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A Preliminary Inventory of Kratom (Mitragyna Speciosa) Products and Vendors on the Darknet and Cryptomarkets
... Psychopharmacology Kratom use has also expanded to Western countries, leading to a wide availability of kratom products (e.g., powder, capsules, tablets) online and in specialty shops (Hillebrand et al. 2010;Prevete et al. 2024;Prozialeck et al. 2012;Williams and Nikitin 2020). The main motivations for using kratom include recreational purposes and self-treatment of various mental and physical health conditions (Bath et al. 2020;Coe et al. 2019;Grundmann et al. , 2023Smith et al. 2024a). ...
... Given that there had been no studies that assessed synthetic mitragynine in naive users, we opted to focus on low doses of mitragynine, rather than high doses that are sometimes taken by chronic users. The current dose range however overlaps with those currently expected in a variety of kratom products that are sold for recreational use (Prevete et al. 2024) and with those in kratom products that are currently under development for medical applications (Huestis et al. 2024). ...
Rationale
Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom (Mitragyna Speciosa), there is a lack of clinical trials in humans.
Objectives
This phase 1 study aimed to evaluate mitragynine’s safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance.
Methods
A placebo-controlled, single-blind, within-subjects study was conducted in two parts. In part A, eight healthy human volunteers received placebo and three doses of mitragynine (5, 10, and 20 mg) in a sequential dosing scheme, on separate days. In part B, a second group of seven volunteers received placebo and 40 mg of mitragynine. Vital signs, subjective drug experience, neurocognitive function, and pain tolerance were measured at regular intervals for 7 h after administration.
Results
Overall, mitragynine did not affect most of the outcome measures at any dose. Yet, the lowest dose (5 mg) of mitragynine increased subjective ratings of arousal and attention, accuracy in a sustained attention task, and motor inhibition. The highest dose (40 mg) of mitragynine increased subjective ratings of amnesia and produced mild psychopathological symptoms. Mitragynine did not significantly affect vital signs, and only mild, transient side effects were reported.
Conclusion
The present study suggests that low doses (5–10 mg) of mitragynine may cause subjective feelings of stimulation and enhance attention, while the highest dose (40 mg) may cause inhibitory feelings of amnesia and distress. Mitragynine doses up to 40 mg were well tolerated in this group.
... Furthermore, young people are undoubtedly at higher risk for NPS consumption, substances that may have other types of markets, such as the web or the darknet, which are more accessible to young people [38]. ...
People diagnosed with substance use disorder (SUD) might represent a high‐risk subpopulation for New Psychoactive Drugs (NPS) consumption, and hair analysis offers a unique perspective to assess drug prevalence in this population. The present study aims to assess the prevalence of NPS and their co‐consumption with traditional drugs of abuse (DoA) in individuals diagnosed with SUD. Hair samples from patients under care at the addiction treatment service of Bologna, Italy, for a diagnosed SUD, were collected during 2023 and analyzed by ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC–MS/MS), using a previously validated method. Among the 88 patients included, 95.5% tested positive for at least one substance, of which 88.1% for traditional DoA only, and 11.9% for NPS in addition to DoA. Among the positive samples, patients were found positive for more than two drugs in 67.9% of cases. The combination of DoA and NPS was more frequent in the younger age group (<21–30 years old, compared to 31–70, p = 0.025). Ketamine was detected in 8.0% of all samples, with mean hair levels 49.68 pg/mg (ranging 8.55–81.90 pg/mg) and was frequently accompanied by cocaine (85.7% of cases). Fentanyl was detected in 3.4% of all samples, while, among NPS, buphedrone was the only one detected. Our retrospective study highlights that the consumption of NPS is relatively low compared to other vulnerable or high‐risk populations. However, the prevalence of polydrug consumption and the high rate of ketamine–cocaine combination warrant careful monitoring even in this population.
Traditionally used in Southeast Asia for common ailments, kratom (Mitragyna speciosa) is increasingly being adopted in other regions for the self-treatment of pain, mental health issues such as anxiety, depression, and dependence or managing the withdrawal symptoms linked to stimulants/sedatives or other substances in absence of clinical supervision. To gain better insight into the experiences and the motivations underlying kratom use, previous studies have analyzed material shared among users on social media. However, these investigations often employed manual labeling and categorizations, which are time-consuming and do not allow the investigation of large samples. The present work utilized a natural language processing approach (BERTopic) to extract prominent topics of discussion from kratom-related Reddit posts made between 2010 to 2023 (n = 188,139 posts). Dynamic Topic Modeling was also implemented to analyze how discussions about these topics evolved over time. From the results, users discussed topics including usage for substance use disorder recovery (e.g., suboxone), drug testing, consumption methods, logistic issues (e.g., bringing kratom on flights, receiving kratom via mail), tapering off the use of kratom, and providing support to others who are in the process of quitting kratom. The current study supports the need of clinical trials as well as new ecological insights into experiences of kratom users, while supporting the implementation of new policies to regulate its usage.
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.
Background:
In a time of unprecedented global change, the COVID-19 pandemic has led to a surge in demand of COVID-19 vaccines and related certifications. Mainly due to supply shortages, counterfeit vaccines, fake documentation, and alleged cures to illegal portfolios, have been offered on darkweb marketplaces (DWMs) with important public health consequences. We aimed to profile key DWMs and vendors by presenting some in-depth case studies.
Methods:
A non-systematic search for COVID-19 products was performed across 118 DWMs. Levels of activity, credibility, content, COVID-19 product listings, privacy protocols were among the features retrieved. Open web fora and other open web sources were also considered for further analysis of both functional and non functional DWMs. Collected data refers to the period between January 2020 and October 2021.
Results:
A total of 42 relevant listings sold by 24 vendors across eight DWMs were identified. Four of these markets were active and well-established at the time of the study with good levels of credibility. COVID-19 products were listed alongside other marketplace content. Vendors had a trusted profile, communicated in English language and accepted payments in cryptocurrencies (Monero or Bitcoin). Their geographical location included the USA, Asia and Europe. While COVID-19 related goods were mostly available for regional supply, other listings were also shipped worldwide.
Interpretation:
Findings emerging from this study rise important questions about the health safety of certain DWMs activities and encourage the development of targeted interventions to overcome such new and rapidly expanding public health threats.
Funding:
CovSaf, National Research centre on Privacy, Harm Reduction and Adversarial Influence Online (REPHRAIN), Commonwealth Fund.
Purpose of Review
Darknet-hosted drug markets (‘cryptomarkets’) are an established model of illicit drug distribution which makes use of specialised online hosting and payment systems to link buyers and sellers remotely. Cryptomarkets appear to professionalise, gentrify and integrate drug markets. Therefore, they can be hypothesised to have effects on drug availability by allowing purchases by people who use drugs (PWUD) outside of face-to-face networks that have typified drug distribution. They may attract new buyers and may change use patterns by offering a greater range of higher-potency drugs. This paper examines the research on cryptomarkets’ potential impacts on drug availability.
Recent Findings
1. Cryptomarkets tend to address established PWUD who mainly already have access to existing distribution systems. Their greatest impact may be on what is available and the quantities available, and not the overall ease of access.
