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1.
J Dual Diagn ; 20(2): 87-97, 2024.
Article in English | MEDLINE | ID: mdl-38153407

ABSTRACT

OBJECTIVE: Despite kratom impacting neurobiological systems involved in psychiatric disorders, little is known about the prevalence of use among patients with severe psychopathologies. Here, we investigated the prevalence of kratom use, motives for use, and the clinical associations among inpatients with severe psychiatric disorders. METHODS: A total of 578 patients, aged 18 to 65, were evaluated by New Hampshire Hospital's Addiction Services from January 1, 2020, to February 28, 2022. The study collected demographic information and used chi-square tests, multivariable logistic regression, and subgroup analyses with 95% confidence intervals to examine trends among kratom users. A receiver operating characteristic curve analysis was also conducted. All statistical tests were performed using IBM SPSS Version 28.0.1. RESULTS: Of the patients assessed, 2.2% (n = 13) reported using kratom. The reasons for kratom use were managing withdrawal symptoms (15.4%), maintaining sobriety and reducing cravings for opioids (53.8%), improving focus and concentration (30.8%), alleviating low moods (38.5%), and managing pain (15.4%). Compared to non-kratom users, the only factor with a fair to good association with kratom use is postsecondary education (Area Under Curve, AUC = 0.77). CONCLUSIONS: Prevalence of kratom use among patients with serious mental illness at our site aligns with that reported in the general population. Users often cite self-management of cravings and sobriety from opioids, as well as treatment of low mood states, as motivations for consumption. While observations suggest a possible association between kratom use and individuals with post-secondary education, multiple substance use, and experience of substance-induced psychosis or mood disorders, it is essential to interpret these links cautiously until further rigorous studies are carried out to substantiate these findings.


Subject(s)
Mitragyna , Substance Withdrawal Syndrome , Substance-Related Disorders , Humans , Mitragyna/adverse effects , Inpatients , Prevalence , Substance-Related Disorders/complications , Substance-Related Disorders/epidemiology , Substance-Related Disorders/drug therapy , Substance Withdrawal Syndrome/complications , Substance Withdrawal Syndrome/epidemiology , Substance Withdrawal Syndrome/drug therapy , Analgesics, Opioid/therapeutic use
2.
Am J Drug Alcohol Abuse ; 48(5): 509-528, 2022 09 03.
Article in English | MEDLINE | ID: mdl-36001875

ABSTRACT

Background: Kratom (Mitragyna speciosa Korth.) products are increasingly endorsed for self-management of multiple ailments, including as opioid substitution. The FDA has expressed that there is no evidence to indicate that this botanical is safe or effective for any medical use.Objective: We systematically review the current state of the literature concerning the impact of kratom and its alkaloids in all paradigms that involve opioids.Methods: A keyword search of online literature databases identified 16 preclinical studies, 25 case reports, and 10 observational studies meeting our pre-selected criteria.Results: All rodent models support alkaloids' action on opioid receptors, translating in their ability to mitigate opioid withdrawal. Some studies found mitragynine (MG) to have less reinforcing properties than morphine, and possessing tolerance-sparing properties when coadministered with morphine. Two studies that assessed 7-hydroxymitragynine (7OHMG) found it to substitute for morphine with potential for tolerance and dependence. Aside from addiction development, case reports outline a variety of confounding toxicities. Ten surveys of users, some conducted with assistance from pro-kratom lobbying organizations, find a high self-reported efficacy as an opioid substitute, with minimal reported adverse effects.Conclusion: With no reported controlled human clinical trials, in the light of rising concerns surrounding kratom's liabilities, there is insufficient evidence to allow any conclusions to be drawn. Case reports and observational studies carry significant bias toward harm and efficacy, respectively. Existing animal studies are heterogeneous in methodology and ultimately findings, with concern for interspecies variability and human translatability. Further research should investigate the safety and efficacy of using kratom alkaloids as opioid substitutes.


