ventilation, and emergent hemodialysis. Within 72 hours, the patient's condition stabilized, and he was extubated. The patient reported regular consumption of large quantities of kratom as well as injection of heroin and cocaine. In this report, a rare clinical presentation after kratom ingestion is described.


Assuntos
Serviços Médicos de Emergência , Mitragyna , Síndrome de Abstinência a Substâncias , Adulto , Analgésicos Opioides/uso terapêutico , Ingestão de Alimentos , Humanos , Síndrome de Abstinência a Substâncias/tratamento farmacológico
20.
J Investig Med High Impact Case Rep ; 9: 23247096211005069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33764201

RESUMO

Kratom mainly grows in Southeast Asia. It is widely used for pain management and opioid withdrawal, which is available online for cheaper prices. Alkaloids extracted from kratom such as mitragynine and 7-hydroxy mitragynine exhibit analgesic properties by acting through µ receptors. Commonly reported side effects of kratom include hypertension, tachycardia, agitation, dry mouth, hallucinations, cognitive and behavioral impairment, cardiotoxicity, renal failure, cholestasis, seizures, respiratory depression, coma, and sudden cardiac death from cardiac arrest. Rhabdomyolysis is a less commonly reported lethal effect of kratom. Limited information is available in the literature. In this article, we present a case of a 45-year-old female who is overdosed with kratom and presented with lethargy, confusion, transient hearing loss, and right lower extremity swelling and pain associated with weakness who was found to have elevated creatinine phosphokinase. She was diagnosed with rhabdomyolysis, compartment syndrome, multiorgan dysfunction including acute kidney injury, liver dysfunction, and cardiomyopathy. She underwent emergent fasciotomy and required hemodialysis. Her renal and liver function subsequently improved. We described the case and discussed pharmacology and adverse effects of kratom toxicity with a proposed mechanism and management. We conclude that it is essential for emergency physicians, internists, intensivists, cardiologists, and nephrologists to be aware of these rare manifestations of kratom and consider a multidisciplinary approach.


Assuntos
Overdose de Drogas/complicações , Perda Auditiva , Insuficiência Cardíaca , Mitragyna/envenenamento , Extratos Vegetais/envenenamento , Rabdomiólise , Perda Auditiva/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Rabdomiólise/induzido quimicamente
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