2. Cryptomarkets may provide new data sources which can inform our understanding of drug markets.
3. Cryptomarkets may define PWUD as consumers and contribute to reshaping their identities around principles of self-directed, informed consumption.
4. In terms of size, cryptomarkets are currently smaller than other modes of digital drug distribution such as through social media and messaging apps and should be seen as a specialist subset of that genre.
5. Users of cryptomarkets often integrate drug-purchase and consumption repertoires across multiple sites, online and offline, and cryptomarkets can be one element.
Summary
The cryptomarkets are of interest partly because they alter the practical calculus around drug diffusion and partly because they contribute to the formation of digitally enabled drug use which emphasises a consumer relationship between buyer and seller.
Kratom is a plant that is indigenous to Southeast Asia and has recently
attracted attention in the United States; its primary active alkaloid mitragynine has stimulant effects at low doses and sedative effects at high
doses. The purpose of this study was to provide updated information on
the characteristics, clinical effects, treatment and patient outcomes of kratom exposure.
Methods: This was a retrospective analysis of kratom exposures reported
to two statewide poison control centers between January 2016 and June
2020. Subjects who reported coexposure to other substances of abuse or
intentional xenobiotic overdoses were excluded. The data were stratified
by the consumption of kratom alone and with nonoverdose exposure to
other medications.
Results: In total, 153 kratom exposures were included. Patients were classified into 3 groups according to kratom use within the past 24 hours: low
dose (1–5 g; 45.1%), moderate dose (>5–15 g; 17.0%) and high dose (>15
g; 12.4%) groups.
The two common clinical effects were central nervous system excitation
(kratom, 32.3%; coexposure, 53.3%) and tachycardia (kratom, 46.6%; coexposure, 44.6%). Dose dependent sedative effects of kratom were not
observed. Coexposure accounted for 39.2% of cases and was associated
with higher rates of ICU admission (28.3% vs. 8.6%; p<0.01) and serious
medical outcomes (28.3% vs. 7.5%; p<0.01).
Conclusion: Kratom exposure is associated with a wide range of symptoms. Despite the perception that kratom is safe, the probability of more
severe symptoms and serious effects should be o
Background
Kratom ( Mitragyna speciosa) consumption and associated health effects have raised debates in the United States. Although most people using this herb do not experience adverse health effects associated with kratom use, medical providers should be knowledgeable of emerging substances and concurrent, sequential, or simultaneous use of other drugs which may impact healthcare recommendations and prescribing practices.
Methods
The objective of this narrative review was to elucidate selected health effects associated with using kratom—either alone or with other substances. Since scientifically controlled human subjects research on kratom use is still limited, relevant case reports were also described.
Results
Cardiovascular, gastrointestinal, neurological, and psychiatric effects associated with kratom use were especially notable, and in-utero exposure accompanied concern regarding a neonate’s risk for developing neonatal abstinence syndrome. Our ability to identify and understand the role of this herb in kratom-associated fatalities is complicated since kratom is not routinely screened for in standard forensic toxicology. If a screening is performed, it is usually for the major alkaloid, mitragynine, as a surrogate for kratom use. In addition to lacking a standard practice of screening decedents for kratom alkaloids, the association between mortality and kratom use may be confounded by polysubstance use, adulteration of kratom products, and drug-herb interactions.
Conclusions
Increasing medical awareness of this herb is vital to ensuring prompt administration of best-practice medical advice or treatment for people seeking information related to kratom use or for patients experiencing an adverse health effect that may be associated with using or withdrawing from kratom. Knowledge gained from continued surveillance and study of kratom and its associated health effects may assist in guiding clinical decision-making and preventing development of adverse health effects among people using kratom.
Kratom (Mitragyna speciosa Korth., Rubiaceae) is a plant native to Southeast Asia, where it has been used for centuries as a mild stimulant and as medicine for various ailments. More recently, as kratom has gained popularity in the West, United States federal agencies have raised concerns over its safety leading to criminalization in some states and cities. Some of these safety concerns have echoed across media and broad-based health websites and, in the absence of clinical trials to test kratom’s efficacy and safety, considerable confusion has arisen among healthcare providers. There is, however, a growing literature of peer-reviewed science that can inform healthcare providers so that they are better equipped to discuss kratom use with consumers and people considering kratom use within the context of their overall health and safety, while recognizing that neither kratom nor any of its constituent substances or metabolites have been approved as safe and effective for any disease. An especially important gap in safety-related science is the use of kratom in combination with physiologically active substances and medicines. With these caveats in mind we provide a comprehensive overview of the available science on kratom that has the potential to i clarity for healthcare providers and patients. We conclude by making recommendations for best practices in working with people who use kratom.
There is limited understanding regarding kratom use among US adults. Although motivations for use are increasingly understood, typical kratom doses, threshold of (low and high) doses for perceived effectiveness, and effects produced during cessation are not well documented. We aimed to extend prior survey work by recruiting adults with current and past kratom exposure. Our goal was to better understand kratom dosing, changes in routines, and perception of effects, including time to onset, duration, and variability of beneficial and adverse outcomes from use and cessation. Among respondents who reported experiencing acute kratom effects, we also sought to determine if effects were perceived as helpful or unhelpful in meeting daily obligations. Finally, we attempted to detect any signal of a relationship between the amount of kratom consumed weekly and weeks of regular use with ratings of beneficial effects from use and ratings of adverse effects from cessation. We conducted an online survey between April-May 2021 by re-recruiting participants from a separate study who reported lifetime kratom use. A total of 129 evaluable surveys were collected. Most (59.7%) had used kratom >100 times and reported currently or having previously used kratom >4 times per week (62 weeks on average). Under half (41.9%) reported that they considered themselves to be a current “regular kratom user.” A majority (79.8%) reported experiencing acute effects from their typical kratom dose and that onset of effects began in minutes but dissipated within hours. Over a quarter reported that they had increased their kratom dose since use initiation, whereas 18.6% had decreased. Greater severity of unwanted effects from ≥1 day of kratom cessation was predicted by more weeks of regular kratom use (β = 6.74, p = 0.02). Acute kratom effects were largely reported as compatible with, and sometimes helpful in, meeting daily obligations. In the absence of human laboratory studies, survey methods must be refined to more precisely assess dose-effect relationships. These can help inform the development of controlled observational and experimental studies needed to advance the public health understanding of kratom product use.
Mitragynine, is a naturally occurring indole alkaloid that can be isolated from the leaves of a psychoactive medicinal plant. Mitragyna speciosa, also known as kratom, is found to possess promising analgesic effects on mediating the opioid receptors such as µ (MOR), δ (DOR), and κ (KOR). This alkaloid has therapeutic potential for pain management as it has limited adverse effect compared to a classical opioid, morphine. Mitragynine is frequently regarded to behave like an opioid but possesses milder withdrawal symptoms. The use of this alkaloid as the source of an analgesic candidate has been proven through comprehensive preclinical and clinical studies. The present data have shown that mitragynine is able to bind to opioid receptors, particularly MOR, to exhibit the analgesic effect. Moreover, the chemical and pharmacological aspects of mitragynine and its diastereomers, speciogynine, speciociliatine, and mitraciliatine, are discussed. It is interesting to know how the difference in stereochemical configuration could lead to the difference in the bioactivity of the respective compounds. Hence, in this review, the updated pharmacological and toxicological properties of mitragynine and its diastereomers are discussed to render a comprehensive understanding of the pharmacological properties of mitragynine and its diastereomers based on their structure–activity relationship study.
