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Ethnopharmacological Relevance: Khat (Catha edulis (Vahl) Forssk.) is a herb from the Celastraceae family (also known as qat, gaad, or mirra) that is widely-consumed in East Africa and in the Arabian peninsula. The green leaves and small stems are consumed primarily at recreational and social gatherings, and medicinally for their antidiabetic and appetite-suppression effects., Aims: The objectives of this study were to determine the effects of khat and its active alkaloid, cathinone, on food intake and body weight in mice maintained on a high-fat diet, and to investigate its mechanism of action in white adipose tissue and in the hypothalamus., Materials & Method: Adult male mice (C57BL/6J) were fed a high fat diet (HFD) for 8 weeks (n = 30), then divided into 5 groups and treated daily for a further 8 weeks with HFD + vehicle [control (HFD)], HFD + 15 mg/kg orlistat (HFDO), HFD + 200 mg/kg khat extract (HFDK200), HFD + 400 mg/kg khat extract (HFDK400) and HFD + 3.2 mg/kg cathinone (HFDCAT). Treatments were carried out once daily by gastric gavage. Blood and tissue samples were collected for biochemical, hormonal and gene expression analyses., Results: Khat extracts and orlistat treatment significantly reduced weight gain as compared to control mice on HFD, and cathinone administration completely prevented weight gain in mice fed on HFD. Khat treatment caused a marked reduction in body fat and in serum triglycerides. A dose-dependent effect of khat was observed in reducing serum leptin concentrations. Analysis of gene expression in adipose tissue revealed a significant upregulation of two lipolysis pathway genes:(adipose triglyceride lipase (PNPLA-2) and hormone-sensitive lipase (LIPE). In the hypothalamic there was a significant (P < 0.05) upregulation of agouti-related peptide (AgRP) and cocaine-amphetamine regulated transcript (CART) genes in the HFDK400 and HFDCAT groups., Conclusion: Cathinone treatment blocked body weight gain, while high dose khat extract significantly reduced the weight gain of mice on an obesogenic diet through stimulation of lipolysis in white adipose tissue., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Khat (Catha edulis) contains cathinone, an active principal that is customarily used as a psychostimulant that wards off fatigue and to some extent used as an aphrodisiac., Aim of Study: To investigate effects of escalating doses of cathinone on hormone expression by different anterior pituitary cell types using specific antibodies., Material and Methods: Eleven vervet monkeys (6 males and 5 females) divided into tests (n=9) and controls (n=2) were used. Animals were allocated as group I (saline controls), group II (0.8 mg/kg), group III (3.2 mg/kg) and group IV (6.4 mg/kg) of cathinone. All treatments were via oral route at alternate days of each week. At the end of 4-month treatment phase, GnRH agonist (ZOLADEX) was administered to group II (low dose) and group IV (high dose) alongside cathinone for 2 additional weeks., Results: High cathinone dose at long-term exposure caused proliferation of gonadotrophs but decrease in lactotrophs and corticotrophs in anterior pituitary sections of animals while effect of low dose on these cells was insignificant. Subsequent GnRH agonist co-treatment with low and high cathinone doses enhanced gonadotroph proliferation but no change on decline of lactotrophs and corticotrophs., Conclusion: We believe that there was a possible potentiation of cathinone on pituitary hormone synthesis thereby influencing reproductive function. Suppression of corticotrophic and lactotrophic functions suggest lowering of stress levels and modulation of reproductive function based on dose level and chronicity of exposure. The findings are consistent with the hypothesis that cathinone interferes with pituitary cell integrity and consequently target organs, but further studies are required to address the precise mechanism underlying this phenomenon., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Khat (Catha edulis, Forsk) is a drug widely used in countries around the Red Sea (East-Africa and Arabian Peninsula). In Germany khat chewing is illegal but nevertheless an often observed habit in immigrants from this region. This study investigates the interrelation between immigrants acculturation processes and traditional khat chewing habits., Materials and Methods: Sixty-one khat chewers (14 female) from East-African countries were interviewed about their khat chewing habits and acculturation strategy using standardized questionnaires., Results: Results indicate that immigrants׳ khat chewing behaviors are similar to what is common in countries with traditional khat use. But khat chewing tended to be less among immigrants who were relatively more oriented towards their cultures of origin. Chewing khat was subjectively considered to help coping with problems, to forget bad memories and to concentrate better., Conclusions: It was concluded that khat chewing serves a functional use of coping with stressful events in the present or in the past within this sample., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: To understand the role of khat (Catha edulis) use on the aberrations in appetite and weight which are common comorbidities for khat and other amphetamine users., Materials and Methods: We provide a comprehensive overview and conceptual summary of the historical cultural use of khat as a natural stimulant and describe the similarities and differences between cathinone (the main psychoactive constituent of khat) and amphetamine highlighting the limited literature on the neurophysiology of appetite and subsequent weight effects of khat., Results: Animal and some human studies indicate that khat produces appetite suppression, although little is known about mechanisms of this effect. Both direct and indirect effects of khat stem from multiple factors including behavioral, chemical and neurophysiological effects on appetite and metabolism. Classic and newly identified appetite hormones have not been explored sufficiently in the study of appetite and khat use. Unique methodological challenges and opportunities are encountered when examining effects of khat and cathinone including khat-specific medical comorbidities, unique route of administration, differential patterns of behavioral effects relative to amphetamines and the nascent state of our understanding of the neurobiology of this drug., Conclusion: A considerable amount of work remains in the study of the appetite effects of khat chewing and outline a program of research that could inform our understanding of this natural amphetamine׳s appetite effects and help prepare health care workers for the unique health effects of this drug., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Cathinone hydrochloride is an active principle of the khat plant (Catha edulis) that produces pleasurable and stimulating effects in khat chewers. To the best of our knowledge no data of cathinone on oxidative stress in limbic areas of mice is available. This