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Piper methysticum, known as “kava”, is a plant endemic to and historically consumed in the Pacific islands. The roots contain psychoactive kavalactones with sedating and anxiolytic effects. While often marketed for anxiety or as a safe alcohol alternative, dermopathy and more rarely hepatotoxicity are well described with heavy use. Reports of withdrawal are rare. The leaves of Mitragyna speciosa, also referred to as “kratom”, contain psychoactive alkaloids with interactions at μ and δ-opioid receptors. Kratom is commonly used for its stimulant and opioid-like effects, for which dependence and withdrawal are much more well documented. A 45-year-old man presented to the emergency department (ED) with auditory and visual hallucinations, anxiety, insomnia, and diffuse muscle jerking. He had been heavily using a supplemental beverage containing both kava and kratom, but stopped several days prior. His primary physician initiated buprenorphine therapy for suspected kratom withdrawal. Bedside evaluation in the ED was concerning for ongoing GABAergic withdrawal in the setting of kava use. Phenobarbital was given with significant improvement in symptoms, with eventual transition to diazepam. He was discharged home several days later in good condition. Given the increasing popularity of herbal supplements including kratom, and more uncommonly kava, clinicians should be aware of their potential for abuse, dependence and severe withdrawal syndromes. Kratom may be managed in a fashion analogous to that of an opioid. While kava's pharmacologic properties remain poorly understood, withdrawal may be severe enough to warrant hospitalization. Phenobarbital or benzodiazepines may be considered as a potential therapeutic approach. •Despite centuries of use, kava's pharmacologic and toxicologic properties remain poorly understood.•Mechanisms may include GABAA potentiation, DA and NE reuptake inhibition, Ca2+ and Na+ channel block, and MAO-B inhibition.•Withdrawal may mimic a syndrome similar to ethanol. Treatment with phenobarbital or benzodiazepines may be effective.

Purpose of Review We apply the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for substance use disorders (SUDs) to the herbal product kratom. Similarities and differences between kratom use disorder (KUD) and other SUDs are explored, along with assessment, diagnostic, and therapeutic recommendations for KUD. Recent Findings Literature reports of “kratom addiction” or KUD rarely specify the criteria by which patients were diagnosed. Individuals meeting DSM-5 KUD criteria typically do so via tolerance and withdrawal, using more than intended, and craving, not functional or ​psychosocial disruption, which occur rarely. Most clinicians who use medication to treat patients with isolated KUD select buprenorphine formulations, although there are no controlled studies showing that buprenorphine is safe or efficacious in this patient population. Summary Diagnosis and treatment decisions for KUD should be systematic. We propose an algorithm that takes into consideration whether KUD occurs with comorbid opioid use disorder.

Kratom (Mitragyna speciosa Korth.) is widely use worldwide despite its addictive potential. Although psychostimulant use has been linked to occurrence of endoplasmic reticulum (ER) stress, data is lacking on how regular kratom use affects ER stress. This case-control study first determined differences in ER stress sensor protein expression (BiP, sXBP1, ATF4, CHOP, JNK, and p-JNK) between regular kratom users and healthy controls. Second, it evaluated the association between kratom use characteristics, targeted ER stress sensor protein expression, and \"kratom use disorder\" diagnosed with Diagnostic and Statistical Manual for Mental Disorders 5th Edition (DSM-5) among regular kratom users. In total, 60 regular kratom users and 50 healthy control-group participants were recruited and administered a sociodemographic and clinical characteristics questionnaire. While participants who used kratom were also administered a kratom use characteristics questionnaire. Blood samples were collected from all participants, and targeted ER stress sensor protein expression was determined via Western blot analysis. The study's findings revealed first that kratom users registered significantly higher protein expression in all targeted ER stress sensors compared to the control group. Second, higher protein expression of CHOP (B = 5.061, standard error [SE] = 2.547, Wald = 3.948, adjusted odds ratio [AOR] = 5.382, 95% confidence interval [CI] = 1.071 to 9.656, p = 0.047) and p-JNK (B = 5.795, SE = 2.635, Wald = 4.544, AOR = 17.025, 95% CI = 1.395 to 24.123, p = 0.017) increased the odds of kratom use disorder occurrence. Kratom use characteristics and other ER stress sensor protein expression were not associated with kratom use disorder. Regular kratom use may induce protracted ER stress, leading to the decompensation of the unfolded protein response to maintain ER homeostasis. This effect may be linked to kratom use disorder occurrence.

