Background: Kratom's rise in popularity during multiple overlapping drug use crises is potentially driving poor mental health outcomes and straining health systems.Objective: To investigate temporal changes in the compounding effect of kratom on serious mental illness (SMI) when co-used with other drugs.Methods: We used the National Survey of Drug Use and Health (2021-2023; N = 139,524; male n = 61,926; female n = 77,598) to identify SMI, a range of drug use disorders (SUD), and kratom use. Our focal predictor was whether an individual had 1) no SUD and no kratom use, 2) an SUD without kratom, 3) kratom use without an SUD, or 4) both an SUD and kratom use. We used multiple logistic regression to model whether SMI is associated with SUD/kratom status, year, and their interactions.Results: Roughly 6% of adults met the criteria for SMI. We found that the increase in SMI over 3 years was fastest and markedly different among those with both OUD and kratom use, such that the predicted SMI prevalence went from 20% in 2021 to 50% by 2023 (interaction p = .01), whereas SMI remained relatively stable for other drug combinations, including those with OUD without kratom use, kratom without OUD, and neither OUD nor kratom.Conclusion: Over a short period of 3 years, SMI more than doubled among those with concurrent kratom use and OUD. At a time of strained US treatment systems, high overdose rates, and a mental health crisis, we stress the multiplicative association between kratom, opioid use disorder, and SMI.
Background: While physiological dependence on kratom (indicating tolerance and withdrawal) has been differentiated from kratom use disorder (KUD) in the West, the emphasis in Malaysia remains on kratom dependence. This has implications for treatment approaches.Objectives: This study was initiated to assess the extent to which medical practitioners treat patients with kratom dependence, their fields of specialization, their knowledge of kratom, and the treatment protocols used.Methods: An online questionnaire was distributed to approximately 17,000 Malaysian Medical Association (MMA) members, yielding 148 responses (0.9% response rate).Results: Male respondents comprised 58% of the sample, and 62% of physicians worked in public hospitals. Fifty-nine percent had treated patients for kratom dependence, with the majority having a background in psychiatry. Those treating kratom dependence had higher odds of being in public service (OR: 3.3: 1.64-6.56; p < .018), and had shorter mean duration of service (15.6 years), relative to the group that had not treated kratom dependence (18.3 years). Nearly 68% percent of those treating kratom dependence believed kratom to have similar effects as opioids and therefore prescribed treatments for kratom withdrawal that were designed for opioid withdrawal.Conclusions: Our findings suggest that opioid agonists are commonly used for the treatment of kratom withdrawal. However, kratom's distinct pharmacology relative to classical opioids suggests that treatment approaches developed for opioid withdrawal may not fully address the clinical features of kratom withdrawal.
Kratom use in the United States (US) has increased. Kratom is not federally scheduled; regulation is heterogenous and determined at the state level. Strategies include no regulation, bans and kratom consumer protection acts (KCPA) such as age limits, product purity or labeling requirements. Public health data informing these policies remain limited. This study aimed to compare rates of poison center (PC) reported kratom exposures, including those associated with severe medical outcomes and healthcare use, across US states with differing regulatory frameworks, and to characterize national trends in kratom exposures over time. Retrospective observational study of kratom exposures reported to the National Poison Data System from 2010 to 2023. All 50 US states and the District of Columbia. A total of 8919 kratom-related exposures were reported to PCs during the study period, including 5452 single-substance exposures (61%). Most cases involved adult males (69%), aged ≥18 years (8133; 91%). States were classified by kratom regulatory status into four categories: unrestricted (no regulations), KCPA, local restrictions (KCPA in 1 or more county, but no state regulation) or banned (retail sale illegal). The primary outcome was the incidence of severe medical outcomes defined as exposures coded by America's Poison Centers criteria as major effect (life-threatening or resulting in significant residual disability) or death. Secondary outcomes included rates of exposure, hospitalization and healthcare use (defined as hospital admission or evaluation in an emergency department, urgent care or primary care). Kratom exposures increased from 19 cases in 2010 to 1242 cases in 2023 [incidence rate ratio (IRR) = 69.0 compared with 2010; 95% confidence interval (CI) = 39.6-120; P < 0.001]. Severe medical outcomes increased from zero cases in 2010 to 158 cases in 2023; 2012 was the first year in which a severe outcome was reported (2023 IRR = 56.9 vs 2012; 95% CI = 14.7-221; P < 0.001). Overall, 13% of kratom exposures resulted in a severe medical outcome. Compared with states where kratom was banned, statistically significantly higher rates of exposures (IRR = 2.49; 95% CI = 1.89-3.28), severe medical outcomes (IRR = 3.19; 95% CI = 1.78-5.70), healthcare use (IRR = 2.44; 95% CI = 1.66-3.60) and hospitalization (IRR = 2.45; 95% CI = 1.81-3.30, P < 0.001) occurred (all P < 0.001). No statistically significant differences were identified between other regulatory categories. Kratom exposures and severe medical outcomes reported to United States poison centers are increasing nationally, though states with bans in place have experienced less pronounced increases.
