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Books - The health and socio-economic aspects of Khat use
Written by P. Kalix   


The chewing of fresh leaves of the khat shrub is common in certain countries of East Africa and the Arab Peninsula and the habit causes social and public health problems among the populations concerned. The tendency of many khat users to obtain their daily supply by any means is a clear manifestation of psychic dependence. The pleasurable effect that is induced by khat chewing is a moderate degree of central stimulation with ensuing elation and removal of tiredness. Since khat also has a pronounced anorectic effect, it is an attractive aid for alleviating the sensations of hunger and fatigue. Furthermore, the leaves cause hyperthermia and peripheral symptoms such as mydriasis, arrhythmias and sometimes, hypertension. Thus, the syndrome that is observed after khat consumption is reminiscent of that brought about by amphetamine (1).
Recently, the phenylethylamine alkaloid (-)cathinone has been isolated from khat leaves. Administration of this substance to animals produces effects that correlate with those seen in humans after khat consumption. (-) Cathinone causes restlessness, hypermotility, anorexia and hyperthermia and among its peripheral effects are mydriasis, hypertension and, in isolated atria, a positive inotropic and chronotopic action (2, 3, 4). Furthermore, it has been shown that monkeys tend to self-administer (-)cathinone at a high rate (2). Therefore, (-)cathinone appears to be the main active principle of khat leaves and, especially, the constituent that induces compulsive khat consumption. Comparison of the hypermotility caused by, respectively, (-)cathinone and (+)amphetamine revealed that the effects of these compounds are pharmacologically analogous and that (-)cathinone has a potency similar to that of (+)amphetamine. The effect of (-)cathinone on the motor activity of mice and its antagonism by neuroleptic compounds is depicted in figures 1 and 2.
Figure 1. The effect of increasing concentrations of (-)cathinone on the motor activity of mice, expressed as locomotor movements ( ) and movements of small amplitude (0 ). The motor activity of saline-injected animals during the same period was 229 + 91 locomotor counts and 209 + 89 counts for movements of small amplitude. For details see reference 5.
Figure 2. The effect of neuroleptic pretreatment on the (-)cathinone-induced locomotor activity of mice. The substances were injected 45 min (pimozide 3hr) prior to administration of 18 mg/ kg (-)cathinone. The shaded area indicates the effect observed without pretreatment, the value corresponds to the maximum appearing in fig. 1; n was 7 for the highest dose of haloperidol and 5 for all other experiments. For details see reference 5.
Figure 3. The effect of (-)cathinone (CATH) and (+)amphetamine (AMPH) on the release of radioactivity from rat nucleus accumbens tissue prelabelled with 3H-dopamine. The efflux from an unstimulated control preparation perfused simultaneously is indicated by open triangles. For details see reference 6.
Figure 4. The effect of increasing concentrations of (-)cathinone on the release of radioactivity from rabbit caudate nucleus tissue prelabelled with 3H-dopamine. Each fraction corresponds to 3 min of efflux, for details see reference 7.
Experiments with isolated tissue from the nucleus accumbens, a brain area supposed to mediate amphetamine hypermotility, demonstrated that the two amines have a releasing effect on physiological catecholamine storage sites: as (+)amphetamine, (-)cathinone was found capable of enhancing the efflux of radioactivity from tissue slices that had been prelabelled with 3H-dopamine (figure 3). Similar observations were made on tissue from the caudate nucleus, an organ thought to be responsible for the stereotypical movements induced by amphetamine-like compounds (figure 4). Furthermore, it was investigated if the releasing effect of (-)cathinone observed in the CNS pertained also to peripheral tissues. When slices of rabbit heart (atrium) that had been prelabelled with 3H-noradrenaline were superfused with solutions of either (-)cathinone or (+)amphetamine, a rapid increase of efflux of radioactivity was observed, an effect that indicates that the sympathomimetic side effects seen during khat consumption are probably due to release of neurotransmitter at cardio-vascular sites (8).
Thus, it appears that the symptoms produced by khat chewing can be largely accounted for by the effects of the alkaloid (-) cathinone and that this compound is a potent amphetamine-like substance. With regard to the mechanism of action of the alkaloid, the efflux experiments described demonstrate that (-)cathinone has an amphetamine-like releasing effect on physiological catecholamine storage sites. As the central and peripheral symptoms observed during khat consumption are probably due to this effect, it can be concluded that the widespread habit of chewing khat is pharmacologically analogous to amphetamine abuse.
1. Halbach, H.; Medical aspects of the chewing of khat leaves. Bull.W1d.Hlth.Org. 47 pp. 21-29, 1972
2. World Health Organization Advisory Group: Review of the pharmacology of khat. Bull.Narc. 32, pp. 83-93, 1980
3. Kalilc, P.; Hypermotility of the amphetamine type induced by a constitutent of khat leaves. Br.J.Pharmacol. 68, pp. 11-13, 1980
4. Zelger, J. and Carlini, E.; Anorexogenic effect of two amines obtained from Catha edulis (khat) in rats. Pharmaco.Biochem. Behay. 12, pp. 701-705, 1980
5. Valterio, C. and Kalix, P.; The effect of the alkaloid (-)cathinone on the motor activity in mice. Arch. Int . Pharmacodyn. 255, pp. 196-203, 1982
6. Kalix, P.; The amphetamine-like releasing effect of the alkaloid (-) cathinone on rat nucleus accumbens and rabbit caude nucleus. Prog. Neuropsychopharmacol. & Biol.Psychiat. 6, pp. 43-49, 1982
7. Kalix, P.; A constituent of khat leaves with amphetamine-like releasing properties. Europ.J.Pharmacol. 68, pp.213-215, 1980
8. Kalix, P.; Effect of the alkaloid (-)cathinone on the release of radioactivity from rabbit atria prelabelled with 3H-norepinephrine., Life Sci. 32, pp. 801-807, 1983.

Our valuable member P. Kalix has been with us since Monday, 20 May 2013.