Catha Edulis Forsk Research Articles

Khat chewing, cardiovascular diseases and other internal medical problems: The current situation and directions for future research

The leaves of khat (Catha edulis Forsk.) are chewed as a social habit for the central stimulant action of their cathinone content. This review summarizes the prevalence of the habit worldwide, the actions, uses, constituents and adverse health effects of khat chewing. There is growing concern about the health hazards of chronic khat chewing and this review concentrates on the adverse effects on health in the peripheral systems of the body, including the cardiovascular system and gastrointestinal tract. Comparisons are made with amphetamine and ecstasy in particular on the detrimental effects on the cardiovascular system. The underlying mechanisms of action of khat and its main constituent, cathinone, on the cardiovascular system are discussed. Links have been proposed between khat chewing and the incidence of myocardial infarction, dilated cardiomyopathy, vascular disease such as hypertension, cerebrovascular ischaemia and thromboembolism, diabetes, sexual dysfunction, duodenal ulcer and hepatitis. The evidence, however, is often based on limited numbers of case reports and only few prospective controlled studies have been undertaken. There is therefore an urgent need for more thorough case-control studies to be performed. This review outlines the current knowledge on the adverse health effects of khat chewing on the cardiovascular system and other internal medical problems, it assesses the evidence and the limitations of the studies and identifies the questions that future studies should address.

Concentration Levels of Essential and Non-essential Metals in Ethiopian Khat (Catha edulis Forsk)

The levels of essential (Ca, Mg, Mn, Fe, Zn, Cr, Cu, and Co) and non-essential (Cd and Pb) metal in six different varieties of Ethiopian khat (Catha edulis Forsk, an evergreen stimulant plant) commonly consumed in the country and exported to the neighboring countries were determined by flame atomic absorption spectrometry. Known weight of oven-dried khat samples were wet-digested using 2 mL of (69-72%) HNO(3) and 2 mL of (70%) HClO(4) for 2 h and 30 min at variable temperature (120-270°C). The mineral contents in the digests were analyzed using flame atomic absorption spectrometer. The following concentrations ranges in fresh-weight basis were recorded in decreasing order: Ca (1,038-2,173 µg/g) > Mg (478.2-812.3 µg/g) > Fe (53.95-82.83 µg/g) >Zn (5.18-9.40 µg/g) >Mn (6.98-8.66 µg/g) >Cu (1.85-5.53 µg/g) > Cr (0.66-3.47 µg/g) >Co (0.41-0.80 µg/g). A wide variation in the mineral contents of khat from different region of Ethiopia was noticed. The toxic metals (Pb and Cd) were not detected in all the samples analyzed.

Forensic analysis of hallucinogenic mushrooms and khat ( Catha edulisForsk) using cation-exchange liquid chromatography

Hallucinogenic mushrooms (e.g. Psilocybe and Panaeolus species) as well as leaves and young shoots of the khat tree ( Catha edulis Forsk) are illicit drugs in many countries. The exact concentration of the hallucinogenic alkaloids psilocin and psilocybin in mushrooms and the sympathomimetic alkaloids cathinone and cathine in khat is usually essential for jurisdiction. Facing an increasing number of mushroom and khat seizures by German customs authorities, a convenient comprehensive quantitative HPLC method based on cation-exchange liquid chromatography for these rather “exotic” drugs has been developed which avoids time-consuming multi-step sample preparation or chemical derivatization procedures. Using this method a number of different hallucinogenic fungi species and products that are mainly distributed via the internet have been analysed (dried and fresh Psilocybe cubensis Singer as well as P. cubensis collected from “grow boxes”, Panaeolus cyanescens Berkeley and Broome and so-called “philosopher stones” (sclerotia of Psilocybe species)). Highest total amounts of psilocin have been detected in dried P. cyanescens reaching up to 3.00 ± 0.24 mg per 100 mg. The distribution of khat alkaloids in different parts of the khat shoots has been studied. High concentrations of cathinone have not only been detected in leaves but also in green parts and barks of stalks. Additionally, the sample treatment for fresh mushroom and khat samples has been optimised. Highest amounts of alkaloids were found when fresh material was freeze-dried.

Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

BackgroundAn organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity.ResultsKhat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation.ConclusionKhat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.