Subject(s)
Mitragyna , Analgesics, Opioid/adverse effects , Analgesics, Opioid/therapeutic use , Animals , Harm Reduction , Humans , Morphine , Receptors, Opioid
3.
Pain Manag Nurs ; 23(6): 693-702, 2022 12.
Article in English | MEDLINE | ID: mdl-36261305

ABSTRACT

BACKGROUND: Pain intensity remains a primary focus clinically for sickle cell disease pain assessment despite the fact that pain quality and pain location and distribution are critical for clinical diagnosis and treatment of its etiology. However, in part because of measurement issues, scant evidence is available about pain location or its relationship to intensity and quality in adults with SCD. AIM: Our study aim was to examine sickle cell disease pain location for relationships with pain quality and intensity measured in outpatient and inpatient settings. METHODS: We used an existing longitudinal dataset prospectively collected with the valid and reliable tablet-based PAINReportItⓇ. Adults with sickle cell disease (n = 99) reported pain location, intensity, and quality during a routine outpatient clinic visit and again during a subsequent hospitalization. From their digital body outline drawings and using the ImageJ software, we computed the pain-affected body surface area. With Pearson's correlations and paired t tests, we examined relationships between pain-affected body surface area and other pain variables across outpatient and inpatient visits. RESULTS: The mean pain-affected body surface area was 14.4% ± 15.0% of the total body surface area for outpatient visits (min-max: 0.0%-90.2%) and 13.5% ± 14.7% (min-max: 0.0%-73.0%) for inpatient stay. Pain-affected body surface area was positively correlated with pain quality scores for both visits but not significantly correlated with pain intensity at either visit. Compared with the outpatient visit, mean pain intensity for inpatient stay was higher (p < .001); pain quality (p = .12) and pain-affected body surface area (p = .60) did not differ significantly between visits. CONCLUSIONS: Unknown is the explanation for pain-affected body surface area association with SCD pain quality but not pain intensity at outpatient and inpatient visits. Additional research is warranted to explore these findings and examine the clinical utility of pain-affected body surface area for chronic sickle cell disease pain and acute sickle cell disease crisis pain.


Subject(s)
Acute Pain , Anemia, Sickle Cell , Chronic Pain , Adult , Humans , Anemia, Sickle Cell/complications , Pain Measurement , Pain Management , Chronic Pain/drug therapy
4.
Am J Drug Alcohol Abuse ; 48(6): 684-694, 2022 11 02.
Article in English | MEDLINE | ID: mdl-35767669

ABSTRACT

Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.


Subject(s)
Mitragyna , Humans , Female , Adult
5.
Am J Drug Alcohol Abuse ; 48(4): 433-444, 2022 07 04.
Article in English | MEDLINE | ID: mdl-35389321

ABSTRACT

Background: Kratom (Mitragyna speciosa Korth.) use outside of Southeast Asia has increased over the past decade. Objectives: This investigation clarifies kratom's role in perceived well-being, overall health, and temporal correlation with drug use to understand kratom's role in the self-treatment of substance use disorders (SUDs). Methods: Between July 2019 and July 2020 an anonymous, cross-sectional, online survey was taken by 7,381 people who use kratom (PWUK) recruited through social media and other online resources. This included an assessment of (a) the relationship between self-reported overall health, concomitant use of drugs of misuse, and demographics; (b) the perceived effectiveness of kratom in self-treating diagnosed health conditions or symptoms; (c) the profile of PWUK primarily for drug dependence, pain, and mood or mental health conditions based on demographics. Results: A total of 5,152 valid responses (45.9% females/53.7% males) were collected. Kratom was primarily used for self-treating pain (73.0%) and improving emotional or mental health conditions (42.2%) without clinical supervision. Those with a SUD (synthetic opioids, methadone, benzodiazepines, or heroin) used kratom after discontinuing illicit or other drugs (94.8%). The primary substances taken before or concomitantly with kratom were cannabis, cannabidiol, benzodiazepines, or kava. PWUKs report a dose-dependent benefit for alleviating pain and relieving negative moods. Adverse effects were primarily gastrointestinal, typically at high (>5 g/dose) and frequent (>22 doses/week) dosing. Conclusions: Kratom was primarily used as a harm-reduction agent for SUDs and self-treatment of chronic conditions. Healthcare professionals need better information about kratom, its potential adverse effects, and clinically significant drug interactions.


