Psychotria Viridis extract (chacruna) • Mitragyna Speciosa extract (kratom) • Salvia extract.
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Below is general information about the effectiveness of the known ingredients contained in the product Mexican Haze. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of Salvia divinorum.
Below is general information about the safety of the known ingredients contained in the product Mexican Haze. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY UNSAFE ...when used orally. Short-term use of kratom, especially in combination with other substances, has been associated with cases of intrahepatic cholestasis, rhabdomyolysis, seizure, encephalopathy syndrome, and death (27133,95797,95798,99182,103216,104634,104637,108758,108760,108763)(108764,108765,113069). Long-term use of kratom has been associated with tolerance and withdrawal symptoms including abdominal pain, aggression, agitation, anxiety, diarrhea, insomnia, muscle aches and spasms, nausea and vomiting, restlessness, shakiness, and tremors (27115,27125,27130,104637,108757,113061,113067,113079,113080). There is insufficient reliable information available about safety of kratom when applied topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
There have been multiple case reports of neonatal abstinence syndrome in the infants of those who used kratom during pregnancy (100503,100504). Animal research suggests that kratom crosses the placenta (100506).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY UNSAFE ...when used orally or by inhalation. Salvia divinorum contains a potent hallucinogen and has been shown to cause serious adverse effects including slurred speech, confusion, paranoia, depersonalization, blunted affect, hallucinations, and psychosis (7350,7351,15820,15821,72901,100001,100002).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Mexican Haze. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.
 Details
Kratom contains mitragynine, a mu-receptor agonist that may cause respiratory depression. Although results from animal research suggest that mitragynine causes less respiratory depression than the CNS depressant codeine (27130), fatalities have been reported for patients who ingested a combination of kratom and O-desmethyltramadol, another mu-receptor agonist (27119,27120). Additionally, observational research suggests that adverse effects such as drowsiness and coma are more likely to occur in individuals taking kratom in combination with agents such as opioids and sedatives (104637). Theoretically, ingesting kratom along with other CNS depressants can increase the risk of adverse effects, including drowsiness, coma, and/or severe or fatal respiratory depression.
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Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.
Details
In vitro research suggests that kratom extract inhibits the activity of CYP1A2 (27134). In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP1A2-mediaed metabolism of ziprasidone which consequently increased systemic exposure to serotonin (113059).
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Theoretically, kratom might increase the levels of drugs metabolized by CYP2C19.
Details
In vitro research shows that kratom extract weakly inhibits CYP2C19 enzyme activity (27134).
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Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Details
In vitro research suggests that kratom extract inhibits CYP2D6 enzyme activity (27134). However, human research shows that a single low dose of kratom tea 2 grams does not inhibit CYP2D6 activity. However, this kratom dose is lower than what is normally taken for psychoactive effects (113083). In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP2D6-mediated metabolism of buspirone and consequently increased systemic exposure to serotonin (113059). In another case, a 37-year-old male stable for 15 years on amitriptyline presented with anticholinergic symptoms including xerostomia, dry eyes, and constipation, along with mildly elevated bilirubin and liver enzymes after taking progressively higher doses of up to 14 grams of kratom daily for 12 weeks. It was hypothesized that the adverse effects of amitriptyline were precipitated by CYP2D6 inhibition by kratom (113085).
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Theoretically, CYP3A4 inhibitors might increase the concentrations and clinical effects of kratom's active metabolites mitragynine and 7-hydroxymitragynine.
Details
Animal research suggests that CYP3A4 inhibition with ketoconazole reduces the metabolism and clearance of kratom, increasing the peak plasma concentration (Cmax) of the active metabolite mitragynine by 130%, time to reach maximum plasma concentration (Tmax) from 1 to 2.6 hours, and area under the concentration-time curve (AUC) by 120%. Additionally, CYP3A4-mediated conversion of mitragynine into 7-hydroxymitragynine increases systematic exposure by 130%. However, other CYP isoforms are likely involved in this conversion. CYP3A4 inhibition could lead to increased adverse effects and mu-opioid-receptor-mediated behavioral effects associated with kratom and its metabolites (113065).