Background
The pricing of illicit drugs is typically approached within the risks and prices framework. Recent sociological and economic studies of prices in online drug markets have stressed the centrality of reputation for price formation. In this paper, we propose an account of price formation that is based on the risks and prices framework, but also incorporates internal social organization to explain price variation. We assess the model empirically, and extend the current empirical literature by including payment methods and informal ranking as influences on drug pricing.
Methods
We apply our model to estimate the prices of cannabis, cocaine, and heroin in two online drug markets, cryptomarkets (n = 92.246). Using multilevel linear regression, we assess the influence of product qualities, reputation, payment methods, and informal ranking on price formation.
Results
We observe extensive quantity discounts varying across substances and countries, and find premia and discounts associated with product qualities. We find evidence of payment method price adjustment, but contrary to expectation we observe conflicting evidence concerning reputation and status. We assess the robustness of our findings concerning reputation by comparing our model to previous approaches and alternative specifications.
Conclusion
We contribute to an emerging economic sociological approach to the study illicit markets by developing an account of price formation that incorporates cybercrime scholarship and the risks and prices framework. We find that prices in online drug markets reflect both external institutional constraint and internal social processes that reduce uncertainty.
Background: Kratom or Mitragyna speciosa (Korth.) has received overwhelming attention recently due to its alleged pain-relieving effects. Despite its potential therapeutic value, kratom use has been linked to many occurrences of multiorgan toxicity and cardiotoxicity. Accordingly, the current narrative review aimed to provide a detailed account of kratom’s adverse cardiovascular effects and cardiotoxicity risk, based on in vitro studies, poison center reports, coroner and autopsy reports, clinical case reports, and clinical studies.
Methods: An electronic search was conducted to identify all research articles published in English from 1950 to 2021 using the major research databases, such as Google Scholar, Web of Science, PubMed, Scopus, Mendeley, EMBASE, Cochrane Library, and Medline. We then analyzed the literature’s discussion of adverse cardiovascular effects, toxicity, and mortality related to kratom use.
Results: Our findings revealed that, although in vitro studies have found kratom preparations’ most abundant alkaloid—mitragynine—to cause a prolonged QTc interval and an increased risk of torsades de pointes, a clinical study examining humans’ regular consumption of kratom did not report such a risk. However, this latter study did show that regular kratom use could induce an increased QTc interval in a dose-dependent manner. A few case reports also highlighted that kratom consumption is associated with ventricular arrhythmia and cardiopulmonary arrest, but this association could have ensued when kratom was co-administered with another substance. Similarly, analyses of national poison data showed that kratom’s most common adverse acute cardiovascular effects include tachycardia and hypertension. Meanwhile, coroner and autopsy reports indicated that kratom’s cardiovascular sequelae encompass coronary atherosclerosis, myocardial infarction, hypertensive cardiovascular disease, left ventricular hypertrophy, cardiac arrhythmia, cardiomegaly, cardiomyopathy, focal band necrosis in the myocardium, and myocarditis. Given the available data, we deduced that all cardiac eventualities reported in the literature could have been compounded by polysubstance use and unresolved underlying medical illnesses.
Conclusion: Although kratom use has been associated with death and cardiotoxicity, especially at higher doses and when associated with other psychoactive drugs, the dearth of data and methodological limitations reported in existing studies do not allow a definitive conclusion, and further studies are still necessary to address this issue.
This paper investigates the functioning of Online Black-Markets (OBMs), i.e. a digital infrastructure operating in the Dark Net that enables the exchange of illegal goods such as drugs, weapons and fake digital identities. OBMs exist notwithstanding adverse conditions such as police interventions, scams and market breakdowns. Relying on a longitudinal case study, we focus on the dynamics of interactions among actors and marketplace technologies and we identify three mechanisms explaining OBMs operations. In particular, we show that OBMs infrastructure is the result of commoditization, platformization and resilience processes. Our contribution relies on the identification of community-based mechanisms that generate the OBMs infrastructure, extending the current understanding of e-commerce and social commerce.
Kratom (Mitragyna speciosa, Korth.) is an evergreen tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations, native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Despite the long history of kratom use in Asia, it is only within the past 10–20 years that kratom has emerged as an important herbal agent in the United States, where it is being used for the self-treatment of pain, opioid withdrawal symptoms, and mood disorders. The increase in the use of kratom in the United States has coincided with the serious epidemic of opioid abuse and dependence. Since 2015, efforts to restrict access to prescription opioids have resulted in a marked increase in the use of “street” opioids such as heroin and illicit fentanyl. At the same time, many patients with chronic pain conditions or opioid use disorder have been denied access to appropriate medical help. The lack of access to care for patients with chronic pain and opioid use disorder has been magnified by the emergence of the COVID-19 pandemic. In this report, we highlight how these converging factors have led to a surge in interest in kratom as a potential harm reduction agent in the treatment of pain and opioid use disorder.
Introduction
Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption.
Objective
Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans.
Methods
A systematic literature search using PubMed and the Medline database was conducted between April and November 2020.
Results
Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal).
Conclusions
Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.
Recently, online black markets and anonymous virtual currencies have become the subject of academic research, and we have gained a certain degree of knowledge about the dark web. However, as terms such as deep web and dark net, which have different meanings, have been used in similar contexts, discussions related to the dark web tend to be confusing. Therefore, in this paper, we discuss the differences between these concepts in an easy-to-understand manner, including their historical circumstances, and explain the technology known as onion routing used on the dark web.
Background: Kratom has a long history of traditional medicine use in Southeast Asia. Consumption of kratom products has also been reported in the US and other regions of the world. Pain relief is among many self-reported kratom effects but have not been evaluated in controlled human subject research. Methods: Kratom effects on pain tolerance were assessed in a randomized, placebo-controlled, double-blind study. During a 1-day inpatient stay, participants received a randomized sequence of kratom and placebo decoctions matched for taste and appearance. Pain tolerance was measured objectively in a cold pressor task (CPT) as time (seconds) between the pain onset and the hand withdrawal from the ice bath. Health status, vital signs, objective, and subjective indicators of withdrawal symptoms, self-reported data on lifetime kratom use patterns, and assessments of blinding procedures were also evaluated. Results: Twenty-six males with the mean (SD) age 24.3 (3.4) years were enrolled. They reported the mean (SD) 6.1 (3.2) years of daily kratom consumption. Pain tolerance increased significantly 1 hour after kratom ingestion from the mean (SD) 11.2 (6.7) seconds immediately before to 24.9 (39.4) seconds 1 hour after kratom consumption (F(2,53.7)=4.33, p=0.02). Pain tolerance was unchanged after consuming placebo drinks: 15.0 (19.0) seconds immediately before and 12.0 (8.1) seconds 1 hour after consumption of placebo (F(2,52.8)=0.93, p=0.40). No discomfort or signs of withdrawal were reported or observed during 10-20 hours of kratom discontinuation. Conclusions: Kratom decoction demonstrated a substantial and statistically significant increase in pain tolerance. Further rigorous research on kratom pain-relieving properties and a safety profile is needed.