Subject(s)
Mitragyna , Substance-Related Disorders , Benzodiazepines , Cross-Sectional Studies , Female , Humans , Male , Motivation , Pain , Self Report , Substance-Related Disorders/complications
6.
Subst Abus ; 43(1): 865-877, 2022.
Article in English | MEDLINE | ID: mdl-35179453

ABSTRACT

Background: Kratom, a tree native to Southeast Asia, is increasingly used in Western countries for self-treatment of pain, psychiatric disorders, and mitigation of withdrawal symptoms from drugs of abuse. Because kratom is solely supplied from its native locations, supply shortages during the COVID-19 pandemic may impact the availability of preparations and hence force consumers to change their patterns of use. The aim of this study was to understand if and how COVID-19 was influencing kratom purchasing and use. Methods: Additional questions specific to kratom availability and changes in use during COVID-19 were added to an international online survey with responses collected between January and July 2020. During the same period, kratom-related social media posts to Twitter, Reddit, and Bluelight were analyzed for themes similar to the survey questions. Results: The survey results indicated no changes in kratom use patterns although the sample size was relatively small (n = 70) with younger consumers reporting a potential issue in obtaining their desired products from their usual sources. The survey respondents identified primarily as non-Hispanic whites (87.1%). Social media themes revolved primarily around quitting kratom during COVID-19, misinformation about the effects of kratom on COVID-19, and other non-COVID-related discussions. While some consumers may increase their kratom dose because of additional stress, a majority of discussions centered around reducing or rationing kratom due to COVID-19 or a perceived dependence. Access to quality kratom products was also a major discussion topic on social media. Conclusions: Kratom use patterns did not change due to COVID-19 but consumers were concerned about potential product shortages and resulting quality issues. Clinicians and public health officials need to be informed and educated about kratom use as a potential mitigation strategy for substance use disorders and for self-treatment of pain.


Subject(s)
COVID-19 , Mitragyna , Social Media , Humans , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
7.
Subst Abus ; 43(1): 1221-1224, 2022.
Article in English | MEDLINE | ID: mdl-35657649

ABSTRACT

This Letter to the Editor is a response to Broyan and colleagues who recently published a Case Report presenting data on 28 patients in the United States who identified kratom as their primary substance of use and who were subsequently induced on buprenorphine/naloxone for a reported diagnosis of kratom use disorder. We applaud the authors for helping to advance the science on kratom and recognize the difficulties in conducting kratom-related clinical assessment and research. However, a number of inconsistences and generalizations were identified in this Case Report, which also lacked some critical context. Importantly, such inconsistencies and generalizations can be observed throughout kratom-specific case reports. We feel this is now an important opportunity to highlight these issues that are present in the Broyan and colleagues Case report but emphasize that they are not unique to it. We do this with the hope that by acknowledging these issues it can help inform editors, clinicians, and researchers who may not be familiar with kratom and, as a result of this unfamiliarity, may inadvertently present findings in a manner that could confuse readers and even misinform clinical researchers and practitioners.