Kratom (Mitragyna speciosa) has traditionally been used in Thailand; however, it was illegal. Following decades of prohibition, kratom was removed from Thailand's list of narcotics on 24 August 2021, effectively legalizing its use. This study aims to describe the frequency, clinical characteristics, and trends of kratom-related poison center calls before and after legalization. We conducted a retrospective review of data from the Ramathibodi Poison Center covering three 6-month periods: 24th of August, 2020 to 23rd of February, 2021; 24th of February, 2021 to the 23rd of August, 2021; and the 24th of August, 2021 to the 23rd of February, 2022. Patients with confirmed kratom exposure were included. Overall, kratom exposure-related phone calls involved 173 cases: 39, 38, and 96 cases in the 1st, 2nd, and 3rd periods, respectively. The mean and median ages of all patients were 29 years (SD 14.1 years) and 25 years (IQR 19-38 years), respectively. Most cases (84.4%) involved male patients, while most (∼60%) also co-ingested kratom with other substances. Tachycardia (43.4%) was the most common abnormal vital sign, and palpitations (35.8%) were the most common clinical manifestation. We compared the clinical characteristics of cases among the three periods, revealing no significant differences in age, sex, regions, co-ingestion, or clinical effects. The prevalence of acute dystonia decreased significantly after legalization (12.8%, 18.4%, and 6.3%, P = 0.008). However, cases in the 3rd period were admitted (37.5%) significantly more often than those in the previous two periods (15.8%, 10.3%; P = 0.001). Kratom-related calls increased by 2.5-fold after legalization, while consultation and hospitalization rates also rose. Most cases involved young males who used kratom with other substances. The types of symptoms reported before and after legalization remained largely consistent, with neurological and cardiovascular effects predominating. However, hospital admissions increased significantly following legalization. Following kratom legalization in Thailand, hospital admissions increased significantly. Continued poison center surveillance and regulatory oversight are essential for monitoring evolving patterns of kratom use and associated harms in the post-legalization era.
To assess the US lifetime and past-year prevalence of kratom Mitragyna speciosa use and its associations with mental health and DSM-5 substance use disorder (SUD). This study examined cross-sectional survey data collected from 169,408 non-institutionalized individuals aged 12 and older in US households between 2021 and 2024. Measures included kratom use, nonmedical use of cannabis, prescription drugs (opioids, sedatives/tranquilizers, stimulants), other drugs, mental health indicators (serious psychological distress, DSM-5 major depression, suicidal ideation), and DSM-5 SUD. Between 2021 and 2024, lifetime and past-year kratom use were highest among adults aged 21 to 34, 3.40% (95% CI: 3.17-3.65) and 1.01% (95% CI: 0.91-1.13), respectively. Among people who reported prior-to-past-year kratom use, most reported past-year cannabis (65.7%; 95% CI: 60.4-70.3) and had a past-year SUD (52.8%; 95% CI: 50.1-55.4), whereas an estimated 37.8% (95% CI: 37.2-47.3) experienced serious psychological distress. Similar results were observed for those who reported past-year kratom use. Multivariate logistic regression analysis revealed prior-to-past-year and past-year kratom use was associated with increased adjusted odds of past-year SUD (AOR: 4.36; 95% CI: 3.89-4.88 and AOR: 4.81; 95% CI: 3.99-5.80, respectively). Similar results were found for other substance use, DSM-5 major depression, and suicidal ideation. Over 5 million people in the United States used kratom in their lifetime, with the highest use at ages 21-34 years. Kratom use is increasing and strongly associated among individuals who use cannabis, have a DSM-5 SUD, and experience serious psychological distress. These findings reinforce a profile of individuals who use kratom, many with behavioral health symptoms, and need evidence-based treatment warranting consideration in clinical and policy efforts.