Free radicals are present in human serum of Catha edulis Forsk (Khat) abusers

Objective Khat ( Catha edulis Forsk) is a naturally occurring drug with an amphetamine-like structure and action. It has been postulated that amphetamine induces free radical formation. On this basis, we have hypothesized that Khat may promote synthesis of reactive oxygen and nitrogen species in the same way that amphetamine promotes free radical production. Materials and methods Forty male subjects were enrolled in two groups: those with a chronic Khat chewing habit ( n = 20), and those without a chewing habit (controls; n = 20). Both groups were matched with regard to age. Total antioxidant capacity and cholinesterase (AChE) activity were assayed. Results This study showed that Khat consumption inhibited serum free radical scavenging enzymes, resulting in significant elevations in free radical loads ( p = 0.01; n = 20). We also showed that serum acetyl cholinesterase (AChE) was significantly inhibited in the Khat chewing group ( p = 0.002; n = 20). Conclusion These results show for the first time that Khat may contribute to high levels of free radicals. In addition, the presence of pesticides in Khat leaves is implicated in the inhibition of AChE activity.

The neuropsychopharmacological effects of Catha edulis in mice offspring born to mothers exposed during pregnancy and lactation

Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat during pregnancy, data are sparse with regard to the consequences of long-term exposure during pregnancy and lactation. The present work, therefore, was initiated to evaluate the neuropsychopharmacological effects of Catha edulis exposure during pregnancy and lactation in mice at postnatal day 28. To this effect, a lyophilized extract of khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water (negative control, CONT) were administered daily to pregnant mice from gestational day 6 until weaning. Neuropsychopharmacological measurements were done by making use of a battery of neurobehavioural and cognitive tests. Moreover, toxicity to liver and kidney was also evaluated by determining biochemical markers for possible tissue damage. K200 produced significant motor in-coordination and emotional instability; as revealed by impairment in both cliff avoidance (p < 0.01) and forelimb grip strength (p < 0.001), as well as by an increase in stereotyped behaviour such as grooming (p < 0.05), and in the percent of time spent in open arms (p < 0.05). On the other hand, K100 had an effect only on grip strength where a decrement was noted (p < 0.01). A different pattern emerged with AMP whilst it increased duration of sniffing (p < 0.05), neither grip strength nor the time spent in the open arm was affected compared with CONT. Increased latency to reach the goal box and the number of wrong decisions (p < 0.05) in both the learning and the recall tests was observed with K200 and AMP. By contrast, both doses of khat and AMP equally affected performance in the Y-maze (p < 0.05). Alterations in the biochemical indices of liver and kidney function were also noted with AMP and K200. These findings indicate that khat exposure produces dose-related central and peripheral effects during pregnancy and lactation which might pose a serious impediment to the physical and mental development of the offspring.

Effect of Dimethoate Residues on Soil Micro-arthropods Population in the Valley of Zendan,Yemen

The present study aimed to screen the effect of overuse of the insecticide Dimethoate and its residues within 0 -15 cm soil layer on the soil micro-arthropods population, which play a very important role in maintenance of the fertility of the soil. The valley of Zendan is located in Arhab Destrict, Sana’a Governorate, Yemen. The valley is about 50 km north-east of Sana’a city and this geographical area is a large producer of Qat(Catha edulis Forsk); the plant which most of the people in the country chew. In this study the valley divided into three stations, each station contained three treated substations and three control substations. The control substations selected from the farms, which are historically free from pesticides. Due care has been taken to insure that the treatedsub-stations were from the closest area to the control substations. The average use of Dimethoate 40% E.C is 1-2 ml/L water. The treatment replication was 1-3 times within the period of 2-3 weeks. In this study also, we analyzed the total concentration of Dimethoate, and its metabolite; Omethoate in the soil layer of 0-15 cm. The analysis of Dimethoate and Omethoate residues from representative soil samples covered the major part of the Zendan valley was done by the technique of LC-MS, and the results revealed that the detected levels ranged from 0.914 to 5.180mg/kg air-dried soil for Dimethoate residues and 0.001 to 0.067 mg/kg air-dried soil for Omethoate residues. For studying the effect of Dimethoate residues on the soil micro-arthropods population, soil samples from each substation were collected with core sampler. The soil micro-arthropods were extracted for 48 hours and collected in vials containing 70% alcohol by using the extraction funnels technique. The number and type of soil microarthropods extracted from each substation were separated and recorded and the data obtained was analyzed. Theoutcomes of the study revealed that Dimethoate and Omethoate residues are beyond the Total Threshold Limit Concentration (TTLC) and significantly reduced the population of the non-target soil micro-arthropods that included mainly mites, collembolans, beetle larvae, trips, cutworms, symphyla and seed corn maggot. Mites and collembolanswere the most affected micro-arthropods by Dimethoate and Omethoate residues. The reduction in the soil microarthropods population varied from 59% to 69% as compared to its population in control substations. The maximum decline of soil microarthropods was found to be in substations where the highest residues of Dimethoate and Omethoate were recorded. Thus indiscriminate use of pesticides such as Dimethoate will definitely affect the soil fertility in the area and that will reduce the crop yield in future. @JASEM

