Khat Toxicity

Khat (Catha edulis, also called miraa, qat or mairungi) is a shrub whose fresh leaves and twigs are chewed for a stimulant effect. About 20 million people use it, mainly in East Africa (Kenya, Ethiopia, Somalia, Djibouti) and the Arabian Peninsula, and it is used in diaspora communities. Most users are young men, and use is common in social settings.

The active compounds are cathinone (fragile, present only in fresh leaves) and its less active metabolites cathine and norephedrine. Cathinone releases noradrenaline, dopamine and serotonin, and blocks their reuptake, a mechanism like amphetamine. A session of 100 to 200 g of fresh leaves delivers about 50 to 100 mg of cathinone over 3 to 6 hours. Cathinone degrades within 48 hours of picking, so leaves are transported fresh. Synthetic cathinones (mephedrone, methylone, "bath salts") are far more potent and cause more severe toxicity.

Acute effects are euphoria, alertness, talkativeness, reduced appetite and sleep. Toxicity follows heavy or prolonged use.

Chronic use is associated with

• Cardiovascular disease: hypertension, myocardial infarction, cardiomyopathy and stroke
• Psychiatric illness: insomnia, mania, paranoid psychosis (2 to 4 times the baseline risk) and depression
• Gastrointestinal and oral disease: gastritis, constipation, hemorrhoids, dental caries and oral keratosis
• Reduced birth weight in pregnancy, and sexual dysfunction
• Dependence, with mild withdrawal

Psychosis usually settles within days to 2 weeks after stopping.

• Acute: dilated pupils, tachycardia, raised blood pressure, sweating, hyperthermia, bruxism, dry mouth, tremor, restlessness and insomnia
• Toxic: agitation, paranoia, visual or auditory hallucinations, chest pain, arrhythmia and seizures
• Chronic: weight loss, constipation, hemorrhoids, tooth loss and a stained, ulcerated oral mucosa
• Withdrawal (1 to 3 days): lethargy, low mood, irritability, nightmares and mild tremor
• Pregnancy: low birth weight and reduced breast milk
• Red flags: chest pain, temperature over 39 degrees Celsius, blood pressure over 180/110 mmHg, first-episode psychosis, and use with other drugs

1. History and examination: quantity, duration and timing of khat use, other drugs, vital signs, temperature and mental state.
2. ECG, troponin, creatine kinase, electrolytes, creatinine and glucose for chest pain, agitation or hyperthermia.
3. Urine toxicology: routine amphetamine immunoassays often miss cathinone and cathine. Confirm by mass spectrometry for cathinone, cathine and norephedrine when it matters.
4. CT head for focal neurological signs, or a severe sudden headache.
5. Thyroid function and a psychiatric assessment for first-episode psychosis.

Differentials, in order of exclusion: amphetamine, cocaine and synthetic cathinone toxicity, serotonin syndrome, thyrotoxicosis, alcohol withdrawal, primary psychotic or bipolar disorder, anticholinergic poisoning.

1. Mild toxicity: calm environment, oral fluids, observation for 4 to 6 hours.
2. Agitation: lorazepam 1 to 2 mg orally or IV (children 0.05 mg/kg) every 10 to 15 minutes, or diazepam 5 to 10 mg IV (children 0.1 to 0.2 mg/kg), titrated to calm. Monitor respiration. Avoid oversedation.
3. Psychosis persisting after benzodiazepines: olanzapine 5 to 10 mg orally or IM once (maximum 20 mg in 24 hours, avoid IM olanzapine within 1 hour of a parenteral benzodiazepine), or haloperidol 2.5 to 5 mg IM (check QTc, avoid when over 500 ms). For psychosis lasting beyond 3 days give risperidone 1 to 2 mg orally once daily for 2 to 4 weeks, then stop.
4. Hypertension: treat with benzodiazepines first. For severe hypertension with end-organ effects use glyceryl trinitrate 5 to 200 micrograms/min IV or phentolamine 1 to 5 mg IV. Avoid beta blockers alone.
5. Chest pain or suspected infarction: aspirin 300 mg chewed once, glyceryl trinitrate 0.4 mg sublingually every 5 minutes up to 3 doses, and the acute coronary syndrome pathway.
6. Hyperthermia over 39 degrees Celsius: external cooling and IV 0.9% saline 20 mL/kg.
7. Rhabdomyolysis: IV 0.9% saline 200 to 300 mL/h to keep urine output over 1 mL/kg/h, with potassium monitoring.
8. Gastrointestinal and dental care: omeprazole 20 mg orally daily for 4 to 8 weeks, macrogol 3350 17 g orally daily for constipation, and dental referral.
9. Cessation: brief motivational intervention, sleep hygiene and screening for depression. No licensed drug exists for dependence. Withdrawal is managed supportively.
10. Pregnancy: advise stopping, and monitor fetal growth.

Follow-up at 2 weeks for blood pressure and psychosis, then at 3 months. Counsel on cardiovascular risk and on avoiding combining khat with alcohol or other stimulants.