Background
The United States is facing a "triple wave" epidemic fueled by novel synthetic opioids. Cryptomarkets, anonymous marketplaces located on the deep web, play an increasingly important role in the distribution of illicit substances. This article presents the data collected and processed by the eDarkTrends platform concerning the availability trends of novel synthetic opioids listed on one cryptomarket.
Methods
Listings from the DreamMarket cryptomarket "Opioids" and "Research Chemicals" sections were collected between March 2018 and January 2019. Collected data were processed using eDarkTrends Named Entity Recognition algorithm to identify opioid drugs, and to analyze their availability trends in terms of frequency of listings, available average weights, average prices, and geographic indicators of shipment origin and destination information.
Results
95,011 opioid-related listings were collected through 26 crawling sessions. 33 novel synthetic opioids were identified in 3.3% of the collected listings. 44.7% of these listings advertised fentanyl (pharmaceutical and non-pharmaceutical) or fentanyl analogs for an average of 2.8 kgs per crawl. "Synthetic heroin" accounted for 33.2% of novel synthetic opioid listings for an average 1.1 kgs per crawl with 97.7% of listings advertised as shipped from Canada. Other novel synthetic opioids (e.g., U-47,700, AP-237) represented 22% of these listings for an average of 6.1 kgs per crawl with 97.2% of listings advertised as shipped from China.
Conclusions
Our data indicate consistent availability of a wide variety of novel synthetic opioids both in retail and wholesale-level amounts. Identification of new substances highlights the value of cryptomarket data for early warning systems of emerging substance use trends.
Kratom or Mitragna speciosa is a tropical tree that is indigenous to Southeast Asia, where it has been used for various medicinal reasons. In the West, it is used in the self-treatment of opioid withdrawal, pain, and a variety of mood and anxiety states. Two active ingredients in kratom are mitragynine and 7-hydroxymitragynine, which have affinity at the mu-opioid receptor among others. Kratom is easily available over the Internet and its use is increasing in the United States. It is currently listed by the Drug Enforcement Administration as a drug of concern. In 2017, the U.S. Food and Drug Administration started issuing a series of warnings about kratom, and by early 2018, it released a statement identifying 44 deaths related to kratom use. The Centers for Disease Control and Prevention has also reported 91 deaths directly linked to kratom use in 2019. Although its safety profile needs additional research for clarification, there have been reports of kratom-induced or kratom-related respiratory depression, hypothyroidism, secondary hypogonadism, hyperprolactinemia, psychosis, and seizures. We report a case of kratom-induced tonic-clonic seizures in a 27-year-old Caucasian male with a psychiatric history of anxiety, attention-deficit/hyperactivity disorder, benzodiazepine use disorder, and opioid use disorder. He was hospitalized after a witnessed tonic-clonic seizure. There was no significant metabolic abnormality on laboratory testing. Spinal cord and brain imaging were unremarkable, whereas his urine toxicology was positive for opioids only, which was likely a false-positive result due to cross-reactivity with his sleeping aids. He was evaluated by the Consultation-Liaison Psychiatry team for psychotic symptoms. On evaluation, the patient's psychosis had resolved, but he endorsed racing thoughts, significant anxiety, and insomnia. He admitted to drinking three to four 8-mL bottles of Kratom daily for one-and-a-half years to self-medicate his anxiety after losing his health insurance. In the hospital, he was treated with anxiolytics, counseled to abstain from Kratom use, and was referred for substance use disorder treatment. This case highlights the life-threatening complications of Kratom that is easily available online.
Purpose of Review
This review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal.
Recent Findings
Multiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events.
Summary
Reports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.
Kratom (Mitragyna speciosa) is a tree-like 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. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological 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 I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mi-tragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mi-tragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.
Context: Kratom, or Mitragyna speciosa, is a plant indigenous to Southeast Asia that has gained national attention in the United States for its increased use in the self-management of opioid withdrawal and pain, as well as for concerns about its safety.
Methods: This study analyzes exposures to kratom reported to poison control centers (PCCs) in the United States during 2011–2017 from the National Poison Data System (NPDS).
Discussion: From 2011 through 2017, 1807 kratom exposures were reported to United States PCCs. Almost two-thirds (65.0%) of these exposures occurred during 2016–2017. Most exposures occurred among adults ≥20 years (88.9%), males (70.8%), at a residence (86.1%), and were intentional (74.3%). Among first-ranked kratom exposures, 31.8% resulted in admission to a health care facility (HCF) and 51.9% in a serious medical outcome. Multiple-substance exposures were associated with greater odds of admission to a HCF (OR: 2.80; 95% CI: 2.21–3.55) and a serious medical outcome (OR: 2.25; 95% CI: 1.77–2.85) compared with single-substance exposures. There were 11 deaths associated with kratom exposure, including two that occurred after exposure to kratom only. Among kratom-only exposures, 86.1% resulted in one or more clinical effects. The most common clinical effects were agitation/irritability (22.9%) and tachycardia (21.4%). There were seven neonatal exposures, including five experiencing withdrawal.
Conclusions: Kratom is associated with a variety of serious medical outcomes, especially when used with other substances. More research is needed to define the human response to kratom. Increased regulation of kratom products would help guarantee product quality and safety. Individuals who choose to use kratom should be educated about its potential risks, including the dangers of using it in combination with other substances.
This case report describes an overdose on kratom, and elicits the potential dangers of overdose on the regulated dietary supplement. A young male presented to the emergency department intubated after being found unresponsive. He was found by his family to be unarousable and agonal breathing with minimal response to naloxone administered by Emergency Medical Services (EMS). Urine toxicology and blood alcohol content were negative. Physical exam was significant for tachycardia, hypotension, and pinpoint pupils with sluggish reactivity to light. Laboratory studies were significant for elevated liver enzymes, blood urea nitrogen, creatinine, lipase, amylase, troponins, and lactic acid. Family members revealed that the patient consumed kratom, which he obtained through an e-commerce business, and had consumed over 500 grams the previous day. Urine sample for kratom on day 3 tested positive with levels of more than 500 ng/dL. The patient received supportive care and, by day 10, pupillary reflexes returned to normal and he was extubated by day 14. Most of the medications/drugs labelled under herbal supplements by the U.S. Food and Drug Administration (FDA) are not regulated and can be purchased over the counter. The safety and side-effect profile of kratom is not well-studied, especially in an overdose scenario.