Kratom and kratom products are increasingly used in Western countries for pain management, mood disorders, and opioid withdrawal. Despite perceptions of safety, kratom can cause hepatotoxicity and clinically relevant herb-drug interactions, particularly with medications metabolized by cytochrome P450 (CYP) enzymes. We report a 45-year-old male with stable psychiatric conditions on nortriptyline and lisdexamfetamine, who developed mild, reversible liver enzyme elevations and supratherapeutic nortriptyline levels during chronic kratom use (raw, dry leaf, two tablespoons daily for five to six years). Initial labs showed aspartate aminotransferase (AST) 33 U/L, alanine aminotransferase (ALT) 70 U/L, alkaline phosphatase (ALP) 136 U/L, gamma-glutamyl transferase (GGT) 141 U/L, and nortriptyline 350 mcg/L. Dose reduction of nortriptyline partially corrected serum levels, but liver enzyme elevations persisted. Kratom discontinuation led to normalization of both liver function tests and nortriptyline levels within three weeks. This case illustrates two clinically important considerations: kratom-induced liver injury (KILI) and a CYP-mediated herb-drug interaction. The patient's use of raw leaf contrasts with commercial products, which may include concentrated extracts, 7-hydroxymitragynine (7OHMG)-enriched formulations, or ethanol-based preparations, potentially increasing hepatotoxicity and interaction risk. Even mild liver enzyme elevations in patients using kratom warrant evaluation, particularly with concurrent CYP-metabolized medications. Clinicians should educate patients about product variability, monitor liver function and drug levels, and consider temporary kratom discontinuation to assess causality. This case reinforces the growing evidence of kratom's hepatotoxic potential and the importance of integrating pharmacokinetic considerations into patient care.
Kratom ( Mitragyna speciosa ) is a psychoactive plant with stimulant, sedative, and analgesic properties, yet the mechanisms underlying its behavioral effects remain incompletely understood. In particular, it is unclear whether kratom's effects across behavioral domains are uniformly mediated by opioid receptor signaling. The present study used the planarian flatworm ( Dugesia dorotocephala ) to characterize the effects of kratom and to determine the extent to which these effects are opioid-dependent using the antagonist naloxone. In study 1, kratom produced dose-dependent reductions in locomotion and nociceptive responding, with higher doses nearly abolishing movement. In study 2, kratom significantly reduced locomotion, but this effect was not reversed by naloxone. In contrast, kratom-induced reductions in nociceptive curling were reversed by naloxone, indicating opioid receptor involvement. Together, these findings demonstrate a dissociation between opioid-dependent and opioid-independent effects of kratom, with analgesic effects mediated by opioid receptors and behavioral effects mediated by nonopioid mechanisms. These results highlight the multimodal pharmacology of kratom and support the use of planarians as a tractable model for investigating its neurobehavioral mechanisms.
Kratom, a medicinal Southeast Asian plant, gained interest in the United States for its analgesic and stimulant effects. Previous clinical studies characterized mitragynine and 7-hydroxy-mitragynine (7-OH-MTG) plasma pharmacokinetics following kratom tea and dried kratom leaf powder intake; however, to date, there are no kratom extract data. In the current study, mitragynine and 7-OH-MTG plasma pharmacokinetics are characterized in humans following increasing single doses (SD) and 15 multiple daily doses (MD) of concentrated kratom extract (39.5% mitragynine) containing 9.9, 29.6, and 59.2 mg mitragynine. Mean mitragynine plasma Cmax after single escalating doses increased dose-dependently, 32.8 ± 17.0, 93.2 ± 38.6, and 196 ± 77.4 ng/ml at a median Tmax of 1.3 h, with mean 7-OH-MTG Cmax of 6.8 ± 2.7, 13.7 ± 3.3, and 30.5 ± 12.2 ng/mL at a median Tmax of 1.3-1.7 h. Mean mitragynine plasma Cmax after 15 escalating multiple doses increased dose-dependently, 27.4 ± 10.9, 125 ± 79.7, and 277 ± 48.8 ng/mL at a median Tmax of 1.7-2.0 h, with mean 7-OH-MTG Cmax of 5.4 ± 1.9, 16.6 ± 6.1, and 33.9 ± 5.5 ng/mL at a median Tmax of 1.7-2.3 h. Cmax and AUC increased dose-dependently following SD and MD but were less than 1.4X greater than expected for both analytes and all doses based on strict dose proportionality. Half-lives were best reflected at higher doses due to the ability to measure low analyte concentrations longer but also suggested possible enzyme saturation. Higher 7-OH-MTG to mitragynine ratios were observed after multiple doses compared to SD and at lower compared to higher doses. These data indicate that concentrated kratom extracts may yield greater overall mitragynine exposure than dried kratom leaf powder or kratom tea preparations administered at comparable doses.