Khat rings twice: Khat-induced thrombosis in two vascular territories

The psychostimulating herbal drug Khat (Catha edulis Forsk.) is cultivated and used as a recreational drug in East Africa and the Arabian Peninsula. The chewing habit has now spread to ethnic communities in the rest of the world. Historically, Khat is used at funerals, marriages and business deals.

Human khat ( Catha edulis) chewers have elevated plasma leptin and nonesterified fatty acids

In this study, the effect of regular khat ( Catha edulis Forsk) chewing (200 and 400 g) in humans on plasma leptin, nonesterified fatty acid, triacyglycerol, and total cholesterol levels was investigated. The results presented show that khat chewing increases plasma leptin concentration particularly in individuals who chew 400 g of khat leaves. The significance of increased plasma leptin is in explaining the underlying mechanism of the observed effects associated with khat chewing such as loss of appetite, decreased body weight, and hyperthermia. The decreased body weight was evident from the significantly lower body mass index of the khat leaves chewers group as compared to the non–khat leaves chewers group (control). Moreover, like leptin, the plasma levels of nonesterified fatty acids were significantly higher in those chewing 400 g of khat leaves. On the other hand, the plasma levels of triacylglycerol were significantly lower in the 2 khat-chewers groups (200 and 400 g of khat leaves), whereas plasma cholesterol levels were not affected by the 2 levels of khat leaves used in this study. The significance of these results may suggest that khat leaves may contain a component(s) that has the ability to reduce body weight via decreasing appetite.

In vitro study of the effects of khat ( Catha edulis Forsk) extract on isolated mouse interstitial cells

Isolated mouse interstitial cells were incubated with different concentrations of khat ( Catha edulis) extract (0.06 mg/ml, 0.6 mg/ml, 6 mg/ml, 30 mg/ml and 60 mg/ml) and cell viability as well as testosterone concentration measured at 30 min intervals over a 3 h incubation period. High concentrations of khat extract (30 mg/ml and 60 mg/ml) significantly inhibited testosterone production while low concentrations (0.06 mg/ml, 0.6 mg/ml and 6 mg/ml) significantly stimulated ( P < 0.05) testosterone production by mouse interstitial cells. Similarly, at concentrations of 30 mg/ml and 60 mg/ml, there was a significant decrease in interstitial cell viability, whereas at 0.06 mg/ml, 0.6 mg/ml and 6 mg/ml there was no significant decrease. There was only a weak correlation ( r = 0.39) between testosterone production and viable interstitial cells. We postulate that khat extract at high concentrations may cause reproductive function impairment in the user but at low concentrations, may enhance testosterone production with accompanying effects on reproductive functions in male mice.

Pro‐oxidant effect of khat (catha edulis forsk) on liver and brain of rats

Pro‐oxidant effect of khat (catha edulis forsk) on liver and brain of rats

Determination of pesticide residues in Khat leaves by solid-phase extraction and high-performance liquid chromatography

The purpose of this investigation is to develop a simple method for the assessment of pesticides in Khat leaves, Catha edulis FORSK. (Celastraceae) shrub, chewed by about 60 % of the Yemeni people, producing amphetamine-like psychostimulation. The first procedures involve solid-phase extraction using Adsorbex® RP-C18 and Bakerbond® RP-C18 disposable cartridges with 40 % acetonitrile for elution. Isocratic and gradient analysis was carried out by means of high-performance liquid chromatography using different stationary phases to analyse methidathion, peconazole and dimethoate. An UltrasphereODS RP-18-column with UV-detection at 210 nm and 80/20 % (v/v) acetonitrile/water as mobile phase (isocratic) was used to determine the content of methidathion, peconazole and dimethoate (detection limit 20-25 ng). The method was validated with fortified samples at pesticide concentration of 0.1 mg/ml. Average recoveries ranging from 97.9 and 101.6% with a relative standard deviation (RSD) of 1.7-3.8 %. Each recovery analysis was repeated four times. Limits of detection ranged from the analytical procedures were applied to 5 samples of khat and no detectable amounts of pesticides were found in any sample under the conditions described.

