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The administration of the flavonid fraction, isolated from Khat (Catha edulis Forsk), in a dose of 200 mg/kg orally, produced a significant anti-inflammatory activity against the carrageenan induced paw oedema and cotton pellet granuloma in albino rats. The results were comparable with the standard anti-inflammatory drug oxyphenbutazone.
A chloroform extract of Khat (Catha edulis) leaves was used to study the cytotoxic activity on KB, 1BR.3, and XP2Bi cells. Log phase cell survival curves showed an LD50 of 40 ng/ml for KB cells. 1BR.3 and XP2Bi cells were biphasic in their response to the extract during log phase, with an LD50 of 20 and 75 ng/ml, respectively. Stationary phase cells were unaffected by the extract. DNA and RNA synthesis inhibition was studied using radiolabeled thymidine or uridine to measure the amount of extract that inhibits the synthesis to 50% of the untreated control cells. DNA synthesis was inhibited by 45, 60 and 200 ng/ml and RNA synthesis by 24, 17 and 58 ng/ml in 1BR.3, XP2Bi and KB cells, respectively. Protein synthesis was inhibited to 15-20% of untreated control cells by a dose of 40 ng/ml in all the cells studied. From this work, it is apparent that the main cause of cytotoxicity of Khat extract may be the inhibition of de novo RNA synthesis. Our results suggest that this effect is exerted on all cells used in this study and that KB cells demonstrate a higher resistance to the toxic component.
The effects of acute and chronic administration of an extract of Catha edulis on the heart of the toad were investigated. ECG and ventricular action potential were recorded simultaneously from the surface of the heart of spinal pithed toads before and after administration of different doses of khat extract. Acute treatment resulted in a dose-dependent chronotropic effect and an increase in the amplitude of ventricular action potential. Chronic treatment on the other hand resulted in a negative chronotropic effect and a reduction in the amplitude of ventricular action potential. The observed responses are explained on the basis of the catecholamine releasing effect of components of khat extract.
Khat, the leaves of Catha edulis Forsk. (Celastraceae), is widely used as a stimulant in East Africa and the Arab Peninsula. Samples from the most important markets of Ethiopia, Kenya, North Yemen and Madagascar were analysed with high-performance liquid chromatography (HPLC) concerning their khatamine content (phenylpropyl and phenylpentenylamines). The variability of khatamines depending on origin, type and quality is discussed. In many samples a good correlation between the amount of cathinone, the main CNS-active compound, and quality estimation (price) of dealers and consumers was found.
Ever since the introduction of the alkaloid ephedrine as an anti-asthmatic, the CNS stimulatory effects of this sympathomimetic have been a problem in therapy. Indeed, the use of ephedrine is not only limited by its cardiovascular effects, but also by the occurrence of insomnia, restlessness and anxiety. Exceptionally, ephedrine may even induce toxic psychosis, and the possibility of this side effect has recently received renewed attention. Besides ephedrine, the ephedra plant contains some norpseudoephedrine. This substance is also called cathine, because it is a major alkaloid of Catha edulis or khat, a plant that is widely used as a stimulant in certain countries of East Africa and of the Arab Peninsula. The effects of khat have been explained formerly by those of cathine; some time ago, however, the labile alkaloid cathinone was discovered in khat. This substance is the keto-analog of cathine; it is therefore more lipophilic and penetrates easily to its sites of action in the central nervous system. Indeed, cathinone has been found to be a highly potent CNS stimulant and it is now known to be the main psychoactive constituent of khat; the results of various in vitro and in vivo studies indicate that cathinone must be considered a natural amphetamine. In confirmation of this view, it has recently been demonstrated that cathinone has in humans marked euphorigenic and psychostimulant effects. As the case may be, these findings may lead, together with epidemiological data, to a reconsideration of the use of khat as a stimulant and social drug.
Genotoxicity of the methanolic extract of khat (Catha edulis) has been evaluated on the male germ cells using the dominant lethal assay procedure in Swiss albino mice. The extract was administered at a dose of 500 mg/kg orally once daily, for five days. Following this sub-acute dose regimen, the effect of khat was studied during the different stages of spermatogenic cycle on the rate of pregnancy and post-implantation losses. Khat reduced the percent pregnancy rates and increased the mean post-implantation losses in the treated group. The increase was found to be statistically significant in the post-meiotic stages.
Cytological effects of khat (Catha edulis), a popular drug of abuse from Southern Arabia and Eastern Africa, have been studied in Swiss albino mice. The studies on the somatic system involved the use of micronucleus test and the cytological analysis of the mitotic index in the femoral cells of mice. In the micronucleus test, the mice were treated with different doses of khat extract (125, 250 and 500 mg/kg, p.o.) 30 and 6 hours before sacrificing the animals. The polychromatic erythrocytes were screened for the induction of micronuclei. For the analysis of bone marrow cytotoxicity, the mice were treated with the dose of 125, 250 and 500 mg/kg, body weight, p.o. daily for 5 consecutive days. The animals were sacrificed and the femoral cells were microscopically examined for the mitoses. Following the same schedule of treatment, studies on the cytogenetic analysis of meiotic chromosomal aberrations and the sperm head abnormality were undertaken. Khat extract significantly increased the frequency of micronucleated polychromatic erythrocytes, induced bone marrow depression and reduced the mitotic index of the somatic cells. It induced significant chromosomal aberrations viz., aneuploids, autosomal univalents, univalents of the sex chromosomes and polyploids. The frequency of abnormal sperms was also increased.