Psychological stress causes and deteriorates interstitial cystitis/painful bladder syndrome with urinary frequency, incontinence, bladder pain and urgency. The major alkaloid of kratom (Mitragyna speciosa), mitragynine, shows analgesic, anxiolytic, and smooth muscle relaxant effects. However, the effects of kratom leaf extract on stress-induced anxiety-like behavior, urinary bladder pain and urinary bladder dysfunction remain unknown. Therefore, this study aims to examine the effect of kratom leaf extract administration on anxiety-like behaviors, bladder pain, bladder contractile properties, and mast cell number in mice exposed to water avoidance stress. Male C57BL/6 mice were exposed to water avoidance stress (WAS) protocol for 10 consecutive days and compared with the stress-exposed mice receiving oral administration of kratom leaf extract (2.5 and 5 mg/kg of mitragynine) or solifenacin (10 mg/kg). Anxiety-like behaviors were assessed using open field test. Bladder pain sensitivity was evaluated with von Frey test, while voiding behavior was analyzed using voiding pattern analysis. Bladder contractility was examined using an in vitro organ bath technique, and urinary bladder mast cell infiltration was assessed by toluidine blue staining. Results show that mice receiving WAS had a reduction in the total duration and number of unsupported rearing behaviors, reduced voiding area, and increased bladder pain responses; however, these effects were reversed by treatment with kratom leaf extract (2.5 and 5 mg/kg of mitragynine). Interestingly, the WAS group also exhibited markedly increased tonic contractions in response to carbachol, a muscarinic agonist; these responses were attenuated in mice treated with kratom leaf extract (2.5 and 5 mg/kg) The enhanced tonic contractile response to carbachol was abolished by pre-incubation with ondansetron (a 5-HT₃ antagonist). The WAS group showed an increased total number of mast cells in the urinary bladder, which was reduced by treatment with kratom leaf extract at both 2.5 and 5 mg/kg. Our results indicate that treatment with kratom leaf extract attenuated chronic stress-induced bladder pain responses, voiding abnormalities, and mast cell numbers, and was associated with reduced contractile response to muscarinic stimulation, suggesting a potential modulatory effect on stress-induced bladder dysfunction.
Kratom laws vary widely across U.S. states, from Schedule I control to regulation or no policy. Limited evidence links these environments to kratom detection in fatal overdoses. This study examines the association between state kratom policy status and kratom-detected overdose deaths using State Unintentional Drug Overdose Reporting System (SUDORS) data. A retrospective ecological analysis using 2020-2024 SUDORS data from 45 jurisdictions reporting kratom detections. Jurisdiction-year observations were classified as controlled, regulated, or lacking statewide policy. Negative binomial regression with jurisdiction and year fixed effects and an offset for total overdose deaths estimated incidence rate ratios (IRRs). Standard errors were clustered by jurisdiction. Opioid-stimulant co-involvement was included as a covariate. Quasi-Poisson fixed-effects model assessed robustness. Compared with Schedule I controlled-substance states, kratom detection rates were significantly higher in regulated states (IRR 3.27; 95% CI 1.78-6.02) and in states without statewide policy (IRR 4.19; 95% CI 2.94-5.98). Quasi-Poisson estimates were similar. Kratom detection in fatal overdoses was more common in regulated and non-regulated states than in controlled-substance states. State policy context may influence kratom availability and detection. Ongoing monitoring and policy evaluation are needed.