Recent years have seen a widespread increase in kratom use, not just for the purpose of easing opioid withdrawal, but also for management of emotional and mental health concerns by individuals without histories of opioid use. Chronic use can lead to dependence, tolerance, and withdrawal on cessation, and clinicians are seeing an increasing number of presentations involving the latter. Although there is literature discussing the use of kratom to assist in opioid withdrawal, this article comprehensively examines independent withdrawal from kratom. We systematically review existing evidence and provide our own clinical cases. Clinicians need to be aware of the withdrawal symptomatology and implement a similar approach as for opioid withdrawal with long-term maintenance to prevent relapse. ARTICLE HISTORY
Kratom is a plant with dose-dependent mixed stimulant and opioid properties whose pharmacologic characteristics and social impact continue to be described. The main active isolate of kratom is mitragynine, an indole-containing alkaloid with opioid-like effects. Kratom toxicity and kratom-associated fatalities have been described, including those in association with additional drugs. In this paper we describe the case of a 27-year-old man who was found deceased with a toxic blood concentration of quetiapine in conjunction with the qualitative presence of mitragynine. Investigative and autopsy findings suggested perimortem hyperthermia and seizure-like activity. Kratom toxicity and kratom-associated fatalities are being increasingly reported. Experiments with kratom extracts have shown inhibitory effects upon hepatic CYP enzymes, leading to previous speculation of the potential for clinically significant interactions between kratom and a wide array of medications. Herein is described a fatal case of quetiapine toxicity complicated by mitragynine use. The potential ability of mitragynine to alter the pharmacokinetics of a prescription medication via inhibition of its hepatic metabolism is discussed.
Background. Kratom is a drug derived from the leaves of the tree Mitragyna speciose, which is native to southern Thailand. The route of administration is oral. Kratom has become increasingly available in the United States. The active ingredients in the drug bind the opioid mu-receptor; therefore, kratom has similar physiological effects as mu-opioids. Elevated prolactin is a common medical condition frequently caused by a variety drugs, including opioids. Case Report. A 42-year-old man presented with poor energy and low libido. He had mildly elevated serum prolactin with hypogonadotropic hypogonadism as evidenced by low serum testosterone with luteinizing hormone and follicle-stimulating hormone in the normal range. At his initial visit, he reported no use of any recreational or therapeutic drug. Two months later when seen in follow-up, both the testosterone and prolactin levels had returned to normal. At that visit he reported frequent use of kratom, which he had discontinued a few days after the first visit. Discussion. Kratom is now widely available in health food stores and online and is considered an emerging drug of abuse. At present kratom is legal in the United States, but recently the Drug Enforcement Administration served noticed of its intention of making kratom a Schedule I drug. A number of adverse events or side effects have been reported, but this is the first report of hyperprolactinemia as the result of ingestion of kratom.
The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets and considers whether crypto markets are a reliable platform for the sale of NPS. Data was collected from 22 crypto markets that were accessed through the hidden web using the Onion Router (Tor). Data collection took place bimonthly from October 2015 to October 2016 as part of the CASSANDRA (Computer Assisted Solutions for Studying the Availability aNd DistRibution of novel psychoActive substances) project. In seven snapshots over 12 months, 808 unique vendors were found selling 256 unique NPS. The total number of individual NPS and vendors increased across the data collection period (increase of 93.6% and 71.6%, respectively). Only 24% (n = 61) of the total number of NPS and 4% (n = 31) of vendors appeared in every snapshot over the 12 months, whereas 21% (n = 54) of NPS and 45% (n = 365) of vendors only appeared once throughout the data collection. The individual NPS and vendors did not remain the same over the 12 months. However, the availability of NPS and vendors selling NPS grew. NPS consistently available on crypto markets could indicate popular substances.
From 2018 to 2021, seizures of counterfeit oxycodone pills containing non-pharmaceutical fentanyl or other novel synthetic opioids increased significantly contributing to continuing increases in overdose mortality in Northern America. Evidence suggests that counterfeit pills are distributed through cryptomarkets. This article presents data regarding the availability and characteristics of oxycodone pills advertised on one major cryptomarket between January and March 2022. Collected data were processed using a dedicated Named Entity Recognition algorithm to identify oxycodone listings and categorized them as either counterfeit or pharmaceutical. Frequency of listings, average number of pills advertised, average prices per milligram, number of sales, and geographic indicators of shipment origin and destination were analyzed. In total, 2,665 listings were identified as oxycodone. 48.2% (1,285/2,665) of these listings were categorized as counterfeit oxycodone, advertising a total of 652,699 pills (93,242.7 pills per datapoint) offered at a lower price than pharmaceutical pills. Our data indicate the presence of a large volume of counterfeit oxycodone pills both in retail- and wholesale-level amounts mostly targeting US and Canadian customers. These exploratory findings call for more research to develop epidemiological surveillance systems to track counterfeit pill and other drug availability on the Dark web environment.
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.
Mitragyna speciosa, a species of plant that is native to Thailand, Malaysia and Southeast Asia, contains two major psychoactive alkaloids: mitragynine and 7-hydroxymitragynine. Pharmacologically, the alkaloids exhibit biphasic effects - at low dose, stimulant effects are realized, while high doses exhibit sedative effects. For years, the plant has been used recreationally and medicinally for these effects, but its use has been implicated in and associated with intoxications and deaths. In this case report we describe two cases whereby decedents presented with single substance fatal intoxications by mitragynine in the absence of other postmortem toxicological findings. The cases entail young male decedents in outdoor settings (e.g. driving a vehicle and bicycle). Postmortem blood concentrations were 2,325 ng/mL and 3,809 ng/mL. The medical examiner (ME) certified cause of death (COD) as acute mitragynine intoxication in both cases. The toxicology results presented become useful when considering mitragynine to be the offending agent in lethal single drug intoxications; further, the information included is pertinent to medical examiners, forensic pathologists, forensic toxicologists, and emergency department personnel in evaluating possible poisoning and lethality by mitragynine.
Introduction:
Since 2007, kratom use in the United States has increased, centered around nonmedical self-treatment of pain, psychiatric, and substance use disorder symptoms. Reports of kratom withdrawal have emerged amidst description of therapeutic effects, yet we know little about disordered use. Our objective was to assess Diagnostic and Statistical Manual-5 substance use disorder for kratom ("kratom use disorder," KUD) and examine kratom withdrawal symptoms among those who ever used regularly. We also sought to identify clinical characteristics of respondents who qualified for current, remitted, or never KUD.
Methods:
Between April and May 2021, we re-recruited online respondents who reported lifetime kratom use on an unrelated survey into our cross-sectional kratom survey study, permitting a diverse sample of current and former kratom-using persons.
Results:
A total of 129/289 (44.6%) evaluable surveys were obtained. Over half (52.7%) of respondents never met KUD diagnostic criteria; 17.8% were assessed remitted, and 29.5% met current (past-year) KUD threshold. For past-year KUD, severity was: 14.0% mild, 7.0% moderate, and 8.5% severe. Pain, psychiatric symptoms, and polydrug use were found across all groups. KUD symptoms reflected increased use, tolerance, withdrawal, unsuccessful quit attempts, and craving; 9.3% reported decreases in important social, occupational, or recreational activities because of use. Withdrawal symptoms were moderate and included gastrointestinal upset, restlessness, anxiety, irritability, fatigue/low energy, and craving.
