<unk>  may cause many adverse effects and in November 2017 the FDA issued a public health advisory for the drug. The side effects of kratom appear to be dose-dependent and are more common with doses that exceed 8 g. While the incidence of adverse effects in people who use kratom is unknown, a 2019 review of 935 kratom exposures reported to U.S. poison control centers over a seven-year period listed the following signs and symptoms: agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), confusion (8.1%), seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%). The study also reported two deaths and four cases of neonatal abstinence syndrome. A different 2019 review listed as common side effects: decreased appetite, anorexia, weight loss, temporary erectile dysfunction, insomnia, sweating, hyperpigmentation, hair loss, tremor, and constipation. Kratom products in the U.S. are commonly used in doses ranging from 2–6 g of dried leaf per dose, and doses exceeding 8 g are relatively uncommon. However, there is no standard dosing system as kratom products may vary greatly in potency. At relatively low doses (1–5 g of raw leaves), at which there are mostly stimulant effects, side effects include contracted pupils and blushing; adverse effects related to stimulation include anxiety and agitation, and opioid-related effects like itching, nausea, loss of appetite, and increased urination begin to appear. At moderate to high doses (5–15 g of raw leaves), at which opioid effects generally appear, additional adverse effects include tachycardia (an increased stimulant effect) as well as the opioid side effects of constipation, dizziness, hypotension, dry mouth, and sweating. Long term use of high doses of kratom may lead to development of tolerance, dependence, and withdrawal symptoms, including loss of appetite, weight loss, decreased sexual drive, trouble sleeping, muscle spasms, muscle and bone pains, jerky movement, watery eyes, hot flushes, fever, diarrhea, restlessness, anger, and sadness. This may lead to resumption of use. Frequent use of high doses of kratom may cause tremors, anorexia, weight loss, seizures, and psychosis. However, in case reports associating kratom use with psychosis, it remains unclear whether kratom use directly caused psychosis or simply unmasked the condition. Serious toxicity is relatively rare and generally appears at high doses or when kratom is used with other substances. Herb-drug interactions may result when kratom is combined with alcohol, sedatives, benzodiazepines, opioids, caffeine, cocaine, yohimbine, or monoamine oxidase inhibitors (MAOIs). Rhabdomyolysis is one of the rare complications of this herb at high dosage. In July 2016, the Centers for Disease Control issued a report stating that between 2010 and 2015, US poison control centers received 660 reports of exposure to kratom. Medical outcomes associated with kratom exposure were reported as minor (minimal signs or symptoms, which resolved rapidly with no residual disability) for 162 (24.5%) exposures, moderate (non-life-threatening, with no residual disability, but requiring some form of treatment) for 275 (41.7%) exposures, and major (life-threatening signs or symptoms, with some residual disability) for 49 (7.4%) exposures. Overall, 92.6% of outcomes were resolved with no residual disability. One death was reported in a person who was exposed to the medications paroxetine (an antidepressant) and lamotrigine (an anticonvulsant and mood stabilizer) in addition to kratom. For 173 (26.2%) exposure calls, no effects were reported, or poison center staff members were unable to follow up regarding effects. A 2019 report from the American Association of Poison Control Centers (AAPCC) stated that kratom use was increasing rapidly, with 1807 kratom exposures and a 52-fold increase occurring over the years 2011 to 2017. Most exposures occurred intentionally by adult males in their homes, with 32% of the incidents requiring admission to a health care facility and half of the admissions as a serious medical condition. Multiple-substance exposures were associated with a higher number of hospitalizations than single-substance exposures, and involved 11 deaths, including two due to kratom alone. Postmortem toxicology testing detected multiple substances for almost all those who died, with fentanyl and fentanyl analogs being the most frequently identified co-occurring substances. Overdoses of kratom are managed similarly to opioid overdoses, and naloxone can be considered to treat an overdose that results in a reduced impulse to breathe, despite mixed results for its utility, based on animal models. From October 2017 to February 2018 in the United States, 28 people in 20 different states were infected with salmonella, an outbreak occurring from the consumption of contaminated pills, powder, tea or unidentified sources of kratom. An analytical method using whole genome sequencing applied to samples from the infected people indicated that the salmonella outbreak likely had a common kratom source. Respiratory depression Respiratory depression is the leading cause of death from opioid use. Although evidence is sparse, the risk from respiratory depression caused by taking<unk>  appears to be low, but the Food and Drug Administration listed respiratory depression as a concern. A 2018 review found that the alkaloids in kratom do not induce respiratory depression. Liver toxicity In rare cases, though with a dangerous delay, kratom use has been linked to acute liver injury with symptoms of abdominal discomfort, dark urine, itching and jaundice. Liver injury has been reported with a latency (time from first use to onset of symptoms) of median 20.6 days. Reported liver biopsies tend to show cholestasis, however blood biomarkers can show a range of cholestatic, mixed, or hepatocellular injury pattern. The majority of users do not seem to develop liver injury, and it is unclear which users are at heightened risk. The mechanism by which kratom causes liver damage in some people is unknown and poorly studied, but a model has been proposed. Death Kratom overdose is a subject of concern in many countries because of the rising number of hospitalizations and deaths in which chronic kratom use is a contributing factor. According to clinical reviews, a kratom overdose can cause liver toxicity, seizures, coma, and death, especially when in combination with excessive alcohol use. Between 2011 and 2017, forty-four deaths were kratom-related. However many cases could not be fully assessed because of limited information. People who died from kratom use typically have taken it in combination with other substances, or have underlying health conditions. Over 18 months in 2016 and 2017, 152 overdose deaths involving kratom were reported in the United States, with kratom as the primary overdose agent in 91 of the deaths, and 7 with kratom being the only agent detected. Nine deaths occurred in Sweden during 2010–11 relating to use of Krypton, a mixture of kratom, caffeine and O-desmethyltramadol, a prescription opioid analgesic.
Mitragyna speciosa
Craniopagus parasiticus
Piedraia hortae
Cedecea davisae
Ephedra distachya
Arcanum joviale
Gongylonema pulchrum
Cerbera odollam