Kratom (Mitragyna speciosa Korth.) has gained increasing global attention due to its traditional use, psychoactive properties, and emerging therapeutic potential; however, concerns regarding adulteration, substitution, and inconsistent quality of commercial products necessitate robust authentication strategies. This study aimed to integrate DNA barcoding and comprehensive chemical profiling to authenticate kratom variants and discriminate them from closely allied Mitragyna species for quality control and forensic applications. Nine DNA barcoding regions were analyzed, alongside chemical characterization using UHPLC, GC-MS, and LC-MS/QTOF. Among the tested loci, the internal transcribed spacer (ITS) and ITS2 regions exhibited the highest interspecific variation and effectively distinguished kratom from allied species. UHPLC and GC-MS analyses confirmed that mitragynine was exclusively detected in kratom variants, with Kan Khiao exhibiting the highest content (94.33 ± 0.14 mg/g) when quantified against the mitragynine standard using UHPLC analysis. LC-MS/QTOF profiling revealed an alkaloid-rich chemotype in kratom dominated by mitragynine and 7-hydroxymitragynine, whereas M. diversifolia, M. hirsuta, and M. rotundifolia showed distinct profiles enriched in phenolic acids and flavonoid glycosides. Multivariate analyses further identified procyanidin B1, datiscetin-3-O-rutinoside, mitragynine, and 7-hydroxymitragynine as key discriminatory markers. Overall, the combined molecular and chemical workflow provides a robust framework for kratom authentication, supporting regulatory monitoring, quality assurance, and forensic identification of kratom materials.
Kratom is an emerging drug of concern that poses significant challenges in perioperative care, but the public and many health professionals remain unaware of its use and effects. Patients may use kratom as a substitute for opioids or to increase focus or decrease anxiety, depending on the dose. Kratom binds with μ-opioid, α2-adrenergic, and serotonin receptors and has been associated with perioperative complications, including difficulty managing pain, hemodynamic instability, agitation, and withdrawal symptoms in patients undergoing surgery. Considering that 1.9 million Americans aged 12 years and older have used kratom, screening patients before surgery is important. Preoperative nurses can positively affect patient care by communicating a patient's use of kratom to the care team. With that knowledge, perianesthesia, intraoperative, and postoperative teams can be prepared for any untoward effects of kratom use across all perioperative settings.
Kratom is increasingly used in the United States for energy and self-management of pain and mood. While its active alkaloid, mitragynine, has partial μ-opioid receptor agonist activity, clinical data on its abuse potential remain limited. This study evaluated abuse-related outcomes following single and multiple doses of dried kratom leaf powder in healthy kratom-naive adults in a randomized, double-blind, placebo-controlled study. Healthy participants (n = 116) received a single oral dose or 15 consecutive daily doses of Mitra-Leaf kratom capsules (4 cohorts: 500-4000 mg dried leaf powder; equivalent to 6.65-53.2 mg mitragynine; n = 12-13 per cohort, n = 49 total) or placebo (n = 67). Subjective effects were assessed using the Drug Effects Questionnaire (DEQ). Opioid withdrawal symptoms were evaluated using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale (COWS). Abuse-related treatment-emergent adverse events (ARTEAEs) were recorded. DEQ responses were dose-related, except between the middle two dose levels with statistically significant increases in maximum effect and area-under-the-curve compared to placebo observed only at the highest single dose. DEQ responses decreased following repeated dosing. No participants met the threshold for clinically meaningful opioid withdrawal based on COWS or SOWS. ARTEAEs occurred more frequently at higher doses but were generally mild and resolved without sequelae. No serious adverse events or deaths were reported. Oral administration of kratom at tested doses was well tolerated and associated with modest, dose-related subjective effects, minimal withdrawal symptoms, and low ARTEAE rates. Findings support further research on kratom's safety and therapeutic potential, while emphasizing the importance of dose control and product standardization.