Conclusions:
As assessed here, tolerance and withdrawal are primary KUD features rather than psychosocial impairments. As kratom is often used among persons with a myriad of health conditions, clinicians should be aware of and assess for kratom use and withdrawal.
Background
Digital technologies continue to facilitate drug trading. Televend was an innovative combination of multiple digital technologies, with its backend hosted on the darknet, while purchases were made through the messaging app Telegram. Here, we provide an initial characterisation of this nascent market.
Methods
Televend and White House Market (WHM) were scraped (Jun–Jul 2021) and a global cross-sectional web survey of 15,513 drug buyers (Global Drug Survey; GDS) was conducted (Dec 2020–Mar 2021).
Results
Televend was 10% of the size of WHM, the largest drug cryptomarket (4,515/44,830 listings per week). Both markets predominantly contained drug-related listings covering similar drug categories, with similar country of origin and destination. Very few GDS drug buyers reported use of Televend (0.73%). Most Televend buyers (68/114) reported buying cannabis, then cocaine (20), MDMA (17), and LSD (12). The Televend and darknet groups had similar demographic and drug use characteristics; whereas compared with app purchasers, older age increased the odds of Televend use (aRRR=1.06, p<.001), identifying as a cisgender woman decreased the odds (aRRR=0.43, p=.004), while last-year use of a greater number of drug types (aRRR=1.20, p<.001) and less frequent drug use (aRRR=0.998, p=.032) increased the odds of Televend purchase.
Conclusions
While smaller, Televend was not noticeably different in its drug offerings to its largest cryptomarket competitor, and it attracted a cohort more similar to darknet than to app drug buyers. Future Televend-like markets may be attractive to people with less specialised technical knowledge who already routinely scroll through social media feeds.
Kratom (Mitragyna speciosa) consists of over 40 alkaloids with two of them, mitragynine (MG) and 7‐OH‐mitragynine (7‐OH‐MG) being the main psychoactive compounds. MG and 7‐OH‐MG each target opioid receptors and have been referred to as atypical opioids. They exert their pharmacologic effects on the μ, δ, and κ opioid receptors. In addition, they affect adrenergic, serotonergic, and dopaminergic pathways. Kratom has been touted as an inexpensive, legal alternative to standard opioid replacement therapy such as methadone and buprenorphine. Other uses for kratom include chronic pain, attaining a “legal high,” and numerous CNS disorders including anxiety depression and post‐traumatic stress disorder (PTSD). Kratom induces analgesia and mild euphoria with a lower risk of respiratory depression or adverse central nervous system effects compared to traditional opioid medications. Nonetheless, kratom has been associated with both physical and psychological dependence with some individuals experiencing classic opioid withdrawal symptoms upon abrupt cessation. Kratom use has been linked to serious adverse effects including liver toxicity, seizures, and death. These risks are often compounded by poly‐substance abuse. Further, kratom may potentiate the toxicity of coadministered medications through modulation of cytochrome P450, P‐glycoprotein, and uridine diphosphate glucuronosyltransferase enzymes (UGDT). In 2016 the U.S. Drug Enforcement Administration (DEA) took steps to classify kratom as a federal schedule 1 medication; however, due to public resistance, this plan was set aside. Until studies are conducted that define kratom's role in treating opioid withdrawal and/or other CNS conditions, kratom will likely remain available as a dietary supplement for the foreseeable future. This article is protected by copyright. All rights reserved
Background
Novel synthetic opioids are fueling the overdose deaths epidemic in North America.Recently, non-fentanyl novel synthetic opioids have emerged in forensic toxicological results. Cryptomarkets have become important platforms of distribution for illicit substances. This article presents the data concerning the availability trends of novel non-fentanyl synthetic opioids listed on one cryptomarket.
Methods
Listings from the EmpireMarket cryptomarket "Opiates" section were collected between June 2020 and August 2020. Collected data were processed using eDarkTrends Named Entity Recognition algorithm to identify novel synthetic opioids, and to analyze their availability trends in terms of frequency of listings, available average weights, average prices, quantity sold, and geographic indicators of shipment origin and destination information.
Results
35,196 opioid-related listings were collected through 12 crawling sessions. 17 nonfentanyl novel synthetic opioids were identified in 2.9 % of the collected listings for an average of 9.2 kg of substance available at each data point. 587 items advertised as non-fentanyl novel synthetic opioids were sold on EmpireMarket for a total weight of between 858 g and 2.7 kg during the study period. 45.5% of these listings were advertised as shipped from China.
Conclusions
Fourteen of the 17 non-fentanyl novel synthetic opioids were identified for the first time on one large cryptomarket suggesting a shift in terms of novel non-fentanyl synthetic opioids availability. This increased heterogeneity of available novel synthetic opioids could reduce the efficiency of existing overdose prevention strategies. Identification of new opioids underpins the value of cryptomarket data for early warning systems of emerging substance use trends.
Objectives:
Kratom (Mitragyna speciosa Korth.), an indigenous medicinal plant, has been widely used as a traditional remedy in Southeast Asia. However, its combined consumption with other substances has received scarce attention. This study investigates the use of kratom among adults with a history of using heroin and methamphetamine in Malaysia.
Methods:
A total of 332 patients who were mandated to undergo drug rehabilitation participated in this cross-sectional study. The study data were collected through face-to-face interviews using a semi-structured questionnaire.
Results:
The majority were males (95%, n = 314/332) and Malays (98%, n = 325/332) with a mean age of 32.3 years (SD = 9.16). Over two thirds of the respondents used kratom to alleviate heroin withdrawal symptoms and to reduce methamphetamine intake; 59% used it as a substitute for heroin and methamphetamine. A similar proportion used kratom to reduce heroin intake (58%), while only 15% used it for its euphoric effects. Multivariate analysis showed that previous attendees of government rehabilitation programs had lower odds of using kratom as a heroin substitute.
Conclusions:
The potential of kratom to alleviate heroin withdrawal symptoms, and to reduce methamphetamine and heroin intake, among people who co-use heroin and methamphetamine warrants further research.
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.
Kratom is an unregulated kappa-opioid receptor agonist available for order on the internet that is used as a remedy for chronic pain. We present a case of a middle-aged man who suffered a cardiac arrest in the setting of kratom ingestion.
Background
The absence of an FDA-approved medication for the treatment of cocaine use disorder (CUD) may, in part, reflect the varying conditions present when the decision to use cocaine is made, with one medication unlikely to work under all conditions. The objective of this double-blind, placebo-controlled, human laboratory study was to test the effects of modafinil, a medication with mixed efficacy for the treatment of CUD, using a novel self-administration procedure designed to model distinct clinical scenarios.
Methods
During modafinil maintenance (0, 300 mg/day), participants chose to self-administer up to 7 doses of smoked cocaine (25 mg) under 9 conditions: immediately after exposure to: (a) cues associated with cocaine and a non-contingent cocaine administration, i.e. 'prime' (25 mg), (b) only cocaine cues, and (c) neither cues nor cocaine. Each condition was tested when self-administered cocaine cost 5, 10 and 388 ± 218/week on cocaine and with no history of alcohol use disorder, completed the study. Relative to placebo, modafinil robustly attenuated self-administration when cocaine was expensive (10,15/dose) and when there was no 'prime.' Modafinil had no effect on self-administration when cocaine was inexpensive ($5/dose) or when participants received a 'prime.'