The Role of Bcl-2 in Apoptosis Induced by khat (Catha Edulis) in Acute Myeloid Leukemia Cell Lines.

The herbal drug khat (Catha edulis Forsk.) is habitually used in Eastern Africa and the Middle East. The pharmacological activity of khat is due to its alkaloid fraction which initiates a rapid release of monoamine neurotransmitters from nerve terminals when ingested. Extracts from khat have been shown to induce cell death caspase-dependent apoptosis in human leukaemia cells. In this study, apoptotic sensitivity is correlated with endogenous protein expression of the anti-apoptogen Bcl-2, as well as transfection enforced over expression of Bcl-2. Exposure of a panel of human leukaemia cell lines to khat extract resulted in the development of similar apoptotic morphotypes. The sensitivity of the cell lines to khat induced apoptosis revealed a trend of inverse correlation with endogenous levels of Bcl-2. Stable or transient transfection of Bcl-2 inhibited khat-induced apoptosis, and the threshold for khat-induced apoptosis was lowered by blocking Bcl-2 synthesis with small interfering RNA. Together, these data suggest Bcl-2 modulation as a possible mechanistic pathway through which khat-induced apoptosis may occur.

The potential adverse effects of habitual use of Catha edulis (khat)

The habit of Catha edulis Forsk (khat) chewing has prevailed for centuries among populations in the horn of Africa and the Arabian peninsula. Fresh leaves of Catha edulis are customarily chewed to attain a state of stimulation. The fact that cathinone has a closer structural similarity with amphetamine, and both share common pharmacodynamic features, led to the conclusion that cathinone is the most important active ingredient of Catha edulis, which causes the major pharmacological effects. Problems associated with repeated consumption of Catha edulis leaves are becoming evident. Literature surveys and clinical diagnostic studies revealed an association with prevalence of psychiatric morbidity. Repeated intermittent oral administration of Catha edulis to laboratory animals lead to development and expression of locomotor sensitisation. Catha edulis also leads to several peripheral effects that include increases in blood pressure and has been associated with the increased incidence of acute coronary vasospasm and myocardial infarction. Catha edulis also accounts for a number of gastrointestinal tract problems, oesophagitis, gastritis and delay intestinal absorption, as well as the development of oral keratotic white lesions at the site of chewing. Administration of Catha edulis extracts showed a deranged systemic capacity to handle oxidative radicals and induces cytotoxic effects in cells of liver and kidney, as well as induction of cell death in various human leukaemia cell lines and in peripheral human blood leukocytes.

Khat chewing and its socio-demographic correlates among the staff of Jimma University

Abstract Background: Khat (Catha edulis forsk) contains a psychoactive substance called cathinone, which produces central stimulation analogous to amphetamine. It is widely abused in East Africa in general and in Ethiopia in particular for various purposes. Habitual use of khat renders certain influence on the physical, psychological and economical well being of the community. Objective: The aim of this study is to determine the prevalence and socio-demographic profile of khat chewing and other associated factors relating to the technical staff of Jimma hospital and the academic staff of Jimma University (JU). Methods: A cross-sectional survey on 400 JU staff was conducted using a self-administered structured questionnaire in JU, Jimma town, Southwest Ethiopia, from Jan. to Feb 2003. Results: The current prevalence of khat chewing was 30.8%. More males (33.0%) than females, Muslims (49.0%) than other religious groups, Tigres (42.9%) than other ethnic groups, Technical (33.8%) than Academic staff, married (32.4%) than singles, age group 18-24 years (34.4%) than other age groups, and general practitioners (40.5%) than other professional groups were found to be khat chewers. About 50.4% of the khat chewers have one or more times missed their regular work at JU because of chewing, and 54.5% of the chewers used to come late chewing khat or leave their work early to chew khat. Male sex (x2=4.01, P=0.0319) being Muslim (x2=19.839, P=0.0005) were significantly associated with khat chewing. Smoking and alcohol intake also showed a statistically significant association with the habit of khat chewing. Conclusion: A fairly large proportion of Jimma University staff, which are assumed to be models for the rest of the population, chew khat and this has a strong negative impact on service delivery and the teaching-learning process as they miss their regular work because of the practice. [Ethiop.J.Health Dev. 2004;18(3):179-184]