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Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity (27134). A pharmacokinetic study in adults shows that taking kratom tea 2 grams modestly increases the plasma concentration time-curve (AUC) and maximum concentration (Cmax) of CYP3A4 probe midazolam by 40-50% and its CYP3A4-mediated metabolites 18-27%. However, a lack of change in the half-life of midazolam and a simulation of the kratom-midazolam interaction suggest that kratom inhibits CYP3A4 enzymes in the small intestine but not the liver (113083). Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom (99810). In another case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It is hypothesized that CYP3A4 inhibition by kratom reduced metabolism of desvenlafaxine, trazodone, and ziprasidone and consequently increased systemic exposure to serotonin (113059).
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Theoretically, taking kratom in combination with modafinil may increase the risk of seizures.
Details
A 43-year-old male patient experienced generalized tonic-clonic seizures after adding modafinil 100 mg to his chronic ingestion of kratom tea four times daily to further improve alertness and as a self-treatment for opioid withdrawal (27127). The exact mechanism by which this interaction may occur is unknown.
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Taking kratom in combination with naltrexone might precipitate withdrawal.
Details
Animal research shows that, while naltrexone does not antagonize the primary kratom alkaloid mitragynine, it does inhibit the behavioral effects of the metabolite 7-hyroxymitragynine by antagonizing its binding at the mu-opioid receptor (113070). In humans, taking naltrexone has precipitated withdrawal from kratom. In one case, a patient chronically consuming kratom developed agitation, hallucinations, and delirium within about 2 hours of beginning oral naltrexone therapy (114754). In another case, a 38-year-old male who was admitted to a residential rehabilitation treatment program for polysubstance abuse experienced opioid withdrawal after administration of intramuscular naltrexone. Although the patient reported discontinuing kratom, continued use was confirmed through positive urine mitragynine tests. Manufacturer guidance states that patients should be opioid-free for a minimum of 7-10 days prior to initiating treatment with naltrexone; this case report suggests that kratom use should be given similar consideration (108761).
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Theoretically, taking kratom in combination with quetiapine may increase levels and adverse effects of quetiapine.
Details
A 27-year-old male was found deceased due to neuroleptic malignant-like symptoms after concomitant consumption of quetiapine and kratom. Although it did not appear that he had consumed large quantities of the medication, he was found to have a lethal plasma level of quetiapine (99810). It is hypothesized that kratom inhibited cytochrome P450 (CYP) 3A4, the primary metabolic pathway for quetiapine (99810). Also, a 36-year-old male presented to the emergency department with serotonin syndrome and QT interval prolongation after concomitant use of quetiapine, venlafaxine, and kratom. It is hypothesized that kratom may have inhibited the metabolism of both venlafaxine and quetiapine (108766).
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Theoretically, taking kratom in combination with serotonergic drugs may increase levels of serotonin, increasing the risk of serotonin syndrome.
Details
A 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited the cytochrome P450 3A4-, 2C9-, 2D6-, and 1A2-mediated metabolism of several of these serotonergic medications, consequently increasing systemic exposure to serotonin (113059).
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Theoretically, taking kratom in combination with venlafaxine may increase levels and clinical effects of venlafaxine.
Details
A 36-year-old male presented to the emergency department with serotonin syndrome and QT interval prolongation after concomitant use of venlafaxine, quetiapine, and kratom (108766). It is hypothesized that kratom may have inhibited the cytochrome P450 (CYP) metabolism of both venlafaxine and quetiapine (108766).
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Below is general information about the adverse effects of the known ingredients contained in the product Mexican Haze. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, kratom is possibly unsafe.
Topically, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Constipation, dependence (chronic use), dry mouth, frequent urination, nausea, tongue numbness, and vomiting.