Conclusions
Modafinil's effects on cocaine-taking varied substantially as a function of recent cocaine exposure and cost, which may help explain the mixed clinical findings. Modafinil may be most effective for preventing relapse in abstinent patients, particularly under conditions in which cocaine is costly, rather than initiating abstinence for those continuing to use cocaine.
Background
In an age of global insecurity, highly potent synthetic drugs have become a major public health issue. Their online advertisement and sale are facilitated by surface web, darknet markets and social media fuelling substance abuse and addiction, as well as various types of new criminal activities and their growth in sophistication. This study presents a systematic analysis of the darknet sale of one of the most potent synthetic opioids: Carfentanil. With an equianalgesic potency of 10.000 times a unit of morphine, its toxicity is comparable to traditional nerve agents, and it has been previously used as a chemical weapon, causing human fatalities.
Methods
Digital trace data was collected retrospectively from all the darknet marketplaces, which have been active in the past five years. Data on vendors offering Carfentanil on Agartha, Empire and Yakuza marketplaces were analysed with regard to items sold and sellers’ features as these were the only active markets at the time of search. Searches were carried out in the English language only.
Results
63 Cartfentanil vendors operating on 19 darknet marketplaces were identified. Contacts and payments were facilitated with end-to-end encryption messaging mobile applications and content-expiring messages. Although it is known that Agartha is a scam market, and no operative sellers were found on Yakuza, several sellers promoting Carfentanil sales were active in the Empire marketplace with a number of transaction ranging from 4 to 1223.
Conclusion
The availability of highly potent drugs such as Carfentanil on the darknet requires the urgent development of novel scientific methods and tools able to monitor and to predict such new threats, while informing policymaking and protecting the health and the security of citizens.
Background: Interest in the Southeast Asian natural remedy kratom has increased in Western countries recently, along with increasing concern over its potential toxic effects.
Objective: To describe and compare demographics, common co-exposure substances, clinical effects, treatments, and medical outcomes of kratom “abuse” exposures in the United States (US) and Thailand.
Methods: This is a retrospective analysis of kratom “abuse” exposures, defined as use when attempting to gain a psychotropic effect, reported to the National Poison Data System (NPDS) in the US and the Ramathibodi Poison Center (RPC) in Thailand from 2010 to 2017. Multivariate analysis identified risk factors for severe medical outcomes, defined as both ICU admissions and death.
Results: Nine-hundred-twenty-eight cases were included (760 from NPDS and 168 from RPC). A greater proportion of cases involved co-exposures in Thailand (64.8% versus 37.4%; odds ratio [OR] = 3.10, 95% confidence interval [CI] = 2.15–4.47, p < .01). Both countries had a similar prevalence of opioid and benzodiazepine co-ingestions, but the US had more co-ingestions with other sedatives (4.6% versus 0%, OR = 0, 95% CI = 0–0.47, p < .01). Common clinical effects included tachycardia (30.4%), agitation/irritability (26.2%), and drowsiness/lethargy (21.1%). Six deaths occurred, including one single-substance exposure in the US, three multiple-substance exposures in the US, and two multiple-substance exposures in Thailand. IV fluid administration was provided more frequently in the US (OR = 18.82, 95% CI = 5.85–60.56, p < .01).
Conclusions: Despite lower frequencies of co-ingestants overall, US kratom abuse exposures yielded greater clinical severity. This disparity may be attributable to differences in the products labeled “kratom,” greater sedative co-exposures in the US, and/or differences in population genetics or use patterns.
Kratom, or Mitragyna speciosa Korth., is a tropical plant prevalent in Southeast Asia, and it is utilized as a traditional remedy for symptomatic relief of various illnesses. It has been labeled as an atypical opioid with significant narcoticlike properties, capable of inducing kratom dependence among those who misuse or abuse it. The prevalence of kratom use has drastically increased worldwide, raising concerns among healthcare providers, particularly regarding the availability of efficacious treatment options for kratom dependence. This manuscript provides a comprehensive narrative review of literature focusing on the psychoactive alkaloids of kratom, the possible neurobiological and pathophysiological models underlying the occurrence of kratom dependence, and the clinical presentations and effective treatment options available for kratom dependence. The psychoactive alkaloids of kratom, such as mitragynine (MG) and 7-hydroxymitragynine (7-HMG), act as partial mu opioid agonists and induce kratom dependence. As a result, regular kratom use leads to withdrawal symptoms on abstinence, along with craving, tolerance, and cross-tolerance to morphine. The psychological withdrawal symptoms reported include depressed mood, anxiety, restlessness, irritability, and feeling tense, while the physical withdrawal symptoms are myalgia and body ache, joint pain, lacrimation, running nose, yawning, insomnia, diarrhea, feverish sensation, loss of appetite, tremors, itching over the body, loss of concentration, and chills. Neonatal withdrawal symptoms, such as oral intolerance, restlessness, irritability, and vomiting, are also reported in newborns of women who are on regular kratom use. Sublingual buprenorphine-naloxone (Suboxone) is reported as a promising treatment for detoxification and maintenance replacement therapy for kratom-dependent users. Alternative treatments for in-patient detoxification include intravenous clonidine and a combination of oral dihydrocodeine and lofexidine. We conclude by adding a note on the research gap concerning kratom dependence, which future studies should focus on.
Background
Amidst the opioid crisis, many people are turning to plant-based kratom for self-treatment of pain, opioid addiction, and for recreational use. Its legality is variable and its safety and medicinal effects are not agreed upon. It is broadly available from Internet Kratom Vendors (IKVs).
Methods
An examination of the online marketplace for kratom was conducted to provide context to the market amidst regulatory attempts by the Food and Drug Administration (FDA) and state legislatures. A complex search strategy identified 663 English-language IKVs selling kratom for home delivery. The 100 most popular were selected for in-depth content analysis. IKVs were visited once for content analysis data collection in December, 2017 and revisited in April 2018 to assess responses to FDA action. IKV website and social media profiles were coded for topics including location, payment and shipping options, age verification, health warnings and disclaimers, and grassroots advocacy regarding upcoming state/federal regulations.
Results
Forty-seven percent of IKVs claimed that kratom provides pain relief, 25% claimed it provides relief from opioid withdrawal, 81% featured a disclaimer that kratom is addictive, 54% stated that kratom is not FDA approved, and 66% featured disclaimers that it was not intended for consumption. Only 5% of vendors advertised effective age verification (such as verifying age at delivery). Compliance on the vendor's part with state and local bans varied by ban location, with only 27% prohibiting sales to Rhode Island while 65% did not ship to Indiana.
Conclusions
IKVs provide easy access to a wide variety of unregulated intoxicating products with poor age verification and low adherence to US state- and local-level restrictions. There is a high prevalence of vendors featuring health claims forbidden by the Food and Drug Administration. Lessons learned from regulating the Internet cigarette sales industry could be effectively applied to IKVs with future efforts.