Driving under the influence of khat—alkaloid concentrations and observations in forensic cases

The use of the herbal stimulant khat ( Catha edulis FORSK) is maintained by immigrants from countries where it is part of their cultural life (Arabian Peninsula and eastern Africa). In western countries the drug and its effects are largely unknown and no experience in evaluating impairment symptoms due to the khat-alkaloids, e.g. cathinone, cathine and norephedrine exists. Blood and urine samples from khat users involved in 19 cases of suspected driving under the influence of drugs were analysed and correlated with the results of medical examination and police officer reports. In 3 cases impaired driving and in 10 cases marked impairment of psychophysical functions was observed such as effects on the nervous system (slow pupil reaction to light, dry mouth, increased heart-rate), trembling, restlessness/nervousness, daze/apathy/dullness, impairment of attention, walking and standing on one leg. However, the alkaloid concentrations assayed in blood did not correlate with the impairment symptoms. Apart from an acute phase of indirect sympathomimetic action the development of habituation and withdrawal symptoms must also be considered in explaining the diversity of effects observed. From these results it can be concluded that chewing khat may severely impair driving ability, but may also be without noticeable effects.

The effect of khat chewing on gallbladder motility in a group of volunteers

An increase in the prevalence of gallstones has been reported from the Middle East and the Republic of Yemen. Changing dietary habits and obesity are thought to be responsible but other local factors may contribute such as chewing the leaves of the khat plant ( Catha edulis Forsk.) which is a widespread social custom in Yemen. We have studied the effects of khat chewing on gallbladder motility in a group of 10 healthy volunteers. All subjects underwent ultrasound measurements of gallbladder volume after chewing khat leaves or lettuce, which was used as the control. Results were compared after chewing for up to 2 h in the fasting state and in response to a fatty meal. There was no significant change in gallbladder volume after chewing khat compared with lettuce in the fasting state ( P=0.7) or in gallbladder emptying after a fatty meal ( P=0.4) and we conclude that khat chewing has no clinically significant effect on gallbladder motility.

Khat: pharmacological and medical aspects and its social use in Yemen.

Fresh leaves of the khat tree (Catha edulis Forsk.) are chewed for their euphoric properties in East Africa and parts of the Middle East, such as The Yemen. This review describes the history, cultivation and constituents of khat, and the social aspects of khat chewing in Yemen. The major pharmacologically active constituent of the fresh leaves is (--)-S-cathinone. The pharmacology of (--)-S-cathinone in the central nervous system and the peripheral effects are described. (--)-S-Cathinone is regarded as an amphetamine-like sympathomimetic amine and this mechanism of action is discussed in relation to the central stimulant actions and the cardiovascular effects of increasing blood pressure and heart rate. The risk factors associated with khat chewing are described, with emphasis on the reported increased incidence of acute myocardial infarction.

Mutagenic and Carcinogenic Activity of Khat (Catha edulis Forsk) Component

Mutagenic and Carcinogenic Activity of Khat (Catha edulis Forsk) Component

Constipating and spasmolytic effects of Khat (Catha edulis Forsk) in experimental animals.

The constipating and spasmolytic effects of Catha edulis Forsk (Khat) were investigated in whole mice and on isolated guinea pig ileum. D-amphetamine was employed in both experiments for comparison. The total distance travelled (expressed in percentage) by charcoal suspension in the gastrointestinal tract of mice was determined before and after khat administration. The procedure was repeated with amphetamine and normal saline. The results were compared. Amplitudes of contraction were recorded with standard spasmogens, histamine and carbachol, in the presence and absence of khat extract of different concentrations. The same was done with amphetamine. Khat extract was observed to reduce the total distance travelled by charcoal suspension, comparable to D-amphetamine. The spasmogenic effects of both histamine and carbachol were observed to be antagonized by the khat extract in a concentration-dependent manner. The antispasmodic effect of khat extract was observed to be similar to that of D-amphetamine.