Khat is a masticatory herb with amphetamine-like sympathomimetic effects. Chronic users often have a staring gaze and brown-stained teeth, but no long-term harmful effects have been clearly shown. Occasional cases of psychosis have been reported.

[LFODPKM ] Letter Key

Latin Name

Catha edulis (Vahl) Forssk. Ex Endl.

Family

Celastraceae

Other Common Names

Abbyssinian tea, qat, kaht, kat, gad, tschat, chat, jaad, and miraa (Kenya)

Description

• A small evergreen tree that grows at high altitudes, khat is cultivated in Ethiopia, east and south Africa, and Yemen.
• Khat use is very widespread in Yemen but it is also used commonly in Ethiopia, Kenya, and Djibouti (1).

Part Used

Fresh leaves

Known Active Constituents

• Khat contains sympathomimetic alkaloids including cathine [norpseudoephedrine, or S,S (+)-phenylproponolamine], its diasteromer norephedrine [R,S (—)-phenylpropanolamine], and cathinone [S(—) alpha-amino prophenone, a keto analog of cathine]. Cathinone is most concentrated in young leaves, where it may compose 70% of the phenylalkylamine fraction (2).
• The alkaloid content of khat varies; 100 g of fresh khat may contain 36 mg cathinone, 120 mg cathine, and 8 mg norephedrine. Young fresh leaves are highest in cathinone.

Mechanism/Pharmacokinetics

• Cathinone is substantially absorbed through the buccal mucosa. After oral administration in capsules, peak serum levels of cathinone are reached within an hour; it is converted to norephedrine and disappears from serum within 6 hours (3).
• Orally administered cathinone is similar to amphetamine but has a more rapid onset of action (3). In six khat-naïve volunteers who received a single oral dose of khat corresponding to 0.8 mg/kg body weight, maximal plasma levels of cathinone were attained within 30 minutes and the elimination half-life was 260 ± 102 minutes (4). An earlier experiment found similar effects of pure cathinone (0.8 mg/kg body weight); the main difference was that, compared with taking pure cathinone, chewing the leaf slowed the absorption of cathinone and caused a later plasma peak. Khat significantly prolonged gastric emptying in a controlled study in 12 healthy volunteers (5).
• Cathinone, although more potent that cathine, is quite unstable, dimerizing spontaneously to an inactive compound (6). Cathine is absorbed slowly from the gastrointestinal tract; little is absorbed through the buccal mucosa.

[Outline]

• LLatin Name
• FFamily
• OOther Common Names
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CAO ] Letter Key

Clinical Trials

• No clinical studies of benefit were identified. Clinical studies of adverse effects have been performed (see risks).

Animal/In Vitro

• In animals, khat alkaloids have sympathomimetic effects, can induce an indirect analgesic effect apparently secondary to its central nervous system stimulating effect, and can cause hyperthermia (3). Anorexic effects are also noted, although this effect is less potent than with amphetamine, and tolerance to the weight-reducing effect disappears more quickly than amphetamine—within a month.
• Cathinone induces locomotor activity, an effect that can be prevented by pretreatment with dopamine antagonists. Cathinone also increases the sensitivity of test animals to external stimulation (3).

Other Claimed Benefits/Actions

• Asthma
• Ulcers
• Reducing fatigue

[Outline]

• CClinical Trials
• AAnimal/In Vitro
• OOther Claimed Benefits/Actions

[ADPT ] Letter Key

Adverse Reactions

• Male reproductive tract effects
  • Long-term use of khat may cause erectile dysfunction (3). A comparison of 65 khat addicts and 50 non-khat addicts found that semen volume, sperm count, sperm motility, motility index, and percentage of normal spermatozoa were lower among khat addicts (7). Among khat addicts, a mean of 65% of sperm were deformed.
• Memory
  • A comparative study among flight attendants presenting for Federal Aviation Administration medical examinations compared 25 daily khat-chewing flight attendants with 39 occasional khat-chewing flight attendants and 24 air crew members who did not chew khat (8). Memory function test scores were significantly lower in khat chewers, and the effect was more pronounced in regular khat chewers than social khat chewers. Regular chewers also experienced a statistically significant shift toward fast frequency bands in electroencephalograms; however, this did not correlate with the memory functions assessed.
• Urodynamics
  • A randomized double-blind controlled trial in 11 healthy males tested the results of a khat-chewing session preceded by placebo or indoramin. Khat chewing decreased average and maximum urine flow rates. This effect was inhibited by indoramin, causing the researchers to conclude that urinary side effects may be mediated by stimulation of ₁-adrenergic receptors (9).
• Psychosis
  • Khat-related psychosis is well-documented but reports are relatively rare. Khat may cause hypomania or mania, often with grandiose delusions, or a paranoid psychosis often associated with fear, anxiety and possibly auditory hallucinations (10). Phenothiazines have been used to treat khat-induced psychosis (3).
• Immediate and chronic effects of khat use
  • Immediate effects of khat use include transient conjunctival and facial congestion, tachycardia, palpitations (sometimes with extrasystole), increased blood pressure, mydriasis, hyperthermia, sweating, increased respiratory rate, and anorexia. Changes in heart rate and blood pressure are more pronounced among naïve users than chronic users.
  • Khat users experience moderate euphoria, increased energy, volubility, a labile affect, and other symptoms consistent with mild hypomania. Khat-naïve participants given a single dose of khat (0.8 mg/kg body weight) were evaluated with the Addiction Research Center Inventory Scale. Khat had a significant amphetamine-like effect and caused participants to feel more excited and energetic (4).
  • A staring gaze, dilated pupils and brown staining of the teeth are common in heavy khat users. It is unclear whether khat consumption affects periodontal health; however, stomatitis with secondary infections are commonly seen among khat users (3). A survey of 706 Yemenis (638 khat users and 168 non-khat users) that included a history and physical found that the only adverse effects clearly linked to the level of khat consumption were gastrointestinal problems and insomnia (10).
• Dependence/withdrawal
  • Although psychic dependence is common, physical dependence does not seem to occur. Tolerance to mood-elevating effects does not appear to occur, although chronic users may cease to experience insomnia, and effects on heart rate and blood pressure are less pronounced in chronic users (3). Discontinuation of khat after heavy use may cause slight trembling, lassitude, mild depression, increased desire for sleep, and nightmares that may have paranoid content (11). Two cases of khat addiction were successfully treated with bromocriptine (12).