Kratom (Mitragyna speciosa) leaves contain the mu opioid Kupferschmidt,partial agonists mitragynine and 7-hydroxymitragynine. The US Drug Enforcement Agency considers it a ‘drug of concern’, and the US FDA is reviewing kratom, but there is a paucity of information regarding health effects. Liver injury is often cited as a potential health consequence, however the same few case reports are repeatedly referenced, without a broader context. Furthermore, reports have largely lacked standardized causality assessment methods. The objective is to evaluate causality in kratom liver injury, through a comprehensive scoping review of human cases, and by reviewing epidemiologic, animal, and mechanistic reports that relate to kratom liver injury. Hepatotoxicity causality was systematically examined using the Roussel Uclaf Causality Assessment Method (RUCAM) for case reports. Biopsy findings, potential pathophysiologic mechanisms, and management options are discussed. This review identified 26 case reports and abstracts, in addition to 7 cases reported from the Drug-Induced Liver Injury Network, 25 in FDA databases, and 27 in internet user forums. Latency periods to symptom onset had a median of 20.6 days and mean of 21 days (range 2–49). Common presenting signs and symptoms were abdominal discomfort, jaundice, pruritis, and dark urine. Histologic findings were predominantly cholestatic, although, biochemically, the condition was heterogenous or mixed; the median R ratio was 3.4 and the mean was 4.6 (range 0.24–10.4). Kratom likely causes liver injury based on the totality of low-quality human evidence, and, in the context of epidemiologic, animal, and mechanistic studies. It remains unclear which subgroups of users are at heightened risk.
Introduction
Kratom is derived from the plant Mitragyna speciosa which is indigenous to Southeast Asia. Active compounds, mitragynine and 7-hydroxymitragynine, cause mild stimulant and opioid agonist effects. Although reported to have potential benefits in the treatment of opioid use disorder, efficacy remains uncertain while adverse health effects have been reported. A compounding concern is the presence of adulterants given that this is an unregulated product.
Case Details
A 54-year-old fitness instructor who used an online purchased kratom product regularly for one year developed stimulatory effects and suffered a large hemorrhagic stroke with a close temporal relationship to ingestion of a different kratom product from the one he regularly used. A collaborative investigation by medical toxicologists, a regional poison center, the state public health laboratory, and public health officials determined that his new kratom product was adulterated with phenylethylamine (PEA).
Discussion
We report a case of PEA adulterated kratom purchased and used with resultant adverse effects. PEA is structurally similar to amphetamine and is known to produce sympathomimetic effects. It is possible the stimulatory effect of PEA resulted in a marked and transient increase in blood pressure resulting in hemorrhagic stroke.
Conclusion
Medical toxicologists should form working relationships with laboratories and public health officials to aid in early identification of adulterated products that carry risk to the general population.
Objectives:
To determine whether diagnosed pre-existing health conditions correlate with Kratom demographics and use patterns.
Methods:
A cross-sectional, anonymous US national online survey was conducted among 8049 Kratom users in October, 2016 to obtain demographic, health, and Kratom use pattern information.
Results:
People who use Kratom to mitigate illicit drug dependence self-reported less pain and better overall health than individuals who used Kratom for acute/chronic pain. Self-reported improvements in pre-existing mental health symptoms (attention deficit and hyperactivity disorder/attention deficit disorder, anxiety, bipolar disorder, post-traumatic stress disorder, and depression) attributed to Kratom use were greater than those related to somatic symptoms (back pain, rheumatoid arthritis, acute pain, chronic pain, fibromyalgia). Demographic variables, including female sex, older age, employment status, and insurance coverage correlated with increased likelihood of Kratom use.
Conclusions:
Kratom use may serve as a self-treatment strategy for a diverse population of patients with pre-existing health diagnoses. Healthcare providers need to be engaging with patients to address safety concerns and potential limitations of its use in clinical practice for specific health conditions.
Background
Kratom ( Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events.
Aims
This study details the characteristics of such fatalities and provides a ‘state-of-the-art’ review.
Methods
UK cases were identified from mortality registers by searching with the terms ‘kratom’, ‘mitragynine’, etc. Databases and online media were searched using these terms and ‘death’, ‘fatal*’, ‘overdose’, ‘poisoning’, etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis.
Results
Typical case characteristics ( n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues.
Conclusions
These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom’s safety profile remains only partially understood; toxic and fatal levels require quantification.
Background:
Kratom is a South Eastern Asian tree whose leaves are used to make tea-like brews or swallowed in powdered form for various health and well-being reasons including to relieve pain and opioid withdrawal. It is important to learn more about the potential public health impact of kratom in the context of the opioid epidemic.
Methods:
An anonymous online survey of kratom users (2867 current users and 157 former users) was conducted in September 2017 through the American Kratom Association and associated social media sites.
Results:
Kratom was used primarily to relieve pain (endorsed by 48% of respondents), for anxiety, PTSD, or depression (22%), to increase energy or focus (10%) and to help cut down on opioid use and/or relieve withdrawal (10%). Over 90% of respondents who used it in place of opioids indicated that it was helpful to relieve pain, reduce opioid use, and relieve withdrawal. The reported incidence of bad adverse reactions was 13%, and reactions were overwhelmingly mild and self-managed.
Conclusions:
Respondents reported using kratom for conditions which often require use of opioids, including pain and reduction of opioid use. The high self-reported efficacy and low incidence of adverse reactions associated with kratom use suggest that it may provide a potential alternative to opioids for some persons even though it has not been evaluated in multi-center clinical trials or approved for any therapeutic purpose. Further study of kratom, including systematic characterization of its safety and efficacy for various conditions is warranted.
Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self‐treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, a UPLC‐MS/MS method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7‐hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10 mM, pH 3.5). The developed method was linear over a concentration range of 1‐200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 min. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid‐rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7‐38.7 %w/w), paynantheine (0.3‐12.8 %w/w), speciociliatine (0.4‐12.3 %w/w), and speciogynine (0.1‐5.3 %w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7‐hydroxymitragynine, isocorynantheidine) were also quantified (0.01‐2.8 %w/w) in the analyzed products, however mitraphylline was below the lower limit of quantification in all analyses.
Mitragynine is amongst the more than 40 natural indole alkaloids derived from the Mitragyna speciosa, or kratom tree, also referred to as ketum. The compound is unique in that it exhibits dose-dependent clinical outcomes with stimulant effects at lower doses but sedative effects at higher concentrations. It is indigenous to Southeast Asia, where the local population has had extensive experiences utilizing the substance for its medicinal as well as recreational effects. Mitragynine is advertised as an herbal remedy and is readily accessible via the Internet, resulting in its expansive distribution throughout the world. The addictive potential of this substance is quickly becoming recognized and mitragynine has been implicated in multidrug toxicity deaths. We present a case of the first reported mitragynine-associated fatality in Canada where an independently fatal mitragynine concentration was detected in the postmortem femoral venous blood and the source drug was likely obtained as a powder from Indonesia. Acad Forensic Pathol. 2018 8(2): 340-346