is the first study of cathinone on oxidative stress in limbic areas of the brain in Swiss albino male mice., Materials and Methods: The animals were divided into four groups. Group-I was the control group and received vehicle, while groups-II to IV received (-)-cathinone hydrochloride (0.125, 0.25 and 0.5 mg/kg body wt., i.p.) once daily for 15 days., Results: The level of lipid peroxidation (LPO) was elevated dose-dependently and was significant (p<0.05, p<0.01) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. In contrast, the content of reduced glutathione (GSH) was decreased significantly (p<0.01, p<0.001) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. The activity of antioxidant enzymes (GPx, GR, GST, CAT, and SOD) was also decreased dose-dependently: the decreased activity of GPx, GR, catalase and SOD was significant with doses of 0.25 and 0.5 mg of cathinone as compared to control group, while the activity of GST was decreased dose-dependently and was significant with 0.5mg of cathinone as compared to control group., Conclusions: The results indicate that the cathinone generated oxidative stress hampered antioxidant enzymes, glutathione and lipid peroxidation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The escalating use of khat (Catha edulis) in East Africa and Arabia is a major concern for public health. Yet little is known about the impact of khat on behavior. There has been no study in the region to assess the extent to which dependence syndrome is associated with khat use in this population., Aim of the Study: To examine psychometric properties of the Severity of Dependence Scale-Khat (SDS-khat), gender differences in patterns of khat use and dependence, and the extent to which age moderated the link between gender and khat dependence., Materials and Methods: Two-hundred and seventy khat chewers recruited in two Yemeni cities completed face-to-face interviews asking about demographics and patterns of khat use. Validity of SDS-khat was examined by the principle component analysis and reliability of the scale was tested by Cronbach׳s alpha. A series of chi-square tests and analysis of variances (ANOVAs) were conducted to examine gender differences in khat use variables., Results: The results indicated that the mean age of khat chewers was 30.52 years (95% CI: 29.34, 31.70) and 52% of them were males. The SDS-khat was found to have two factors with moderate reliability. This pattern was consistent when the analysis was conducted in the entire sample and in each gender. Male khat chewers reported more symptoms related to khat dependence than female chewers. A significant gender by age interaction in SDS-khat levels (p=0.013) revealed a positive association between age and khat dependence in women only., Conclusion: These results provide initial support for the use of SDS-khat in the assessment of khat dependence in Yemen. Gender differences in khat use patterns and dependence observed in this study call the need for more studies carefully examining the role of gender in khat research., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims of Study: The habit of khat chewing has been associated with increased risk of systemic and oral disease. Although research has been conducted on the affects of khat on oral epithelial cells, little is known about its influence on immune cells. This study examined the biological effects of khat on the phenotype and function of peripheral blood mononuclear cells (PBMCs)., Material and Methods: Khat-stimulated PBMCs were examined for signs of cytotoxicity, apoptosis and changes in cell surface receptor and cytokine expression. Khat-induced regulation of transcription factors and stress-related factors were examined, as was PBMC phagocytic activity against oral bacteria., Results: Khat was cytotoxic to PBMC in a dose- and time-dependent manner and cell death was mediated by apoptosis. Khat-treated PBMC showed increased expression of co-stimulatory molecules (CD80, CD86 and MHC II) and pattern recognition receptors (TLR-2, TLR-4 and TREM-1) but secretion of inflammatory cytokines (TNFα, IL-6, CCL5, CXCL8) was inhibited. In contrast, khat induced an increase in the anti-inflammatory cytokine IL-10 as well as IL-2, IFN-γ, FasL and HSP70. These khat-induced alterations were accompanied by increased expression of transcription factors p38 MAPK and HIF-1α, whilst expression of NFκB p65 was inhibited. Although the ability of PBMC to phagocytose dextran and oral bacteria was inhibited, production of reactive oxygen species was increased., Conclusion: These data suggest that khat may severely influence the effectiveness of immune surveillance and anti-microbial capacity of PBMCs., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Khat is a plant with psychostimulant properties whose parts, mainly leaves and twigs, are chewed for its euphoriant effects. Khat use and ethanol abuse are increasingly becoming global health concerns especially among many disadvantaged social groups. The present studies were undertaken to investigate seizure susceptibility and responses following chronic co-administration of khat and ethanol., Materials and Methods: Juvenile male Sprague-Dawley (SD) rats were administered khat, ethanol or combined khat and ethanol twice daily for 28 days by gavage. Khat-treated animals received 2 g/kg or 4 g/kg body weight continuously for the study period. Ethanol-treated animals received 20% ethanol at a dose of 4 g/kg body weight. The convulsant, pentylenetetrazol (PTZ), was administered intraperitoneally at a dose of 40 mg/kg body weight. Seizure responses were recorded., Results: Twice-daily dosing of khat did not produce inhibition of weight gain. Khat alone, combined khat and 20% ethanol, but not 20% ethanol alone, significantly reduced the latency to seize. Khat treatment at 2 g/kg but not 4 g/kg body weight also significantly increased the duration of seizures. Conversely, combined khat and ethanol reduced the duration of seizures compared to controls. Ethanol alone reduced the seizure severity while khat alone, and combined khat and ethanol, produced close to the maximum seizure severity., Conclusions: These data suggest that combined moderate to high dose khat and ethanol co-dependence produce a greater deleterious CNS effect than either drug alone. Future studies will address neurochemical effects, in addition to neuroadaptations, resulting from coabuse of these drugs., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aim: In this article, we comment on the current international discourse on khat, we highlight pitfalls and and suggest balanced national international regulatory actions., Method: A brief an focussed review of the available literature on khat and health and examples from our own research are provided., Results: The use patterns of catha edulis (khat) have changed throughout the last decades. During this period khat has had a remarkable economic boom and developed from a niche crop to the backbone of the regional economy. Now it contributes to the livelihoods of millions of people. Today, khat