Kratom (Mitragyna speciosa) products have become widely available in diverse commercial formulations, raising increasing analytical and regulatory interest due to the presence of potent alkaloids such as mitragynine (MG), 7-hydroxymitragynine (7-OH), and mitragynine pseudoindoxyl (MGP). The accurate identification of these compounds is analytically challenging because kratom matrices contain numerous structurally related alkaloids and isomeric species that produce similar mass spectral features. In this study, an ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) workflow was developed to characterize kratom alkaloids in authentic leaf materials and 38 commercial kratom products representing multiple formulations. Chromatographic separation combined with accurate mass measurement and diagnostic MS/MS fragmentation enabled reliable differentiation of MG, 7-OH, MGP, and related isomers. Multiple overlapping chromatographic peaks were observed at m/z 415.2227, demonstrating that reliance solely on accurate mass or commonly monitored transitions such as m/z 415 → 190 can lead to false-positive identification of 7-OH in complex botanical matrices. Application of the multicriteria confirmation strategy revealed substantial variability in alkaloid composition across commercial products, including the presence of 7-OH and MGP in several tablet and capsule formulations. Untargeted metabolomic profiling further distinguished kratom plant extracts, including the authentic leaf materials, from processed products enriched in specific alkaloids. These results highlight the importance of integrating chromatographic resolution with orthogonal MS/MS criteria for reliable identification of kratom alkaloids and provide an analytical framework for the characterization of complex botanical products.
In October 2025, the Alabama Poison Information Center and local addiction medicine providers identified a cluster of cases involving liquid products marketed as containing kava associated with opioid-like withdrawal symptoms. Kava is not typically associated with physical dependence, raising concern for opioid-active substances. Five unique retail products were submitted for laboratory analysis. Three underwent quantitative ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) testing for kavalactones, kratom alkaloids, and related semisynthetic derivatives, with additional screening for 260 substances. Two products underwent qualitative gas chromatography-mass spectrometry (GC-MS) testing for mitragynine and kavalactones. Qualitative GC-MS detected both mitragynine and kavalactones in one product, while another contained mitragynine with no detectable kavalactones. Quantitative UPLC-MS/MS identified both kavalactones and kratom alkaloids in three products, with mitragynine pseudoindoxyl predominating at concentrations of 0.16-0.21 mg per bottle. Detection of kratom alkaloids and related semisynthetic derivatives in products labeled as kava may explain the observed opioid-like withdrawal. Mitragynine pseudoindoxyl, which has greater opioid activity than mitragynine and 7-hydroxymitragynine, was identified as the predominant kratom-related compound. Unrecognized exposure to opioid-active kratom compounds may occur through products marketed as kava, highlighting the need for improved surveillance and increased awareness.
Kratom has a long history of use internationally. New formulations and extracts have recently come to the market and there has been an increase in interest and news around kratom and its alkaloids. This paper updates the epidemiology and clinical outcomes from kratom exposures reported to US Poison Centers. We analyzed kratom exposures reported to US Poison Centers from January 1, 2016 through July 31, 2025 to describe the epidemiology and compare the more recent exposures in 2025 to those reported before 2025. There were 13,194 exposures over the period. There was a slow increase and steady report of exposures from 2016 through 2024, with an increase in 2025. Males accounted for 68% of the population and the mean age was 32 years. Most patients (11,205, 85.0%) were either in or referred to a healthcare facility. Of these, 16.5% were admitted to the intensive care unit, 15.1% to a non-intensive care unit, 6.2% to a psychiatric facility, and 46.1% were discharged from the emergency department. There were 219 (1.6%) deaths (43 single-substance and 176 polysubstance) and 1324 (10%) major effects (potentially life-threatening signs or symptoms) reported. We identified a difference in the distribution of outcomes comparing pre-2025 and 2025 exposures for single-substance exposures but not polysubstance. Clinical effects were largely similar over time. There has been a significant increase in kratom exposures reported to US Poison Centers, but the overall outcomes have remained similar. Further investigation should be performed to identify the causes of the increase.
Monoterpene indole alkaloids (MIAs) are a major class of plant natural products with important pharmaceutical activities, yet the biosynthetic pathway to their universal precursor, strictosidine, has been fully elucidated in only Catharanthus roseus. In kratom (Mitragyna speciosa), only the first and last steps of strictosidine biosynthesis were previously known. Here, we applied multiplex pathway engineering in yeast to accelerate the discovery, reconstruction, and optimization of the kratom strictosidine pathway. Iterative multiplex integration and screening identified 13 functional kratom genes and enabled rapid validation of functional pathway modules, thereby completing the kratom strictosidine pathway from geranyl pyrophosphate and tryptophan. We also identified a vacuolar secologanin transporter, MsNPF2.6, which increased strictosidine production by 62% in yeast. Pathway optimization through the incorporation of nepetalactol-producing enzymes from other plants further supported strictosidine production in yeast from fed geraniol and tryptophan. These results establish the strictosidine pathway in kratom and highlight multiplex engineering as a powerful platform for rapid plant pathway discovery and optimization.