Subject(s)
Mitragyna , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Buprenorphine, Naloxone Drug Combination/therapeutic use , Humans , Opioid-Related Disorders/diagnosis , Opioid-Related Disorders/drug therapy , United States
8.
Yale J Biol Med ; 93(2): 283-289, 2020 06.
Article in English | MEDLINE | ID: mdl-32607089

ABSTRACT

Mitragyna speciosa, otherwise known as kratom, is a plant in the coffee family (Rubiaceae) native to Southeast Asia and Thailand whose leaves have been shown to cause opioid-like and stimulant responses upon ingestion. The major pharmacologically active compounds present in kratom, mitragynine and 7-hydroxymitragynine (7-HMG), are both indole alkaloids and are responsible for its opioid-like activity. While kratom is most commonly known for its affinity for mu-opioid receptors, research has shown one of its active components has effects on the same receptors to which some antipsychotics bind, such as D2 dopamine, serotonin (5-HT2C and 5-HT7), and alpha-2 adrenergic receptors displaying possible indications of kratom to be used as both antipsychotics and antidepressants. Although studies to evaluate this effect are still lacking, several online and in-person surveys note relief of depression and anxiety symptoms among those who consume kratom products, and in fact identify it as a common reason for consumption. This then highlights the dire need for further research to be conducted on kratom, its mechanism of action and the constituents that elicit these antidepressant, anxiolytic, and antipsychotic properties.


Subject(s)
Antidepressive Agents/pharmacology , Antipsychotic Agents/pharmacology , Behavioral Symptoms/drug therapy , Mitragyna , Biological Products/pharmacology , Humans , Indole Alkaloids/pharmacology , Receptors, Opioid , Secologanin Tryptamine Alkaloids/pharmacology , Treatment Outcome
9.
Prev Med ; 128: 105851, 2019 11.
Article in English | MEDLINE | ID: mdl-31647958

ABSTRACT

Kratom use appears to be increasing across the United States, increasing attention to deaths in which kratom use was detected. Most such deaths have been ascribed to fentanyl, heroin, benzodiazepines, prescription opioids, cocaine and other causes (e.g., homicide, suicide and various preexisting diseases). Because kratom has certain opioid-like effects (e.g., pain relief), and is used by some people as a substitute for opioids for pain or addiction, kratom has been compared to "narcotic-like opioids" (e.g., morphine) with respect to risk of death despite evidence that its primary alkaloid, mitragynine, carries little of the signature respiratory depressing effects of morphine-like opioids. This commentary summarizes animal toxicology data, surveys and mortality data associated with opioids and kratom to provide a basis for estimating relative mortality risk. Population-level mortality estimates attributed to opioids as compared to kratom, and the per user mortality risks of opioids as compared to kratom are provided. By any of our assessments, it appears that the risk of overdose death is >1000 times greater for opioids than for kratom. The limitations of the mortality risk estimate warrants caution in individuals with unknown factors such as use of other substances and medications, or other preexisting conditions. More research on kratom safety and risks is needed, as is regulation of commercial kratom products to ensure that consumers are informed by FDA labeling and that kratom products are not contaminated or adulterated with other substances.


Subject(s)
Analgesics, Opioid/adverse effects , Analgesics, Opioid/therapeutic use , Drug Overdose/mortality , Mitragyna/chemistry , Opioid-Related Disorders/mortality , Pain/drug therapy , Plant Extracts/adverse effects , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Risk Factors , United States/epidemiology
10.
Hum Psychopharmacol ; 34(5): e2709, 2019 09.
Article in English | MEDLINE | ID: mdl-31347212

ABSTRACT

OBJECTIVE: Kratom preparations have raised concerns of public health and safety in the United States. This paper analyzed the patterns and predictors of kratom use by four U.S. regions according to the U.S. Census. METHOD: An anonymous cross-sectional online survey yielded 8,049 valid responses. The data were categorised by regions (Northeast, South, Midwest, and West) and analyzed for the following predictors: age, gender, marital status, ethnicity, employment status, insurance coverage, education, and household income. RESULTS: After adjusting for state population, the survey response rates were highest from Oregon, Idaho, and Florida. Kratom use was significantly lower for both prescription drug dependency and acute or chronic pain in the Northeast region than the rest of the country. Multiple logistic regression models found that gender, employment, and education were significant on the regional level. Higher education was associated with lower kratom use for an illicit drug dependency (p = .002) independent of region whereas men were less likely to use kratom for acute or chronic pain in the Northeast (p < .001) but more likely in the Midwest (p = .041). CONCLUSIONS: The regional pattern of kratom use differed from opioid use data in both demographics and trend direction warranting further investigation.