use is often the proverbial "Door in the wall" for large parts of the populations in African and Arab countries beyond the traditional user groups. Its use is often excessive and not restricted by social regulation mechanisms. Under such conditions, problematic khat use patterns develop rapidly, exemplified by the growing group of binge users, and it gets even prevalent among especially vulnerable groups such as children, people with mental disorders or pregnant women. The currently existing scientific evidence suggests that problematic use patterns not the use per se can be linked to numerous health consequences., Conclusion: This paper argues that changed patterns of khat use are a burden for some of the most underdeveloped countries in the world. But the debate around khat is stuck between extreme poles arguing for prohibition or for de-regulation. Here, we call for a balanced action of governments and international organizations leaving behind the decades of debilitating debate pro vs. contra scheduling and banning khat leaves. Instead, regulation and harm-reduction measures are urgently needed. We suggest a number of steps that should be taken immediately to better understand current khat use patterns, to address noxious excesses and to relieve suffering., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: The study aims to review and analyse the varied East African discourses on the effects of khat use on libido, fertility, transmission of HIV, prostitution and rape., Materials and Methods: The data were gathered between 2004 and 2009 in Kenya and Uganda. Between 2004 and 2005 across Kenya and Uganda a broad survey approach was adopted, involving identification of and travel to production areas, interviews with producers and consumers in rural and urban settings. In addition, a survey of 300 Ugandan consumers was carried out in late 2004. Between 2007 and 2009, an in-depth study of khat production, trade and consumption was conducted in Uganda. This study also employed a mixture of methods, including key informant interviews participant-observation and a questionnaire survey administered to 210 khat consumers., Results: Khat is associated, by consumers and its detractors alike, with changes in libido and sexual performance. Although there is no evidence to support their claims, detractors of khat use argue that khat causes sexual violence, causes women to enter sex work, and that chewing causes the spread of sexually transmitted diseases, including the HIV virus., Conclusions: In East Africa the discourse on khat and sex has led to consumption of the substances being associated by many people with uncontrolled sexual behaviour. There is no evidence that khat use fuels promiscuity, commercial sex, sexually transmitted diseases or rape. The current discourse on khat and sex touches on all these topics. Local religious and political leaders invoke khat use as a cause of what they argue is a breakdown of morals and social order. In Kenya and Uganda it is women khat consumers who are seen as sexually uncontrolled. In Uganda, the argument is extended even to men: with male khat chewers labelled as prone to commit rape., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aims: Existing in vitro and in vivo data suggest that khat may have a favorable effect on periodontal microbiota. The purpose of this study was to assess the effect of khat chewing on major periodontal pathogens in subgingival plaque samples from subjects with chronic periodontitis., Materials and Methods: 40 subgingival plaque samples were obtained from periodontitis and healthy sites of 10 khat chewers (40 y median age) and 10 khat non-chewers (37.5 y median age) with chronic periodontitis. Absolute and relative counts of 6 periodontal pathogens were determined in each sample using highly sensitive and specific Taqman real-time PCR assays. Data were analyzed using an ordinal regression model., Results: Significantly more total bacteria were detected in samples from the periodontitis sites of the khat chewers (OR=20). Treponema denticola was present at significantly higher absolute counts at the healthy as well as periodontitis sites of the khat chewers (OR=3.13 and 13, respectively). However, the khat chewers harbored significantly lower absolute counts of Porphyromonas gingivalis at the healthy sites (OR=0.07). Furthermore, khat chewing was significantly associated with lower relative counts of Porphyromonas gingivalis, fusobacterium ssp., prevotella ssp. and Parvimonas micra-like species in subgingival plaque samples from both healthy and periodontitis sites (OR=0.11-0.33). Only Treponema denticola was found in higher relative counts at the healthy sites of the khat chewers (OR=2.98)., Conclusions: Overall, there was a lower burden of pathogens in the khat chewers. Findings from the current study are suggestive of a potential prebiotic effect for khat on periodontal microbiota., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Within the last decade the hitherto little known psychoactive substance of khat has emerged as a regional and international issue. In the Horn of Africa khat production has spurred an economic boom, but dramatic increases in consumption have raised public health concerns. Given the complexity of the topic spanning multiple academic disciplines and fields of professional practice, the need for a systematic overview is urgent. To facilitate the exchange of information, prompt interdisciplinary research and alert international organisations and governments, the authors organised an international and interdisciplinary khat conference in 2009. This special issue of the Journal of Ethnopharmacology contains articles written by different conference speakers that present the current state of knowledge and the challenges for future research and politics., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Ethnopharmacological Relevance: Catha edulis (khat) is a plant whose fresh young leaves are used by an estimated five million people in eastern Africa and the Arabian Peninsula as a drug of recreation. The fresh leaves and shoots are rich in cathinone, a psychostimulant with effects similar to those of amphetamines. Psychostimulants produce a dose-related excitation of the central nervous system which can lead to seizures and convulsions. However there are no reports on studies of the effect of this herb on brain excitability and seizures. This knowledge is useful for doctors who may prescribe drugs whose side effects include lowering seizure threshold because there could be additive proconvulsant effect among khat users., Aim of the Study: to determined whether khat lowers pentylenetetrazole (PTZ) seizure threshold., Methodology: Male Sprague dawley rats were given fresh aqueous khat extract, old aqueous khat extract (3 g/kg bw), methylphenidate or saline and the timed intravenous (PTZ) seizure threshold test was used to study its effect on seizure threshold., Results: Fresh khat (3 g/kg) and methylphenidate (4 mg/kg) lowered PTZ seizure threshold., Conclusion: Khat lowers seizure threshold.

