(1/40) Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves.
AIM: The stimulating herbal drug khat is habitually used in East Africa and the Arabian peninsula but is also imported into other countries. The aim was to study the pharmacokinetics of its alkaloids cathinone, cathine and norephedrine. METHODS: Four volunteers chewed khat leaves in an amount equivalent to one-quarter of that used in a typical khat session. Blood samples were collected up to 80 h and the alkaloids were assayed using gas chromatography-mass spectrometry. The data were evaluated using computerized pharmacokinetic compartmental analysis. RESULTS: The plasma concentration-time data for the alkaloids could be described using a two-compartment model with two-segment absorption. The mucosa of the oral cavity is considered to be the first absorption segment, where the major proportion of the alkaloids is absorbed (mean +/- SD 59 +/- 21% for cathinone and 84 +/- 6% for cathine). The extraction of the alkaloids from the leaves by chewing was very effective with only 9.1 +/- 4.2% remaining as a residue. Cathinone was eliminated from the central compartment with a mean half-life of 1.5 +/- 0.8 h. The half-life of cathine was 5.2 +/- 3.4 h. The metabolism of cathinone to norephedrine had a substantial influence on its plasma concentration profile. Psychophysical functions were essentially unaffected by the chewing of khat. CONCLUSIONS: The pharmacokinetics of khat alkaloids in humans explain why chewing is the preferred form of khat ingestion. Subjects absorbed a mean dose of 45 mg of cathinone, and did not suffer any severe adverse reactions. (+info)
(2/40) Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.
Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC(50)) for khat (200 microg ml(-1))-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 x 10(-7) M as compared to 2 x 10(-8) M and 8 x 10(-8) M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8. (+info)
(3/40) Khat habit and its health effect. A natural amphetamine.
Chewing the leaves of the khat shrub is common in certain countries of East Africa and Arabian Peninsula mainly Yemen. It has been established that a khat plant leaves contain an active psycho-stimulant substance known as cathinone that is similar in structure and pharmacological activity to amphetamine in affecting the CNS. Intoxication with khat is self-limiting but chronic consumption can cause certain health disturbances in the user and also lead to social and economic damage to the individual and the community. In recent years, several cases of intoxication have been observed outside the area of its use. In this view, the khat habit, its health effects and socioeconomic aspects are described with the political issue they imply. (+info)
(4/40) Khat use as risk factor for psychotic disorders: a cross-sectional and case-control study in Somalia.
BACKGROUND: Little is known about the prevalence of khat-induced psychotic disorders in East African countries, where the chewing of khat leaves is common. Its main psycho-active component cathinone produces effects similar to those of amphetamine. We aimed to explore the prevalence of psychotic disorders among the general population and the association between khat use and psychotic symptoms. METHODS: In an epidemiological household assessment in the city of Hargeisa, North-West Somalia, trained local interviewers screened 4,854 randomly selected persons from among the general population for disability due to severe mental problems. The identified cases were interviewed based on a structured interview and compared to healthy matched controls. Psychotic symptoms were assessed using the items of the WHO Composite International Diagnostic Interview and quantified with the Positive and Negative Symptoms Scale. Statistical testing included Student's t-test and ANOVA. RESULTS: Local interviewers found that rates of severe disability due to mental disorders were 8.4% among males (above the age of 12) and differed according to war experiences (no war experience: 3.2%; civilian war survivors: 8.0%; ex-combatants: 15.9%). The clinical interview verified that in 83% of positive screening cases psychotic symptoms were the most prominent manifestations of psychiatric illness. On average, cases with psychotic symptoms had started to use khat earlier in life than matched controls and had been using khat 8.6 years before positive symptoms emerged. In most cases with psychotic symptoms, a pattern of binge use (> two 'bundles' per day) preceded the onset of psychotic symptoms, in contrast to controls of the same age. We found significant correlations between variables of khat consumption and clinical scales (0.35 to 0.50; p < 0.05), and between the age of onset of khat chewing and symptom onset (0.70; p <0.001). CONCLUSION: Evidence indicates a relationship between the consumption of khat and the onset of psychotic symptoms among the male population, whereby not the khat intake per se but rather early onset and excessive khat chewing seemed to be related to psychotic symptoms. The khat problem must be addressed by means other than prohibition, given the widespread use and its role in Somali culture. (+info)
(5/40) Khat chewing is a risk factor for acute myocardial infarction: a case-control study.
AIM: Khat chewing is a common habit in Yemen and east African countries. Millions of people chew khat leaves daily for its euphoric and energetic effects and to increase alertness. Cathinone, the main active substance in fresh khat leaves, has sympathomimetic effects which increase heart rate and blood pressure. The aim was to examine the hypothesis that khat chewing is a risk factor for acute myocardial infarction (AMI) using a hospital-based matched case-control study. METHOD: Between 1997 and 1999, we selected 100 patients admitted to the Al-Thawra teaching hospital Sana'a ICU, Yemen with acute myocardial infarction. 100 control subjects, matched to cases for sex and age, were recruited from the outpatients clinics of the same hospital. A questionnaire was completed for case and control groups covering personal history of khat chewing, smoking, hypertension, diabetes and any family history of myocardial infarction. A blood sample was collected for performing lipid profiles. Cases and controls were compared by analysis conducted using conditional logistic regression which corrected for baseline imbalances leading to less biased estimations of odds ratio (OR). The risk associated with each classical factor and khat chewing habits was then investigated. OR values greater than 2.5 indicated a significant risk factor. RESULTS: Khat chewing was significantly higher among the AMI case group than control group (OR = 5.0, 95% CI 1.9-13.1). A dose-response relationship was observed, the heavy khat chewers having a 39-fold increased risk of AMI. CONCLUSION: This study indicates that khat chewing is associated with AMI and is an independent dose-related risk factor for the development of myocardial infarction. (+info)
(6/40) Khat and alcohol use and risky sex behaviour among in-school and out-of-school youth in Ethiopia.
