Khat

or qat, is a stimulant commonly used in East Africa, Yemen, and Southern Saudi Arabia. Khat leaves from the evergreen bush Catha edulis are typically chewed while fresh, but can also be smoked, brewed in tea, or sprinkled on food. Its use is culturally based. 

The major effects of khat on the central nervous system can be attributed to cathinone (S-(-)-alpha-aminopro-priophenone) in fresh khat leaves and cathine (norpseu-doephedrine) in dried khat leaves and stems. Cathinone, a phenylalkylamine, is the major active component and is structurally similar to amfetamine. It degrades to norp-seudoephedrine and norephedrine within days of leaf picking. Cathinone increases dopamine release and reduces dopamine re-uptake (1). 

Khat has been recognized as a substance of abuse with increasing popularity. It is estimated that 10 million people chew khat worldwide, and it is used by up to 80% of adults in Somalia and Yemen. It now extends to immigrant African communities in the UK and USA. It is banned in Saudi Arabia, Egypt, Morocco, Sudan, and Kuwait. It is also banned in the USA and European countries. However, in Australia, its importation is controlled by a licence issued by the Therapeutic Goods Administration, which allows up to 5 kg of khat per month per individual for personal use. 

There have been several review articles describing khat and its growth. The World Health Organization Advisory Group s 1980 report reviewed the pharmacological effects of khat in animals and humans (2). The societal context of khat use has also been reviewed (3). 

Khat is a sympathomimetic amine and increases blood pressure and heart rate. Limited evidence suggests that khat increases the risk of acute myocardial infarction. In Yemen 100 patients admitted to an intensive care unit with an acute myocardial infarction were compared with 100 sex- and age-matched controls recruited from an ambulatory clinic (4). They completed a questionnaire on personal habits, such as khat use and cigarette 

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Kalix P, Braenden O Pharmacological aspects of the chewing of khat leaves. Pharmacol Rev 37 149-164, 1985... 

Patel NB. Mechanism of action of cathinone the active ingredient of khat (Catha... 

Connor J. D, Ruston A, Eyasu M. Comparison of effects of khat extract and amphetamine on motor behaviors in mice. J Ethnopharmacol 2002 81 65-71. 

Strychnine is a convulsant, used commercially as a rat poison. However, at low doses it can act as a CNS stimulant. Small amounts of strychnine are sometimes present in LSD tablets produced in illicit laboratories. It has been suggested that the degree to which an LSD tablet is alerting may reflect its strychnine content (Chapter 6). Khat... 

Cathinone An amphetamine derivative found in khat extracted from Catha edulis growing in the Horn of Africa, where it is widely used as a recreational stimulant. 

Khat (Qat) The Horn of Africa plant Catha edulis containing the amphetamine-like drugs, cathine and cathinone (norpseudoephedrine). 

Chewing leaves of the khat shrub is practiced in parts of East Africa and the Arabian peninsula (Kalix 1988 Widler et al. 1994). Some estimate daily use at 5 million portions. Use in the West is less common, but has increased somewhat. More common in the United States has been use of the synthetic drug methcathinone (or "cat"), which is derived from khat alkaloids. Only the fresh khat leaves are pharmacologically active, so for some time use was limited to local areas that grew the plant. However, with air transportation, use has spread with emigrants in Europe and the United States. Because of its pharmacological similarities to amphetamine and its addictive properties, khat has been listed on Schedule I of the United Nations Convention on Psychotropic Substances. 

There are more than 40 alkaloids, glycosides, tannins, and terpenoids in khat (Elmi 1983). Two phenylalkylamines, namely, cathine (norpseudoephedrine) and cathinone [S(-)-alpha-aminopropiophenone] well account for the CNS stimulant effects (Kalix 1988) (figure 4.17). The... 

In its natural form, fresh khat leaves are chewed because the drug is perishable. Young leaves from the tip of the branch are more potent. While the leaves are chewed, the juices are swallowed and the residue is rejected. During a session, one may ingest 100 to 200 grams of leaves. 

When khat is chewed, absorption of cathinone is slow, with maximal plasma concentrations occurring at approximately 2 hours (Widler et al. 1994 Halket et al. 1995). The terminal elimination half-life is approximately 4.3 hours. Similar effects are achieved with orally administered pure cathinone. Cathinone is the keto-analog of cathine and because it is more lipophilic it penetrates the blood-brain barrier more easily. 

Khat produces effects similar to those of other monoamine stimulants, (i.e., increases in mental stimulation, physical endurance, elevated mood) (Widler etal. 1994 Kalix 1994 Brenneisen etal. 1990). Stimulus generalization occurs between cathinone, amphetamine, and cocaine, suggesting similar subjective effects (Huang and Wilson 1986). Similar to other monoamine stimulants, cathinone causes dose-dependent reductions in eating and body weight (Islam et al. 1990 Zelger and Carlini 1980). Oral cathinone increases sexual arousal in rats, but does not affect erectile or ejaculatory responses (Taha et al. 1995). 