Subject(s)
Mitragyna , Adolescent , Adult , Aged , Cross-Sectional Studies , Employment , Female , Humans , Logistic Models , Male , Middle Aged , Pain/drug therapy , Sex Characteristics , Surveys and Questionnaires , United States , Young Adult
11.
Subst Use Misuse ; 54(14): 2284-2289, 2019.
Article in English | MEDLINE | ID: mdl-31347441

ABSTRACT

Background: Mitragyna speciosa (Korth.) or kratom is an indigenous medicinal plant of Southeast Asia. Kratom is widely reported to have dose-dependent effects based on available literature, but to our knowledge, this has not been established conclusively. Objective: This study sought to evaluate if kratom use produces dose-dependent effects, with a stimulant effect at low doses and a sedative effect at high doses, in a sample of regular kratom users. Methods: A total of 63 regular kratom users participated in this cross-sectional study. The Brief-Biphasic Alcohol Effects Scale (B-BAES) was used to determine subjects self-report kratom use experiences. Results: Almost all in the sample were male (98%, n = 62/63), and the majority of subjects were Malays (94%, n = 59/63). The mean age of the subjects in the sample was 43.8 years (SD = 12.1). Seventy-five percent (n = 47/63) have >5 years kratom use history, and 65% (n = 41/63) consumed >3 glasses of kratom daily. Results from first test showed no significant difference in the stimulant (t61 =0.371, p < .331) and sedative effects (t61 =502, p < .759) between those who consumed >3 glasses a day or less than this amount, regardless of duration of use. In the second test, no significant differences in the mean scores were found among those who consumed >3 glasses daily or less than this amount among short-term or long-term uses. Conclusions: Daily kratom use produced both stimulant and sedative effects but they were not statistically significantly associated with the dose consumed, both among short-term and long-term users in our sample.


Subject(s)
Central Nervous System Stimulants/administration & dosage , Hypnotics and Sedatives/administration & dosage , Mitragyna , Adult , Cross-Sectional Studies , Dose-Response Relationship, Drug , Female , Humans , Malaysia , Male , Middle Aged , Self Report
12.
Phytother Res ; 32(5): 796-810, 2018 May.
Article in English | MEDLINE | ID: mdl-29417644

ABSTRACT

The indiscriminate use of herbal medicines to prevent or to heal diseases or even the use for questionable purposes such as weight loss has received both interest and scrutiny from the scientific community and general public alike. An increasing number of women put their own and the unborn child's health at risk due to a lack of knowledge about the phytochemical properties and adequate use of herbal medicine (phytomedicines or herbal supplements) and lack of communication with their healthcare provider. The purpose of this narrative review was to summarize the use of herbal medicines during pregnancy and their potential toxic effects to highlight the importance of caution when prescribing herbal medicines or supplements for women, because, in addition to suffering interactions and a great amount of information obtained in preclinical predictive studies, assessment of nephrotoxicity, neurotoxicity, hepatotoxicity, genotoxicity, and teratogenicity of traditional medicinal herbs still remains scarce in the clinical setting.