The potential effect of Khat (Catha edulis, Celastraceae) on fertility in humans has not been elucidated. In this study, we used the olive baboon (Papio anubis, Cercopithecidae) to determine the effects of oral administration of khat on circulating hormones. In order to establish baseline hormonal levels, five male baboons were bled once a week for 1 month. The same baboons were then fed with crude khat juice extract once a week over a period of 2 months, and the effects on serum levels of cortisol, testosterone and prolactin determined using enzyme immunoassay (EIA) and radioimmunoassay (RIA). Subsequently, sampling was repeated for a further 1 month to determine the residual effect of khat. The results showed that khat administration causes a significant increase in the mean levels of testosterone while prolactin and cortisol levels were reduced. These effects were also evident 1 month post treatment and indicate khat may exert a transient effect on male fertility by interfering with the hormonal profiles.

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 2h 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.

In this study, the effect of regular khat chewing on serum glucose and C-peptide levels were investigated in both healthy male individuals and type 2 diabetic patients. The results presented show the levels of glucose and C-peptide of healthy individuals to be non-significantly different between khat and non-khat chewers which may be due to the rapid release of insulin which prevents the sympathetic khat effect on rising serum glucose. On comparing both diabetic groups, those of khat chewers showed a non-significant increase of glucose levels at 0, 1 and 2 h of khat chewing. However, the non-significant increase of serum glucose at 1 h of khat chewing corresponded with a significant increase of serum C-peptide (22%) levels. On selecting the base-line glucose of diabetic individuals between 200 and 450 mg/dl, both diabetic khat and non-khat chewers still showed no significant difference in serum glucose and C-peptide at 2 h post-meal. However, serum glucose was seen to be significantly higher in the khat chewers by 32.1 and 32.6% after 1 and 2 h of khat chewing, respectively. Along the same line, serum C-peptide was higher in the khat chewers by 39.4 and 12.9% at 1 and 2 h of khat chewing, though not significantly. In conclusion, chronic khat chewing does not affect serum glucose and C-peptide in healthy individuals while it increases glucose and C-peptide levels during the khat session in diabetic individuals especially those having serum glucose between 200 and 450 mg/dl at 2 h post-meal.