The pattern of use of khat (Catha edulis Forsk), alcohol, cigarettes and tranquillizers among 479 medical and paramedical students in a boarding college in northwestern Ethiopia was studied by an anonymous self-administered questionnaire. The survey coverage rate was 98.8%. The majority of students were males (82.6%) and their average age was 21.2 years. The prevalence rate of current use of alcohol, cigarettes, khat and tranquillizers was 31.1%, 26.3%, 22.3% and 7.7%, respectively. These substances were also used in combinations, the most frequent involved khat, alcohol and cigarettes. Use of khat varied by the type of training (medical/paramedical) and by phase of medical education (preclinical/clinical). These variations were also apparent when data were analysed by sex and frequency of khat use. It appears that the pattern of khat use among university students is similar to that reported for substance abuse in other countries. Because of the economic importance of khat in the Ethiopian economy, its control may be difficult at present.
The effect of khat (Catha edulis Forsk., family Celastraceae), a plant used for its stimulant effects in eastern Africa and southern Arabia, has until recently been attributed to the pharmacological action of d-norpseudoephedrine, also known as cathine. The isolation in 1975 of cathinone revived an earlier suggestion that the fresh leaves contained a substance more potent than cathine. The pharmacological assays reported on in this paper appear to confirm the higher stimulant capacity of cathinone. This substance produces qualitatively similar locomotor stimulation in mice and comparable stereotypy in rats as amphetamine does, although it is approximately half as active. The results obtained after pre-treatment with reserpine or alpha-methyl-p-tyrosine, which interfere with the catecholamine system, strongly suggest that cathinone interacts with brain catecholamines by an indirect mechanism and, most probably, by affecting neurotransmitter release of the labile pool.
d-Norpseudoephedrine, a central stimulant present in Catha edulis, is excreted unchanged in human urine. The alkaloid was detected in urine 30-50 min after ingestion of synthetic d-norpseudoephedrine, and trace amounts of the drug could still be detected 24 hr later. Approximately 40% of ingested d-norpseudoephedrine was recovered in urine in the first 6 hr.
Bilateral optic atrophy is reported in two patients who, although they were long-standing users of the leaves of Catha edulis, had chewed larger quantities than usual. Since the leaves of this plant are used widely throughout its native area as the source of a mildly stimulant narcotic, the effect in these cases may be an idiosyncratic reaction to an unusually large dose.
Catha edulis, or khat, a plant indigenous to Yemen, Ethiopia, and East Africa, has sympathomimetic and euphoriant effects. Its role in the economic, social, and political lives of people in North and South Yemen and certain clinical and psychiatric aspects are discussed.
The mutagenicity of a methanolic extract of khat has been evaluated on male germ cells using the dominant lethal test in albino mice. An aqueous solution of khat extract was administered orally in doses of 50, 100 and 200 mg/kg body wt., respectively, to 3 different groups of male mice for a period of 6 weeks. At the end of treatment each male mouse was allowed to mate with 2 different groups of 3 females each, on 2 consecutive weeks. These females were necropsied on the 13th day of their presumptive mating, and the number of implants in each female and the ratio of live and dead embryos were determined. The results of this study showed that the treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in the rate of fertility in the first week after mating, which was irreversible in the second week at the highest dose (200 mg/kg). Khat extract also induced post-implantation loss during the first week following treatment. However, a comparison of the results of the first and second weeks showed a reversible pattern of dominant lethality.
The possibility that phenylalkylamines (cathinone and cathine) of khat, like amphetamines, are amine oxidase inhibitors with clinical significance is evaluated. Results show that khat chewing induces a significant increase in blood pressure, body temperature and urinary catecholamines in khat naive subjects. On the other hand, in habitual consumers a significant enhancement only of blood pressure is observed. Urinary concentrations of vanilmandelic acid show an inhibitory trend in both groups of subjects. This has been related to a decrease in catecholamine deamination. In fact, oxidative deamination of benzylamine catalyzed by beef plasma amine oxidase is non-competitively inhibited in vitro by cathinone (Ki = 0.05 mM) and cathine (Ki = 10 mM) as well as by amphetamine (Ki = 7.9 mM).
A large number of people in East Africa and Southern Arabia chew khat leaves because of its pleasurable and stimulating effects. Due to its habit forming property, the khat has been classified as a "Substance of Abuse" by the World Health Organization. In view of the large number of medical problems reported in khat chewers, the present study was undertaken to investigate the chronic toxicity of khat in mice. Three groups of mice were treated with aqueous solution of khat extract in the dose of 50, 100, and 200 mg/kg. body weight daily by oral intubation route for 6 weeks. The results indicated a dose-dependent decrease in body weight, an increase in the incidence of mortality and induction of site specific body and eye lesions. The histopathological examination of the lesions revealed reactive hyperplasia and necrosis in the lymphoid tissues. The necrotic areas in the subcutaneous tissues showed the presence of numerous polymorphs.
There have been relatively few reported cases of psychosis due to khat usage despite its heavy consumption in certain East African and Arabian countries. Four cases have been reported in the UK. We report here on three further cases of psychotic reactions to this substance in Somalian males, and emphasize the need to be aware of khat as a potential substance of abuse, with both medical and psychiatric complications. The features of khat psychoses are described and the relationship to amphetamine and ephedrine psychoses is discussed. The forensic aspects of two of the cases which involved homicide and combined homicide and suicide are highlighted, as is the possible role of social dislocation from the culture of origin.
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