Serious Adverse Effects (Rare):
Orally: Cardiac arrest, death, encephalopathy syndrome, hallucinations, hypertension, hypothyroidism, insomnia, liver damage, rhabdomyolysis, respiratory depression, seizures, serotonin syndrome, and tachycardia. However, a definite causal link between kratom and most of these serious adverse effects has not yet been confirmed.
Cardiovascular
...Orally, kratom can cause tachycardia and changes in blood pressure, especially when used in doses of 8 grams or more (95819).
In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 45% of cases reported cardiovascular effects (108565). Patients who have called poison control centers in the United States, Thailand, and British Columbia report stimulant effects including tachycardia and hypertension after chronic and acute kratom use (95796,95797,95798,95818,101707,104633,104636,104637,113075).
Additionally, a large analysis of adverse effect reporting databases suggests that mitragynine, a constituent of kratom, is associated with an increased risk of ventricular arrhythmias and cardiac arrest, but not QTc prolongation. The validity of this study is limited by voluntary reports and potential for multiple co-ingestions or co-exposures in individual reports (114575).
One observational study reported that regular kratom use, with an estimated daily intake of mitragynine 7.06 mg/kg/day, was associated with at least an 8-fold increase in the odds of presenting with sinus tachycardia when compared with non-kratom users. However, there was no difference in the odds of having other ECG abnormalities (104636). In this study, kratom use was associated with an increased odds of borderline QTc intervals, but not prolonged QTc intervals. The highest odds occurred in those who started using kratom after age 18, had used kratom for more than 6 years, or those who had used kratom within 3 hours of the ECG (104636). In regular kratom users, a case series conducted to analyze serum mitragynine levels with respect to cardiovascular functioning found that higher serum mitragynine levels (i.e., at least 9.6 mg/L) were associated with prolongation of the QT interval and such effects were found to be dose-dependent (108566).
In one case report, an otherwise healthy, 35-year-old male with a history of opioid use disorder presented with cardiac arrest after recently consuming kratom tea multiple times per day. No other substance use was identified on toxicology screening or via patient report (101706). Another case of cardiac arrest with ventricular fibrillation has been reported in a 24-year-old male who reported long-term use of kratom (dose and frequency unknown). While the patient had a history of polysubstance abuse, his serum and urine drug screens were negative for opiates, benzodiazepines, amphetamines, and cocaine (103215). Similarly, a 32-year-old male with a history of substance abuse, depression, and obesity presented after collapsing due to seizure with acute mitragynine intoxication. The patient also presented with cardiomegaly with left ventricular hypertrophy, hepatomegaly, cerebral edema, and pulmonary edema. Postmortem toxicology analysis of blood, organs, and gastric contents were negative for all illicit and prescription drugs except for the kratom components mitragynine and 7-hydroxymitragynine (113069).
There have been two case reports of 54-year-old adults using kratom regularly for one year who developed stimulatory effects and a large hemorrhagic stroke. In both cases, the development of these adverse effects occurred immediately after the transition to a different kratom product (101705,108759). In one case, the product was found to be adulterated with phenethylamine (PEA), an amphetamine-like chemical, which was considered the likely cause of these effects (101705).
Dermatologic ...A case of photodistributed hyperpigmentation on the arms and face has been reported in a 54-year-old male who regularly consumed powdered kratom in orange juice 3-4 times daily for up to 5 years (113073). Another case of progressive, drug-induced photodistributed hyperpigmentation on the neck, chest, arms, and legs was reported in a 56-year-old female who took 4-5 doses of kratom daily for 7 years (113064).
Endocrine ...A case of primary hypothyroidism has been reported for an individual who regularly consumed kratom (27132). However, a causal link between kratom use and thyroid dysfunction has not yet been determined.
Gastrointestinal ...Kratom ingestion has been associated with nausea, vomiting, dry mouth, tongue numbness, increased appetite, and constipation (27130,27136,95797,95818,104637,113067,113080). In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 25% of cases reported gastrointestinal effects (108565). Observational research, data from the British Columbia poison control center, and a report from the US Food and Drug Administration (FDA) Adverse Event Reporting System have found that habitual intake of kratom is associated with withdrawal symptoms, including decreased appetite and diarrhea (27115,113067,113075).