The aim of this study was to determine if the psychostimulants, khat and amphetamine, exert similar effects in two tests of motor behaviors. Dose-response relationships were obtained for khat extract and D- and L-amphetamine given to mice by the intragastric route. Head twitch responses were significantly increased by khat and amphetamines. The latter were more potent than khat; dose-response curves for amphetamines had inverted U shapes. Khat extract decreased spontaneous motor activity, as measured by a photoactometer. Effects of amphetamines in this test were more variable and subject to dose dependent reversal. Other behaviors produced by higher doses of amphetamines interfered with specific motor responses under evaluation. Pretreatment with methysergide, a serotonin antagonist, significantly blocked head twitch responses but not spontaneous activity. Conversely, pretreatment with haloperidol decanoate, a dopamine receptor antagonist, prevented inhibition of spontaneous motor activity ordinarily evoked by khat and low dose D-amphetamine. We conclude that motor effects of khat and amphetamine resemble one another, but only at certain doses. Unlike khat, amphetamine causes additional behaviors that obscure motor responses of the types examined here. Results with transmitter receptor blockers suggest that motor effects of khat, like those of amphetamine, may be modulated by serotonin and dopamine.

Catha edulis is a plant that grows in certain areas of East Africa and the Arab Peninsula. The stimulating properties of fresh material were described more than seven centuries ago and today the habit of inducing a state of euphoria and subjective well-being by chewing Catha edulis prevails among the inhabitants of these regions. Oral administration of this plant and its active constituents (cathine and cathione) on experimental animals might have stimulating effects on adrenocortical function. This was indicated by the significant decrease in adrenal cholesterol, ascorbic acid, glycogen, and the increase in adrenal phosphorylase activity. In addition, the level of urinary 17-hydroxycorticosteroids and plasma free fatty acids were increased.