Subject(s)
Herbal Medicine , Phytotherapy , Pregnancy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Herbal Medicine/methods , Humans , Phytotherapy/adverse effects , Phytotherapy/methods , Plants, Medicinal/adverse effects , Plants, Medicinal/physiology , Pregnancy Complications/chemically induced , Pregnancy Complications/epidemiology , Risk Factors , Women's Health
13.
Int J Legal Med ; 130(1): 127-38, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26511390

ABSTRACT

Mitragyna speciosa (Rubiaceae), commonly known as kratom, is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. In recent years, kratom has gained popularity for use as a recreational drug across the globe. Relatively new to the illicit market and used in a manner different from its traditional applications, preparations of kratom are touted by many as a safe and legal psychoactive product that improves mood, relieves pain, and may provide benefits in opiate addiction. Available literature was reviewed for M. speciosa via PubMed, Google Scholar, CINAHL, and EBSCO to summarize its traditional uses, phytochemical composition, pharmacology and toxicology of proposed active constituents, and potential for misuse and abuse. Research has demonstrated that both stimulant and sedative dose-dependent effects do exist, but a growing concern for the drug's effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are said to have been caused by extracts of the plant. The main active alkaloid substances in kratom, mitragynine and 7-hydroxymitragynine, present with a range of CNS stimulant and depressant effects mediated primarily through monoaminergic and opioid receptors. Recently, Palm Beach County, located in the southeastern corridor of Florida, has considered regulating kratom due to public safety concerns following the death of a young adult. At the local, state, and even federal levels, governments are now being confronted with the task of determining the safety and the possible regulation of kratom extracts. There are currently no standard analytical screening techniques for mitragynine and its metabolites following ingestion limiting its detection to more sophisticated techniques like liquid chromatography-mass spectrometry to determine kratom use. The growing concern of the abuse potential of kratom requires careful evaluation of its benefits and potential toxicities.


Subject(s)
Illicit Drugs/pharmacology , Mitragyna/chemistry , Psychotropic Drugs/pharmacology , Drug and Narcotic Control , Forensic Toxicology , Half-Life , Humans , Illicit Drugs/chemistry , Molecular Structure , Plant Extracts/chemistry , Plant Leaves/chemistry , Psychotropic Drugs/chemistry , Substance-Related Disorders/complications , United States , United States Food and Drug Administration
14.
Mini Rev Med Chem ; 24(3): 289-299, 2024.
Article in English | MEDLINE | ID: mdl-37489781

ABSTRACT

Alongside the prescription of commonly used antivirals, such as acyclovir, remdesivir, oseltamivir, and ciprofloxacin, the most efficient way to prevent or treat communicable diseases is by vaccination. Vaccines have been the most efficient way to prevent or treat highly transmissible infectious agents, such as Ebola, Anthrax, and Dengue Fever. Most epidemics of these highly transmissible infectious agents occur in places, such as South America, Central America, Tropical Asia, and Africa, where the availability of resources and access to adequate healthcare are limited. However, recent events in history have proven that even with access to resources and proper healthcare, those in firstworld countries are not invincible when it comes to infectious diseases and epidemics. The Ebola virus outbreak in West Africa highlighted the gaps in therapeutic advancement and readiness and led to the rapid development of novel vaccine approaches. Viral vectors, in the case of the Ebola vaccine the Vesicular Stomatitis Virus (VSV), can be safely used to activate or initiate the innate adaptive immune response to protect against viral infection. When developed properly and with extensive study, novel vaccine approaches allow physicians and health experts to control the rate at which viruses spread or prevent transmission. This review will discuss the advantages of viral vector vaccines, their chemistry and development, and the pathophysiology of the Ebola virus to develop advantageous and efficacious treatments.


Subject(s)
Communicable Diseases , Ebola Vaccines , Ebolavirus , Hemorrhagic Fever, Ebola , Viral Vaccines , Animals , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/prevention & control , Vesiculovirus , Zoonoses
15.
Subst Abuse Rehabil ; 15: 43-57, 2024.
Article in English | MEDLINE | ID: mdl-38585160

ABSTRACT

Nalmefene hydrochloride was first discovered as an opioid antagonist derivative of naltrexone in 1975. It is among the most potent opioid antagonists currently on the market and is differentiated from naloxone and naltrexone by its partial agonist activity at the kappa-opioid receptor which may benefit in the treatment of alcohol use disorder. Oral nalmefene has been approved in the European Union for treatment of alcohol use disorder since 2013. As of 2023, nalmefene is available in the United States as an intranasal spray for reversal of opioid overdose but is not approved for alcohol or opioid use disorder as a maintenance treatment. The substantially longer half-life of nalmefene and 5-fold higher binding affinity to opioid receptors makes it a superior agent over naloxone in the reversal of high potency synthetic opioids like fentanyl and the emerging nitazenes. Nalmefene presents with a comparable side effect profile to other opioid antagonists and should be considered for further development as a maintenance treatment for opioid and other substance use disorders.