Hepatic
...Orally, kratom has been associated with cases of liver damage.
Between 2003 and 2019, there were 11 cases of liver injury reported in the Drug-Induced Liver Injury Network (DILIN) with definite, highly likely, or probable causality attributed to kratom. Of these cases, 8 were reported between 2017 and 2019. The median time from kratom use to the onset of symptoms was 14 days. Just over half of the patients had evidence of mixed liver injury, including both hepatocellular and cholestatic injury (104634). In addition, published case reports, the FDA adverse event databases, DILIN, and the British Columbia poison control center identified 72 reports of kratom-induced liver injury, although it's possible some duplication of reporting occurred across the databases (103216,113075).
Multiple detailed case reports of liver injury have been published (27133,95798,101703,108761,108764,113075,113076,113084). One case of intrahepatic cholestasis has been reported for a 25-year-old healthy male who consumed kratom powder, starting at 1-2 teaspoons (2.3-7 grams) daily and increasing to 4-6 teaspoons (9-21 grams) daily over 2 weeks (27133). In another case report, a 40-year-old female presented with symptoms of mixed cholestatic and hepatocellular liver injury after consuming kratom once weekly for the past month. Her symptoms resolved upon discontinuation of kratom (101703). Cases of transaminitis, with or without bilirubin elevation, also have been described (95798,108761,113084,113080,113085). In one such case, a 60-year-old patient presented with elevated transaminases and bilirubin after ingesting kratom one teaspoon three times daily for one month. The liver enzymes normalized after discontinuing kratom and receiving supportive treatment with N-acetylcysteine (95798). In another case, a patient with a several-year history of kratom use and a history of hepatic steatosis, choledocholithiasis, and cholecystectomy presented with worsening jaundice, scleral icterus, ascites, and pitting edema. The patient was found to have cholestatic hepatitis consistent with drug-induced liver injury, as well as steatohepatitis with marked fibrosis and scarring (108764). A third case also reported a mixed cholestatic and hepatocellular liver injury in a 23-year-old male who had consumed a cocktail containing kratom leaves, caffeinated soda, and diphenhydramine syrup daily for 2 weeks. Liver function tests normalized after supportive care and discontinuation of the kratom-containing product (113084). In one case of chronic kratom abuse, an adult presented with acute liver failure with hyperbilirubinemia and acute kidney injury. The patient recovered after plasma exchange treatment daily for 4 days in addition to supportive care (114574).
Musculoskeletal
...Observational research has found that habitual intake of kratom is associated with withdrawal symptoms, including arthralgias, lower extremity hyperreflexia, muscle pain, rigidity, spasms, and tremors (27115,27130,104637,113061,113080).
In a case report, a 45-year-old adult who had used kratom intermittently for 10 months experienced mild rhabdomyolysis and generalized seizures (95798). Several cases of severe rhabdomyolysis and associated kidney injury necessitating hemodialysis have been described (108763,108765).
In another case report, a 39-year-old adult experienced transient paralysis, with full awareness but an inability to move or speak, within 1 hour of using kratom. The patient reported a recent history of kratom use over the past few months, but that the paralysis occurred immediately after the use of a different kratom product (108767).
Neurologic/CNS
...In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 75% of cases reported neurologic effects, including agitation, coma, confusion, dizziness, drowsiness, hallucinations, seizures, and tremor (108565).
Other reports of calls to poison control centers related to kratom use and data from the US Food and Drug Administration (FDA) Adverse Events Reporting System show that 5% to 25% of cases included reports of seizures, coma, headache, or confusion (95798,101707,104637,113071).
Multiple cases of kratom-induced new-onset or recurrent generalized tonic-clonic seizures have been reported in regular users of kratom (103214,108760,113069). One case series describes two patients with prior epilepsy who developed breakthrough seizures associated with kratom use and one patient who developed a diagnosis of epilepsy after continued use of kratom. Seizures generally occurred within 1 month of initiation of kratom and ceased with discontinuation of kratom and continuation of an effective antiepileptic drug regimen (108758).
