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Khat (Catha edulis)

catha_edulisCatha edulis is Uncontrolled in the United States, however, it is not approved for human consumption. It is a gray area of the law because the it contains, cathinone, which is a Schedule I chemical.

Addictive Potential: Low

Emergency Room Visits Yearly: Unkown

Mandatory Minimum Sentence: Unknown

Mechanism of Action: increases dopamine and noradrenalin

Overview:

Khat (Catha edulis) also known as qat, qaat, quat, gat, jaad, chat, chad, chaad and miraa, is a flowering plant native to tropical East Africa and the Arabian Peninsula. It has been reported that, when the plant’s leaves are chewed, it produces a stimulant and euphoric effect.

Khat contains more than 40 alkaloids, glycosides, tannins, amino acids, vitamins and minerals. Most of the effect of chewing khat is thought to come from two phenylalkylamines – cathinone and cathine – which are structurally related to amphetamine. The presence of amphetamine and caffeine in khat has been excluded. A number of other constituents, including cathidine, eduline and ephedrine, have been identified, but it is unlikely that any of these, except tannin, play a role in khat’s effects.

Cathinone has been termed a ‘natural amphetamine’. It produces sympathomimetic and central nervous system stimulation analogous to the effects of amphetamine, hence its similar clinical effects. The difference in effect is due to slight pharmacodynamic variations between the stimulating substances, to other plant constituents (mainly tannins), and to differences in dosage and the mode of consumption.

Cathinone is also named (–)-alpha-aminopropiophenone. It is considered to be the most active ingredient of khat. It has been isolated and synthesized and its effects have been shown to be similar to amphetamine, but with a lower potency. Cathinone is estimated to be 7–10 times more potent than cathine. It is difficult to synthesize, therefore it is unsuitable for marketing as a pure substance for drug misuse.

Cathine is also named (+)-norpseudoephedrine and phenylpropanolamine. It had previously been isolated from the plant ephedra, which has effects similar to those of khat. Cathine has a milder psychostimulant action than cathinone and the effects last for only a short time, so the user must chew leaves almost continuously. It plays only a minor role in the action of khat, but it is cathine that is responsible for the unwanted systemic effects. Normally, fresh leaves contain a higher proportion of the desirable cathinone. Where the content of cathine is relatively higher, the cathine causes more unwanted systemic effects. On drying, cathinone breaks down into cathine. Therefore khat chewers prefer fresh leaves that contain a higher proportion of cathinone to cathine, so that they obtain a better stimulation with fewer systemic adverse effects.

The constituents of khat have been shown to exert their effects on two main neurochemical pathways: dopamine and noradrenalin. It has also been postulated that, like amphetamine, cathinone releases serotonin in the central nervous system. Both cathinone and amphetamine induce release of dopamine from central nervous system dopamine terminals and thus increase the activity of the dopaminergic pathways. Cathinone has a releasing effect on noradrenalin storage sites, which supports the conclusion that cathinone facilitates noradrenalin transmission. Drake (1988) also proposed that cathinone and cathine cause inhibition of noradrenalin uptake.

The euphoric effect appears shortly after the chewing begins, suggesting absorption from the oral mucosa. The effect of cathinone is maximum after 15–30 minutes. Metabolism of cathinone is rapid, occurring mainly during first passage through the liver. Only a small fraction (about 2%) appears unchanged in the urine. Most cathinone is metabolized to norephedrine and is excreted in this form. The rate of inactivation is about the same as the rate of absorption, which limits the cathinone blood levels attainable by chewing. Cathine has a slower onset of action, with a serum half-life in humans of about 3 hours. It is excreted unchanged in the urine within about 24 hours. When taking khat, large amounts of non-alcoholic drinks are consumed. There is pharmacological synergism with drinks containing methylxanthines (e.g. tea and cola), which therefore enhances the effects of khat.

Side Effects and Adverse Reactions:

Khat (Catha edulis) use may produce dependence, similar to other stimulants. Khat can interact with therapeutic drugs. Phenylpropanolamine, which can display synergism with khat, is widely available in over-the-counter cold and appetite-suppressant preparations and in prescription drugs. The use of monoamine oxidase inhibitors is to be avoided in khat users, as this is likely to precipitate a dangerous level of sympathetic stimulation, possibly leading to a hypertensive crisis.

Research:

Cathine, an amphetamine-related compound, acts on mammalian spermatozoa via beta1- and alpha2A-adrenergic receptors in a capacitation state-dependent manner

Biochemical effects of Catha edulis, cathine and cathinone on adrenocortical functions

Adverse effects of khat: a review

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