16.
Front Public Health ; 12: 1416689, 2024.
Article in English | MEDLINE | ID: mdl-38873312

ABSTRACT

Substance use disorders contribute to considerable U.S. morbidity and mortality. While effective pharmacotherapy options are available to treat opioid and alcohol use disorders, for a variety of reasons, many patients lack access to treatment or may be reluctant to seek care due to concerns such as perceived stigma or a current lack of desire to completely curtail their substance use. Furthermore, treatment options are limited for patients with stimulant or polysubstance use disorders. Thus, there is considerable need to expand the substance use disorder harm reduction armamentarium. Kratom (Mitragyna speciosa Korth.) is an herbal substance that can produce both opioid and stimulant-like effects, and its use in the US is growing. Though there are concerns regarding adverse effects, dependence risk, and limited regulation of its manufacturing and sale, the pharmacology of kratom and early preclinical studies suggest a potential role as a harm reduction agent for various substance use disorders, and it has historically been used in Southeast Asia for such purposes. The goal of this review is to describe kratom's history of use, pharmacology, and early pre-clinical and observational research regarding its therapeutic potential in opioid use disorder, as well as alcohol, stimulant, and polysubstance use disorders, while also highlighting current concerns around its use, existing gaps in the literature, and directions for future research.


Subject(s)
Harm Reduction , Mitragyna , Substance-Related Disorders , Mitragyna/chemistry , Humans , Substance-Related Disorders/prevention & control , Plant Extracts/therapeutic use
17.
J Addict Med ; 18(3): 306-312, 2024.
Article in English | MEDLINE | ID: mdl-38441236

ABSTRACT

OBJECTIVES: Kratom leaf products are increasingly consumed in the United States, with many consumers reporting they experience beneficial effects from kratom use. However, there is a growing concern for kratom's potential to result in dependence when used regularly. As such, we sought to assess, using Diagnostic and Statistical Manual of Mental Disorders , (DSM-5) , diagnostic criteria for substance use disorder, the prevalence of "kratom use disorder" (KUD) among kratom consumers. METHODS: Our cross-sectional study used an online, anonymous survey between February and May 2023. Through nonprobability sampling, we recruited people older than 18 years who currently consume kratom. Participants were asked about their kratom consumption patterns, adverse effects perceived to stem from kratom consumption, comorbid diagnoses, and components for a DSM-5 , substance use disorder, adapted for kratom. RESULTS: Among the total sample ( N = 2061), KUD criteria were met by 25.5% of participants ( n = 525); the most commonly reported symptoms were tolerance ( n = 427, 81.3%) and withdrawal ( n = 357, 68.0%). After adjusting for age, gender, daily frequency of kratom consumption, and history of either a substance use disorder or a mental health condition, those with a concurrent diagnosis of another substance use disorder had 2.83 times higher odds of meeting KUD criteria (95% CI, 2.19-3.67) compared with those without one. CONCLUSIONS: In this large cross-sectional study, most participants who met the criteria for a KUD diagnosis were categorized as having a mild or moderate KUD. Individual characteristics associated with KUD were related to being male, young, consuming kratom frequently, and having psychiatric and substance use disorder comorbidities.