Most case reports of seizure often involve use of multiple active agents, including diphenhydramine, methamphetamine, and other medications not normally associated with seizures (108760). A case of seizure and coma has been reported for a 64-year-old habitual kratom user who had ingested a tea containing an undetermined quantity of kratom and jimson weed 30 minutes prior to the event. This patient had also been taking amitriptyline and oxycodone chronically, although neither of these drugs is typically associated with increased seizure risk (27131). Additionally, a case of generalized tonic-clonic seizures has been reported for a 43-year-old male patient who added modafinil 100 mg to his chronic ingestion of kratom tea four times daily as self-treatment for opioid withdrawal. Modafinil is not generally associated with increased seizures; however, it is speculated that the combination of modafinil with kratom may have contributed to the adverse event (27127). Finally, there is a case report of a 22-year-old male who presented to the emergency room with severe headache, confusion, hypertension, and visual disturbances due to posterior reversible encephalopathy syndrome (PRES) after taking an undisclosed amount of dextroamphetamine and kratom. It is believed that the combination with kratom resulted in increased blood pressure and neurotoxicity that caused PRES (95797).
Orally, kratom has been linked to respiratory depression, particularly when used in combination with other mu-opioid agonists (27119,27120,27136,104637,113075,114755). In reviews of kratom-associated adverse events reported to the National Poison Data System, up to 12% of cases experienced respiratory effects, including respiratory depression (101707,104637,108565). There were 9 reports of deaths most likely due to respiratory depression in patients who ingested a combination product (Krypton) containing kratom and O-desmethyltramadol, another mu-receptor agonist (27119,27120). Serum concentrations of O-desmethyltramadol ranged from 0.4 to 4.3 mcg/gram. Tramadol concentrations >1 mcg/gram are considered toxic, and O-desmethyltramadol is considered to be a more potent metabolite of tramadol. Therefore, it is believed that O-desmethyltramadol probably contributed to the toxicity, but kratom possibly had an additive effect. Nearly all of these patients had brain edema and lung edema or congestion and some also had liver steatosis during autopsy. Many of these patients had a history of drug abuse and also had detectable serum concentrations of antidepressants, benzodiazepines, alcohol, amphetamines, zopiclone, alimemazine, or other drugs (27120).
Kratom was implicated in a case of serotonin syndrome in a patient taking multiple serotonergic prescription medications. In the case report, a 63-year-old male was stable for 2 years on bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone when he started taking kratom 3 times daily for 3 months. The patient presented with aphasia, spontaneous clonus, confusion, diaphoresis, dysarthria, facial droop, fever, flushing, hyperreflexia, and tremors with elevated creatine phosphokinase and lactic acid. Symptoms improved after discontinuing kratom and supportive care with cyproheptadine, lorazepam, intravenous fluids, and cooling blankets (113059).
Observational research has found that habitual intake of kratom is associated with withdrawal symptoms, including hot flashes and fever (27115).
Ocular/Otic ...In patients who habitually ingest kratom, withdrawal symptoms include watery eyes (27115). Additionally, there are multiple case reports of ocular clonus resulting from taking high doses of kratom that users referred to as "the wobbles" (113080).
Psychiatric
...Orally, kratom has been associated with aggression, agitation, altered mental status, anxiety, depression, insomnia, irritability, restlessness, sedation, suicidal ideation, hallucinations, and delusions in case reports and case series (27136,95798,113067,113071,113079,113080,114755).
In a review of kratom-associated adverse events reported to the National Poison Data System, 18.6% of users reported agitation, 13.6% reported drowsiness, 8.1% reported confusion, and 4.8% reported hallucinations (101707). In an analysis of kratom abuse cases in Thailand and the United States from 2010-2017, agitation/irritability, drowsiness/lethargy, confusion, and hallucinations were reported in approximately 26%, 21%, 16%, and 7%, respectively (104637). Additionally, data from the US Food and Drug Administration (FDA) Adverse Event Reporting System from 2004 to 2021 shows that kratom use was linked to dependence, anxiety, withdrawal syndrome, and drug abuse in 11%, 6%, 5%, and 5% of total adverse events reported (113067).