Kratom is a widely used Asian botanical that has gained popularity in the United States due to a perception that it can treat pain, anxiety, and opioid withdrawal symptoms. The American Kratom Association estimates 10–16 million people use kratom. Kratom‐associated adverse drug reactions (ADRs) continue to be reported and raise concerns about the safety profile of kratom. However, studies are lacking that describe the overall pattern of kratom‐associated adverse events and quantify the association between kratom and adverse events. ADRs reported to the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021 were used to address these knowledge gaps. Descriptive analysis was conducted to analyze kratom‐related adverse reactions. Conservative pharmacovigilance signals based on observed‐to‐expected ratios with shrinkage were estimated by comparing kratom to all other natural products and drugs. Based on 489 deduplicated kratom‐related ADR reports, users were young (mean age 35.5 years), and more often male (67.5%) than female patients (23.5%). Cases were predominantly reported since 2018 (94.2%). Fifty‐two disproportionate reporting signals in 17 system‐organ‐class categories were generated. The observed/reported number of kratom‐related accidental death reports was 63‐fold greater than expected. There were eight strong signals related to addiction or drug withdrawal. An excess proportion of ADR reports were about kratom‐related drug complaints, toxicity to various agents, and seizures. Although further research is needed to assess the safety of kratom, clinicians and consumers should be aware that real‐world evidence points to potential safety threats.

Background “Kratom” commonly refers to the botanical Mitragyna speciosa , native to Southeast Asia, which is increasingly used globally for its unique pharmacological effects. Motives for using the whole plant material or kratom-derived products include self-management of pain, mental health disorders, symptoms related to substance use disorders, and/or to increase energy. In the United States, kratom products have varying alkaloid content, potencies, and marketing profiles. There is little regulatory oversight over kratom, as it is currently not approved as a dietary supplement by the Food and Drug Administration. This results in substantial variability in labeling of kratom products and the product information provided to consumers. Methods In January 2023, we evaluated the American Kratom Association’s Good Manufacturing Practices (GMP) qualified vendors’ websites ( n  = 42) using the well-established and validated DISCERN instrument to examine the quality of health information provided to consumers. DISCERN contains 15 five-point Likert-scale questions on specific criteria, with the highest possible score being 75, indicating that all the DISCERN criteria have been fulfilled by the website (i.e., the highest quality information is provided to consumers). Results The mean DISCERN score for all evaluated online kratom vendors was 32.72 (SD = 6.69; score range 18.00–43.76). Overall, vendors scored higher on DISCERN questions assessing the website’s reliability, as vendors typically provided clear information for consumers about product availability, purchasing, shipping, etc. On average, vendors scored poorly on the DISCERN section pertaining to the quality of the health information provided. Information on kratom’s potential risks and benefits was particularly insufficient. Conclusions Consumers require high quality information in order to make informed decisions concerning use, which entails disclosure of known risks and potential benefits. The online kratom vendors evaluated in this study should consider enhancing the quality of health information provided, especially information regarding kratom’s risks and benefits. Further, consumers should be made aware of current knowledge gaps related to kratom’s effects. Clinicians must also be aware of the lack of evidence-based information available to their patients who use kratom or are interested in using kratom products, in order to facilitate educational discussions with them.

As an emerging toxic recreational drug, kratom use has been associated with a range of adverse effects, but reports of structural changes in the central nervous system are rare. We report a case of a young man in his 20s with a history of anxiety and depression who presented with an altered mental status and anterograde and retrograde amnesia following kratom use. His labs showed elevated alanine aminotransferase and ammonia levels, and his MRI revealed bilateral hippocampal T2 hyperintensity signal changes. Following cessation of kratom and supportive care, the patient improved. This case highlights the importance of considering kratom as a potential cause of neurological symptoms in patients presenting with an altered mental status due to toxic ingestion.

Kratom is an herbal product derived from Mitragyna speciosa which, depending on the dose, has stimulant and opioid-like effects and is increasingly being used recreationally to self-medicate symptoms of anxiety and depression. This case describes a man in his 30 s who presented to a community drug and alcohol service seeking support for problematic Kratom use, which he started using to try and manage obsessive-compulsive disorder symptoms and low mood. Despite attempts to reduce his use, he was unable to discontinue Kratom use independently. Initiation of low-dose sublingual buprenorphine led to complete abstinence within 3 weeks. This case highlights not only the potential use of low-dose buprenorphine to manage Kratom withdrawal but also the complexity in managing co-existent mental health disorders in addiction services, emphasising the importance of psychiatry within a multidisciplinary approach.

Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.

•Two postmortem cases are compared with regard to the role of mitragynine in the fatalities.•A significant difference could be seen in the absolute concentrations of mitragynine detected for the two cases.•A significant difference could be seen in the relative concentrations of mitragynine to its diastereomers between the two cases.•Mitragynine was not the direct cause of death in either of the two cases, despite an extremely high blood mitragynine concentration in one of the two. Two cases of fatalities are reported of which the recreational use of Mitragyna speciosa (“kratom”) could be confirmed. One of these cases presents with one of the highest postmortem mitragynine concentrations published to date. Our results show that even extremely high mitragynine blood concentrations following the consumption of kratom do not necessarily have to be the direct cause of death in such fatalities as a result of an acute overdose. The two cases are compared with regard to the differences in mitragynine concentrations detected and the role of mitragynine in the death of the subjects. Irrespective of the big differences in mitragynine concentrations in the postmortem blood samples, mitragynine was not the primary cause of death in either of the two cases reported here. Additionally, by rough estimation, a significant difference in ratio of mitragynine to its diastereomers in the blood and urine samples between the two cases could be seen.