Subject(s)
Mitragyna , Substance-Related Disorders , Humans , Female , Male , Cross-Sectional Studies , Adult , Substance-Related Disorders/epidemiology , Mitragyna/adverse effects , Prevalence , Middle Aged , Young Adult , United States/epidemiology , Adolescent , Aged , Comorbidity , Surveys and Questionnaires
18.
Front Pharmacol ; 15: 1403140, 2024.
Article in English | MEDLINE | ID: mdl-38887550

ABSTRACT

Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom's benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product.

19.
Drug Alcohol Depend ; 260: 111329, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38788532

ABSTRACT

BACKGROUND: Kratom products are widely used in the United States, with inadequate understanding of how dosing amounts/frequencies relate to outcomes. METHODS: Between July-November 2022, we enrolled 395 active US adult kratom consumers into a remote study with a baseline survey. We examined self-reported typical dose amounts and frequencies across people and product types, and their associations with outcomes: multiple regression was used to examine whether amounts and frequencies (doses/day) were associated with acute effects, withdrawal symptoms, scores on the Subjective Opioid Withdrawal Scale (SOWS), and addiction (operationalized as DSM-5-based symptoms of kratom-use disorder, KUD). RESULTS: Participants were 54.9% male, aged 38.1 on average, and 81.3% White. Mean length of kratom use was 5.7 years. Most (95.9%) reported regularly using whole-leaf kratom products; 16 (4.1%) reported regular extract use. SOWS scores were mild to moderate on average (13.5, SD 11.9). KUD symptom counts were mostly in the mild/moderate range (80.7%). Withdrawal and KUD symptoms were more closely associated with dose frequency than dose amount. Men reported more acute effects, withdrawal symptoms with cessation, and KUD symptoms than women. CONCLUSIONS: Greater dose amount and frequency were systematically related to the number of withdrawal symptoms upon cessation and to KUD symptoms; the relationship was stronger for dose frequency than amount. Men may have more acute effects and more withdrawal and KUD symptoms than women. Although kratom may be used nonproblematically by some consumers, physical dependence (tolerance, withdrawal, or use to avoid withdrawal) and KUD become more likely with increasing dose frequency.


Subject(s)
Diagnostic and Statistical Manual of Mental Disorders , Mitragyna , Substance Withdrawal Syndrome , Humans , Male , Female , Adult , Mitragyna/chemistry , Middle Aged , Substance Withdrawal Syndrome/diagnosis , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , Young Adult , Dose-Response Relationship, Drug
20.
J Addict Med ; 18(6): 719-722, 2024.
Article in English | MEDLINE | ID: mdl-39012004

ABSTRACT

OBJECTIVES: To estimate lifetime, past-year, and past-month prevalence of kratom, cannabis, and cannabidiol-only product use among adults 18 years and older in the United States, using 2 independent datasets. METHODS: Utilizing ( a ) the 2022 National Survey on Drug Use and Health (NSDUH) and ( b ) a 2022 online national convenience sample of adults who use kratom regularly (from our research group at the National Institute on Drug Abuse [NIDA]), we examined key demographic information as well as lifetime, past-year, and past-month substance use and preferences. RESULTS: Among the full sample of adults from the 2022 NSDUH, the prevalence of lifetime use was 49.69% for cannabis, 34.09% for cannabidiol-only products, and 1.93% for kratom. When solely examining participants who have used kratom, both independent datasets showed higher proportions of cannabis use over the lifetime-92.81% (95% confidence interval: 90.31-95.31) in the NSDUH subset and 92.16% (95% confidence interval: 89.37-94.95) in our NIDA sample. CONCLUSIONS: Our study demonstrates that people are co-using kratom with cannabis and/or cannabidiol-only products at the same time or during the same time period, though more research is needed to understand people's motivations and practices for such co-use. Co-use might result in herb-herb interactions that may impact research findings and clinical outcomes for people who use kratom.


Subject(s)
Cannabinoids , Mitragyna , Humans , United States/epidemiology , Adult , Male , Female , Young Adult , Adolescent , Middle Aged , Prevalence , Cannabidiol
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