Multiple case reports of patients who habitually ingest kratom at high doses report physical tolerance, dependence, and subsequent withdrawal upon discontinuation that is consistent with DSM-5 diagnostic criteria for kratom use disorder. Some cases of dependence and/or withdrawal have been successfully treated with buprenorphine/naloxone (108757,108766,113061,113079,113080). One case of acute withdrawal symptoms was managed with intravenous lorazepam and dexmedetomidine (114754).
There have been multiple case reports of neonatal abstinence syndrome (NAS) occurring in the infants of patients who used kratom throughout pregnancy. Daily kratom doses in these cases ranged from 15-60 grams daily; self-directed attempts to discontinue use during pregnancy failed due to symptoms of withdrawal. The affected infants were successfully treated with standard NAS monitoring and care (100503,100504). The absence of kratom identification by standard urine toxicology tests can make detection of kratom use challenging (100504,100505). However, specialized umbilical cord testing can identify kratom analytes mitragynine and speciociliatine as biomarkers for in-utero kratom exposure (113062). In some patients, prenatal screening with questionnaires specifically inquiring about kratom use has led to early detection and successful transition to buprenorphine for the remainder of the pregnancy (100505).
Pulmonary/Respiratory ...Orally, kratom has been linked to respiratory depression, particularly when used in combination with other mu-opioid agonists (27119,27120,27136,104637,108565,113071,114755). In one case report, a 36-year-old male with a history of substance abuse and smoking was diagnosed with kratom-induced acute respiratory distress syndrome (ARDS) after presenting with progressive respiratory failure, hypoxemia, and bilateral lung infiltrates. The patient was treated with mechanical ventilation, intravenous methylprednisolone, and supplemental oxygen (113057). Additionally, a 32-year-old male with a history of substance abuse, depression, and obesity presented after collapsing due to seizure with acute mitragynine intoxication. The patient was found to have pulmonary edema along with cardiomegaly with left ventricular hypertrophy, hepatomegaly, and cerebral edema. Postmortem toxicology analysis of blood, organs, and gastric contents were negative for all illicit and prescription drugs except for the kratom components mitragynine and 7-hydroxymitragynine (113069).
Renal
...Orally, kratom has been associated with frequent urination, electrolyte abnormalities, and renal insufficiency, (27130,27136,95797,108762,113066,113068).
In one case report, a 61-year-old male with no significant past medical history experienced persistent asymptomatic hyperkalemia after 4 months of regular, nearly daily use of kratom. Potassium levels normalized upon discontinuation of kratom (108762). In another case, a 62-year-old male with severe hyponatremia presented with altered mental status, restlessness, and minimal fluid intake after consuming large doses of kratom. The hyponatremia was treated with fluids and discontinuation of kratom (113068).
In another case report, a 21-year-old female was diagnosed with acute renal insufficiency after presenting with nausea, vomiting, left flank pain, elevated serum creatinine, proteinuria, and bilateral enlarged kidneys after consuming kratom tea. Testing of the kratom leaf sample revealed the presence of hydrocodone, morphine, and mitragynine which all contributed to acute renal insufficiency. The symptoms resolved following discontinuation of the kratom product and supportive care with intravenous fluids. It is unclear whether the renal insufficiency was due to kratom or the other adulterants in the tested sample (113066).
Other
...Data from the US Food and Drug Administration (FDA) Adverse Event Reporting System shows that from 2004 to 2021, out of 489 kratom-related adverse reaction reports, 102 deaths and 34 accidental deaths were reported, accounting for 21% and 7% of total adverse events reported.