Khat may cause irritability, but in the cultural context, sociability is generally increased. Users may increase in talkativeness, sometimes to... 

Khat produces sympathomimetic effects, increasing heart rate and blood pressure. When khat is chewed, the increases are gradual, maximizing at about 2 hours and lasting for 4 hours. However, tolerance develops to blood pressure and heart rate effects in habitual users. Mydriasis and increases in respiration also occur. Cathinone induces thermogenesis in brown adipose tissue, which is mediated by jS-adrenergic receptors (Tariq et al. 1989). 

Animals self-administer cathinone in a pattern common to abuses of monoamine stimulants such as cocaine (Woolverton and Johanson 1984). Cathinone can induce a conditioned place preference in rats (Schechter 1991). Withdrawal symptoms of khat include lethargy, depression, nightmares, and mild tremor (Kalix 1994). /V-methylated cathinone (methcathinone) is more potent, and has become available on the illegal market. It was subsequently scheduled as a controlled substance (Glennon et al. 1995). 

Use of cathinone in the form of chewing khat may have some features that limit its addictiveness (Kalix 1994). The large bulk of the material and the effort required to chew khat limits the amount that can be ingested in a given time. Absorption in this manner is slow and gradual. 

As would be expected, khat overuse produces symptoms similar to those of other monoamine stimulants, such as cocaine or amphetamine, including signs of sympathetic overarousal. In the extreme this can involve a toxic psychosis. Disorders more frequently associated with chronic khat use in males are headaches, anorexia, insomnia, constipation, and respiratory illnesses (Kennedy et al. 1983). Females report higher incidences of acute gastritis, jaundice, bronchitis and hepatic diseases. Also, cathinone has toxic reproductive effects in humans and experimental animals (Islam et al. 1990). It decreases sperm count and motility, and increases the number of abnormal sperm cells. It also decreases plasma testosterone in rats. 

Brenneisen R, Fisch FiU, Koeibing U, Geisshtisier S, Kaiix P. (1990). Amphetamine-like effects in humans of the khat aikaioid cathinone. BrJ Clin Pharmacol. 30(6) 825-28. 

Granek M, Shalev A, Weingarten AM. (1988). Khat-induced hypnagogic hallucinations. Acta Psychiatr Scand. 78(4) 458-61. 

Halket JM, Karasu Z, Murray-Lyon IM. (1995). Plasma cathinone levels following chewing khat leaves (Catha edulis Forsk.). J Ethnopharmacol. 49(2) 111-13. 

Kalix P. (1980). A constituent of khat leaves with amphetamine-like releasing properties. EurJ Pharmacol. 68(2) 213-15. 

Kalix P. (1981). Cathinone, an alkaloid from khat leaves with an amphetamine-like releasing effect. Psychopharmacology (Berlin). 74(3) 269-70. 

Kalix P. (1982). The amphetamine-like releasing effect of the alkaloid (-)cathinone on rat nucleus accumbens and rabbit caudate nucleus. Prog Neuropsychopharmacol Biol Psychiatry. 6(1) 43-49. Kalix P. (1983). A comparison of the catecholamine releasing effect of the khat alkaloids (-)-cathinone and (+)-norpseudoephedrine. Drug Alcohol Depend. 11(3-4) 395-401. 

Kalix P. (1988). Khat a plant with amphetamine effects. J Subst Abuse Treat. 5(3) 163-69. 

Kalix P. (1994). Khat, an amphetamine-like stimulant. Psychoactive Drugs. 26(1) 69-74. 

Mereu GP, Pacitti C, Argiolas A. (1983). Effect of (-)-cathinone, a khat leaf constituent, on dopaminergic firing and dopamine metabolism in the rat brain. Life Sci. 32(12) 1383-89. 

Nencini P, Amiconi G, Befani 0, Abdullahi MA, Anania MC. (1984). Possible involvement of amine oxidase inhibition in the sympathetic activation induced by khat (Catha edulis) chewing in humans. J Ethnopharmacol. 11 179-86. 

Taha SA, Ageel AM, Islam MW, GInawl OT. (1995). Effect of (-)-cathinone, a psychoactive alkaloid from khat (Catha edulis Forsk.) and caffeine on sexual behaviour in rats. Pharmacol Res. 31(5) 299-303. 

Wilder P, Mathys K, Brenneisen R, Kalix P, Fisch HU. (1994). Pharmacodynamics and pharmacokinetics of khat a controlled study. Clin Pharmacol Ther. 55 556-62. 

Yu G, Maskray V, Jackson SH, Swift CG, Tiplady B. (1991). A comparison of the central nervous system effects of caffeine and theophylline in elderly subjects. BrJ Clin Pharmacol. 32(3) 341-45. Zelger JL, Carlini EA. (1980). Anorexigenic effects of two amines obtained from Catha edulis Forsk. (Khat) in rats. Pharmacol Biochem Behav. 12(5) 701-5. 

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