Kratom (Mitragyna speciosa) is an unregulated herbal supplement increasingly associated with severe toxicity. Concentrated liquid formulations pose risks, with emerging reports of seizures, hepatotoxicity, and arrhythmias. A previously healthy 24-year-old woman ingested a highly concentrated kratom extract and developed seizure-like activity followed by pulseless monomorphic ventricular tachycardia. She underwent approximately 45 minutes of resuscitation, including multiple defibrillations, dual-sequential shocks, amiodarone, lidocaine, magnesium, calcium, sodium bicarbonate, potassium repletion, epinephrine, and esmolol. Persistent instability prompted consultation with cardiology and cardiothoracic surgery, and she was cannulated for venoarterial extracorporeal membrane oxygenation (ECMO) in the emergency department. Lab studies showed profound hypokalemia, acidosis, and elevated lactate. Urine toxicology confirmed mitragynine. She stabilized on ECMO, was decannulated on hospital day two, extubated on day three, and discharged home neurologically intact on day seven. Concentrated kratom extracts can precipitate life-threatening ventricular arrhythmias in previously healthy individuals. Emergency physicians should consider kratom in unexplained cardiac arrests and recognize the role of advanced support, including ECMO, in refractory toxicologic arrests.
Kratom (Mitragyna speciosa) is a plant-derived supplement increasingly used in the United States for chronic pain and mood elevation due to its opioid-like effects. While systemic side effects have been described, cutaneous manifestations have rarely been reported. We report a case of striking photodistributed dyspigmentation in a chronic kratom user, with a detailed description of the histologic and elemental analysis findings. A 37-year-old Soldier taking kratom for lower back pain presented with asymptomatic blue-gray pigmentation involving his face, neck, and dorsal hands. Biopsy revealed pigment-laden macrophages within the superficial dermis, a mild perivascular and periadnexal lymphohistiocytic infiltrate, and a slightly thickened basement membrane. Special stains confirmed the pigmented particles as melanin-like. Scanning electron microscopy with energy-dispersive X-ray analysis (SEM-EDXA) demonstrated sulfur-containing material, consistent with phaeomelanin and/or a drug metabolite melanin-like complex. This case expands the clinicopathologic understanding of kratom-associated dermatoses and illustrates the utility of SEM-EDXA in identifying exogenous or drug-induced pigmentation.
Kratom (Mitragyna speciosa) has gained increasing interest due to its unique leaf alkaloids with pharmacological potential. Comparisons of climate conditions in Florida production areas with those in the plant's native habitat in Southeast Asia indicate a need to better understand how light quality, particularly ultraviolet (UV)-B radiation, influences plant growth and alkaloid biosynthesis. This study evaluated the effects of far-red (FR) light supplementation and end-of-day (EOD) UV-B exposure on plant growth, photosynthetic performance, and leaf alkaloid content of kratom. Plants were grown under controlled-environment conditions under five light treatments: white (W) light alone; W plus 1 or 2 h of EOD UV-B exposure; and W supplemented with FR light combined with 1 or 2 h of EOD UV-B exposure. Total photosynthetic photon flux density (PPFD) was maintained at 300 µmol·m-2·s-1, with additional supplemental FR and EOD UV-B provided at 90 and 0.3 µmol·m-2·s-1, respectively. Plant growth, photosynthesis, and alkaloid content were analyzed. Low-dose EOD UV-B had minimal effects on plant architecture and leaf growth, but slightly reduced leaf biomass and photosynthetic capacity. Extending EOD UV-B exposure from 1 to 2 h reduced the stem caliper by 20%, branching by 14%, and new leaf area by 14%. Supplementation with FR at 30% of total PPFD induced a shade-avoidance response, increasing plant height by 58% to 76% while reducing leaf number, photosynthesis, and biomass. Corynantheidine concentration in leaves increased by 175% under W plus 1 h of EOD UV-B, whereas speciociliatine, mitraciliatine, and isopaynantheine decreased in aging leaves. Light-quality-induced stress can modify alkaloid accumulation in kratom, and these responses must be carefully balanced against reductions in growth and biomass. These findings improve understanding of environmental regulation of kratom alkaloid biosynthesis and provide a basis for designing lighting strategies to optimize both biomass production and the accumulation of desirable alkaloids.