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.

Khat (Catha edulis Forsk.), known in Somalia as "qaad" or "jaad", is a plant whose leaves and stem tips are chewed for their stimulating effect. From the Harar area, khat has been introduced at different times into the present day territories of Somalia, Djibouti, South and North Yemen, Kenya, Madagascar, Tanzania and down to south eastern Africa. The plant, which belongs to the Celestraceae family, grows wild at altitudes of 1500-2000 m above sea level. Among the various compounds present in the plant (more than forty alkaloids, glycosides, tannins, terpenoids, etc.), two phenylalkylamines, namely cathine [+)-norpseudoephedrine) and cathinone [-)S-o-aminopropiophenone) seem to account mostly for the effect. The consumers get a feeling of well-being, mental alertness and excitement. The after effects are usually insomnia, numbness and lack of concentration. The excessive use of khat may create considerable problems of social, health and economic nature. These problems have been summarily reviewed. Khat chewing started at different times in different parts of Somalia. Since World War II, the prevalence of the practice has continuously increased and no social group is excluded. An epidemiological research to compare Northern and Southern regions of Somalia and to obtain a rough estimate of prevalence, definition of social characteristics of the groups of consumers, specification of the motivations, patterns of use and effects during and after consumption has been conducted. Consumers and non-consumers (7485 people) were randomly interviewed in the two regions. Khat consumption in relation to sex, age, occupation and grade of education is presented.

In order to investigate effects of khat chewing on uteroplacental blood flow, eight awake, chronically catheterized guinea pigs were fed 2.2 g khat leaves/kg in late pregnancy and regional blood flows were measured with the microsphere technique. Seven animals fed with aspen leaves in the same amounts served as controls. The mean concentration of (+)-norpseudoephedrine in urine 3 h after the end of the feeding was 4.6 micrograms/ml in the khat-fed group with no detectable amounts in the controls. Placental blood flow was reduced by 10% 75 min and by 24% 180 min after khat feeding. Since the khat dose used gave urinary concentrations of (+)-norpseudoephedrine of the same magnitude as those reported in khat chewing women, khat chewing in pregnancy may reduce placental blood flow and impair fetal growth.

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.

Rats chronically implanted with cortical screw electrodes were treated with three different oral doses of a Khat extract and the EEG recorded for 5 h. Several abnormalities in EEG patterns were observed, particularly after the administration of the largest dose (400 mg/kg). Spectral analysis of EEG showed a significant shift of frequencies towards faster, lower voltage activity following administration of the two smaller doses (50 and 100 mg/kg), reflecting a stimulant effect of the extract. The highest degree of cortical activation was observed following administration of the smallest dose. With the largest dose, an initial activation was followed by a state of EEG depression characterized by a high percentage of slow, high voltage waves. It is concluded that Khat extract in small doses has a stimulant effect on the rat brain, but with larger doses induces a state of depression.

Khat chewing is a widespread male social habit in countries around the southern shore of the Red Sea and in eastern Africa and is also practiced by women, even during pregnancy and lactation. In order to study the potentially adverse effects of khat chewing during pregnancy, guinea pigs were fed 2.2 g/kg of khat leaves daily throughout the third trimester. Control animals were given aspen leaves. Maternal daily food intake was significantly reduced during the first 10 days of feeding and maternal weight gain was slightly lower in the khat group. Khat feeding of the mother significantly reduced the mean birth weight of the offspring by 7% without any effect on litter size or length of gestational period. Since low birth weight is a well-established risk factor for both perinatal and young infant death, khat chewing during pregnancy may be one of the factors contributing to infant mortality.

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).

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.

Nor-pseudoephedrine, one of the active ingredients of khat (Catha edulis), was found to be excreted in breast-milk in several lactating women who were chewing the leaves of the shrub according to the local customs. The compound could be traced in the urine of one breast-fed infant. It is concluded that the use of khat during lactation should be discouraged until further research has clearly elucidated the potential health hazards.