BACKGROUND: Khat (an evergreen plant with amphetamine-like properties) and alcohol are widely consumed among the youth of Ethiopia. However, their relationship to risky sexual behaviour is not well described. This study was conducted to describe the magnitude of risky sexual behaviour (unprotected sex and early initiation of sexual activity) and its association with Khat and alcohol consumption in Ethiopian youths. METHODS: A probabilistic national sample of 20,434 in-school and out-of-school youths aged between 15 and 24 years of age was selected and interviewed regarding their sexual behavior and substance use. RESULTS: Over 20% of out-of-school youth had unprotected sex during the 12-month period prior to interview compared to 1.4% of in-school youth. Daily Khat intake was also associated with unprotected sex: adjusted OR (95% CI) = 2.26 (1.92, 2.67). There was a significant and linear association between alcohol intake and unprotected sex, with those using alcohol daily having a three fold increased odds compared to those not using it: adj. OR (95% CI) = 3.05 (2.38, 3.91). Use of substances other than Khat was not associated with unprotected sex, but was associated with initiation of sexual activity: adj. OR (95% CI) = 2.54 (1.84, 3.51). CONCLUSION: A substantial proportion of out-of-school youth engage in risky sex. The use of Khat and alcohol and other substances is significantly and independently associated with risky sexual behaviour among Ethiopian youths. (+info)
(7/40) Qat habit in Yemen society: a causative factor for oral periodontal diseases.
The effect of a common habit among Yemeni population on the periodontal status was investigated. This cross-sectional study was done on 2500 Yemenis with mean age 27.01 years (1818 males and 682 females). Among these 1528 were qat chewers and 972 were non-chewers. Detailed questionnaire and pre-designed scoring system for the periodontal status were employed for each case. Study results indicated that out of 972 non-chewers 116(12%) had periodontal pocketing and 18 (1.9%) cases had gingival recession. On the other hand, out of 1528 chewers, 468 (31.8%) had periodontal pockets and 98 (6.4%) with gum bleeding, p<0.05. These effects were found to increase with increased frequency and duration of chewing. It was concluded that habit of qat can cause damage to the periodontal ligament as pocketing and gum recession. (+info)
(8/40) The consumption of khat and other drugs in Somali combatants: a cross-sectional study.
BACKGROUND: For more than a decade, most parts of Somalia have not been under the control of any type of government. This "failure of state" is complete in the central and southern regions and most apparent in Mogadishu, which had been for a long period in the hands of warlords deploying their private militias in a battle for resources. In contrast, the northern part of Somalia has had relatively stable control under regional administrations, which are, however, not internationally recognized. The present study provides information about drug abuse among active security personnel and militia with an emphasis on regional differences in relation to the lack of central governmental control-to our knowledge the first account on this topic. METHODS AND FINDINGS: Trained local interviewers conducted a total of 8,723 interviews of armed personnel in seven convenience samples in different regions of Somalia; 587 (6.3%) respondents discontinued the interview and 12 (0.001%) were excluded for other reasons. We assessed basic sociodemographic information, self-reported khat use, and how respondents perceived the use of khat, cannabis (which includes both hashish and marijuana), psychoactive tablets (e.g., benzodiazepines), alcohol, solvents, and hemp seeds in their units. The cautious interpretation of our data suggest that sociodemographic characteristics and drug use among military personnel differ substantially between northern and southern/central Somalia. In total, 36.4% (99% confidence interval [CI] 19.3%-57.7%) of respondents reported khat use in the week before the interview, whereas in some regions of southern/central Somalia khat use, especially excessive use, was reported more frequently. Self-reported khat use differed substantially from the perceived use in units. According to the perception of respondents, the most frequent form of drug use is khat chewing (on average, 70.1% in previous week, 99% CI 63.6%-76.5%), followed by smoking cannabis (10.7%, 99% CI 0%-30.4%), ingesting psychoactive tablets (8.5%, 99% CI 0%-24.4%), drinking alcohol (5.3%, 99% CI 0%-13.8%), inhaling solvents (1.8%, 99% CI 0%-5.1%), and eating hemp seeds (0.6%, 99% CI 0%-2.0%). Perceived use of khat differs little between northern and southern Somalia, but perceived use of other drugs reaches alarmingly high levels in some regions of the south, especially related to smoking cannabis and using psychoactive tablets. CONCLUSIONS: Our data suggest that drug use has quantitatively and qualitatively changed over the course of conflicts in southern Somalia, as current patterns are in contrast to traditional use. Although future studies using random sampling methods need to confirm our results, we hypothesize that drug-related problems of armed staff and other vulnerable groups in southern Somalia has reached proportions formerly unknown to the country, especially as we believe that any biases in our data would lead to an underestimation of actual drug use. We recommend that future disarmament, demobilization, and reintegration (DDR) programs need to be prepared to deal with significant drug-related problems in Somalia. (+info)