However, only 45% of reported adverse events listed kratom as the only drug ingested (113067). In February 2018, the FDA reported at least 44 deaths associated with kratom use. This number was based on information from academic research, poison control centers, medical examiner reports, social science research, and adverse event reports. The exact cause of death was not determined in most cases (95804). More recently, the Centers for Disease Control and Prevention (CDC) analyzed data from the State Unintentional Drug Overdose Reporting System (SUDORS) to determine what percentage of kratom-positive deaths reported between July 2016 and December 2017 were caused by kratom. Of 27,338 overdose deaths reported, 152 of the decedents tested positive for kratom in a postmortem analysis. Of these cases in which the decedents were kratom-positive, 91 of the deaths were considered to be kratom-involved (99182). In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 8 deaths occurred in cases where kratom was the only substance involved (108565). Adverse effects prior to kratom-related death have included pulmonary edema and congestion, pulmonary embolism, encephalopathy, cardiorespiratory arrest, cardiomegaly, hemorrhagic stroke, and seizures (95804,113069).
In almost all cases, kratom was used along with other drugs, so it is unclear if kratom was the primary causal agent or a contributing factor (95804,99182,99811,103217,113067). Furthermore, in an analysis of deaths attributed to kratom in Colorado, re-testing of residual blood from decedents found that all cases of kratom-related death involved other drugs, including those that were initially reported as not involving other drugs (99811). Concomitant drugs included fentanyl, benzodiazepines, opioids, stimulants, antidepressants, antihistamines, antitussives, sedatives, antihypertensives, antidiarrheals, anticonvulsants, and other medications (95804,99182,99811). Additionally, samples of commercially available kratom products may contain high levels of lead which pose significant health risks to consumers, especially at high doses. There is significant overlap in adverse effects in the central nervous system, liver, gastrointestinal tract, and cardiovascular system between kratom and lead toxicity, which raises the possibility that toxic effects attributed to kratom may actually be due to lead contaminants in kratom products (113074).
Long-term, heavy kratom intake does not appear to be associated with abnormalities in standard hematological and clinical chemistry blood tests (98450,98451).
General ...Orally or by inhalation, Salvia divinorum can cause hallucinogenic effects. These include restlessness, hyperactivity, disorientation, loss of coordination, dizziness, slurred speech, altered perceptions, changes in perception of body temperature, personal detachment or distorted body ownership, fatigue, severe mood changes, and psychosis. Most of these effects resolve within 20 minutes; however, some effects might last longer (7350,7351,15820,72901,100001,100002).
Gastrointestinal ...Orally, Salvia divinorum can cause nausea (7350).
Neurologic/CNS ...Neurologic changes caused by Salvia divinorum are rapid, intense, and short-lived. Most evidence suggests a peak effect within 2 minutes following consumption by smoking, with a slower peak when consumed orally. Most symptoms cease within 20 minutes; however, the 'high' can last as long as 2 hours. Symptoms include headache, restlessness, hyperactivity, disorientation, loss of coordination, dizziness, slurred speech, altered perceptions, including auditory, visual, tactile, and kinesthetic hallucinations, a feeling of being pinned to the floor, changes in perception of body temperature, personal detachment or distorted body ownership, and fatigue. These effects are not sustained and follow-up assessments weeks later usually show no lasting negative effects (7350,7351,15820,100001,100002).
Psychiatric ...Psychiatric changes caused by Salvia divinorum are rapid, intense, and short-lived. Most evidence suggests a peak effect within 2 minutes following consumption by smoking, with a slower peak when consumed orally. Most symptoms cease within 20 minutes; however, the 'high' can last as long as 2 hours. Symptoms include disturbed reality and mood changes including both euphoria or extreme happiness and severe anxiety, fear, or panic (72901,100001,100002). Rarely, the use of Salvia divinorum has been associated with both acute and chronic psychotic episodes. Whether Salvia divinorum use was directly responsible for these episodes is not yet clear. Some individuals were using cannabis or other recreational drugs concurrently and/or were possibly at increased risk of schizophrenia. However, these risk factors were not consistent, and the episodes occurred following the use of Salvia divinorum in all cases (100002). Salvia divinorum appears to have a low potential for abuse (100001).