Drug Interactions

• General anesthesia
  • A French report from 1969 noted that khat users are more likely to become psychotic in the postanesthetic phase (1).
• Amoxicillin and ampicillin
  • A bioavailability study on 8 healthy males tested the effect of khat chewing on ampicillin and amoxicillin bioavailability. Each antibiotic was tested under fasting conditions, taken right before khat chewing, taken before khat chewing together with food and drinks, taken 2 hours before khat chewing, taken midway through a 4-hour khat-chewing session, and taken 2 hours after that khat-chewing session. Both the extent and the rate of ampicillin bioavailability were substantially reduced by chewing khat at all timepoints tested except when the antibiotic was taken 2 hours after chewing khat. The strongest effect was seen if the drug was administered during a khat-chewing session (13). In contrast, amoxicillin bioavailability was reduced only if the antibiotic was taken during a khat-chewing session.

Pregnancy/Lactation

• A study of 1,141 consecutive deliveries in the Yemen Arab Republic found that nonusers of khat (n = 427) had significantly fewer low birth weight babies than khat users (223 occasional users and 391 regular users) (14). There were no differences between groups in rates of stillbirths or congenital malformations.
• Nor-pseudoephedrine has been found to be excreted in breast milk in several lactating, khat-chewing women (15). Norpseudoephedrine was also seen in the urine of one infant.

Animal Toxicity

• Cathinone is less averse than amphetamine in conditioning studies; it causes higher levels of response and tolerance to its anorectic effect is more rapid than amphetamine (1).
• Khat reduces the fertility of female mice and rats and appears to reduce placental blood flow and impair fetal growth in guinea pigs.

[Outline]

• AAdverse Reactions
  • Male reproductive tract effects
  • Memory
  • Urodynamics
  • Psychosis
  • Immediate and chronic effects of khat use
  • Dependence/withdrawal
• DDrug Interactions
  • General anesthesia
  • Amoxicillin and ampicillin
• PPregnancy/Lactation
• TAnimal Toxicity

Common Dosage Forms

• Fresh, preferably young, leaves are chewed one at a time. The juice is swallowed and the residue expelled.

• Doesn’t khat increase the risk of oral cancers?
• Is khat used medicinally?
• What happens during a khat-chewing session?
• What is the economic impact of khat?

Q: Doesn’t khat increase the risk of oral cancers?

A: There is no convincing evidence of that. A survey of 706 Yemenis (638 khat users and 168 non-khat users) included oral examinations; no oral cancers were found (10). A 2-year record review of oral, oropharyngeal, and other head and neck malignancies in the Asir region of Saudi Arabia found that 10 of 28 were nonsmoking long-term khat-chewers (16). However, this study is unconvincing, not only because of its small size, but also because it is not at all clear that the prevalence of use was any higher than in the general population.

Q: Is khat used medicinally?

A: Although the use of khat is at least seven centuries old (its use was recommended to combat hunger and fatigue in messengers and soldiers) and it is a home remedy for asthma, khat does not appear to be a traditional remedy of Yemen.

Q: What happens during a khat-chewing session?

A: Khat chewing is often a social event; users usually bring their own leaves, which are chewed one at a time. The juice is swallowed, and the residue stored in the cheek and expelled at the end of the session. A khat-chewing session may last 4 hours, with each consumer consuming 100 to 200 g of leaves. In Yemen, khat chewing is primarily a male habit. In Somalia, women (either in female or mixed groups) regularly consume khat; chewing sessions often include consumption of copious amounts of highly sweetened tea or Coca-Cola.

Q: What is the economic impact of khat?

A: Khat use has a major economic impact. In Yemen, poor families spend up to half of their income on khat. It is estimated that over 40% of irrigated farmland is used for khat cultivation (far more than is used for cereal farming or coffee) (17).

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