A Narrative Review of the Toxic Effects on Male Reproductive and Sexual Health of Chewing the Psychostimulant, Catha edulis (Khat).

Khat (Catha edulis Forsk) is a stimulating narcotic grown mainly in East and Southern Africa. The plant has a long history as a popular social behavior within these regions, and its active ingredient, cathinone, has been thought to cause an array of physical, psychological, and mental health complications. In 1980, the World Health Organization (WHO) classified it as an illicit substance due to the potential for psychological dependence. Subsequent investigations have found that its regular consumption can negatively impact the human central nervous system (CNS), systemic blood pressure, genitourinary system, and psychological health. This narrative review aims to discuss the reproductive toxicity and sexual dysfunction (SD) caused by regular khat usage in humans and experimental animals. Animal studies found dose-dependent impacts on male reproductive health: low levels increased testosterone production, whereas high levels had the opposite effects. Moderate intake was associated with reduced luteinizing hormone (LH) levels and heightened cortisol in blood plasma. In human studies, chronic users had dramatically lower semen volume, sperm motility, and count, as well as reduced libido or erectile dysfunction (ED). Khat can have serious implications for male fertility and sexual health: therefore, better understanding of its effects is paramount. This article aims to review the toxic effects on the male reproductive and sexual health of chewing the psychostimulant, Catha edulis (khat).

Khat Chewing Effect on the International Normalized Ratio in Patients with Mechanical Heart Valves under Warfarin Therapy.

BACKGROUND AND OBJECTIVE: Khat is a plant that contains the alkaloids cathine and cathinone which have some amphetamine-like properties. It is cultivated and it's leaves chewed for their euphoric effect. This study intended to elucidate the effect of khat chewing on blood coagulation by using the International Normalized Ratio (INR) value as a calculable benchmark. MATERIALS AND METHODS: In this cohort study, 146 patients with Mechanical Heart Valves (MHV) were assessed for two consecutive visits at one-month intervals. For each visit, the date of surgery, the patient's compliance, the dose of warfarin and the INR reading were assessed by the researcher. RESULTS: Out of 146 patients with MHV, the mean age was 33.72±12.43 years (range, 14-65 years); 82 (56.2%) were female and 64 (43.8%) were male. The results revealed that the mean of absolute INR readings was lower in khat-chewers than non-chewers by average 0.2 on the first and second visits (p = 0.038 and 0.002, respectively). CONCLUSION: Khat chewing has a significant coagulant effect. There was a significant decrease in the value of INR for khat chewers patients with MHV when compared to non-khat chewers.

Prevalence of hypertension and associated factors among adult residents in Arba Minch Health and Demographic Surveillance Site, Southern Ethiopia.

Hypertension is the leading risk factor for mortality and it is also one of the major risk factors for other non-communicable diseases (NCDs). The objective of the study was to assess the prevalence of hypertension and its associated factors among adults residing in Arba Minch health and demographic surveillance site (HDSS), Southern Ethiopia. A community-based cross-sectional survey was conducted in 2017 on the estimated sample size of 3,368 adults at Arba Minch Health and Demographic Surveillance site (HDSS). Data were collected using the WHO STEPS survey tools. Bivariate analysis was done to detect candidate variables at P-value less than 0.25 and entered into the final model to identify the independent predictors of hypertension. The prevalence of hypertension was 18.92% (95% CI: 17.63-20.28). The magnitude increase among respondents in the older age group [AOR 1.39 (95%CI: 1.05-1.84), 1.68 (95% CI: 1.26-2.23) and 2.67 (95%CI: 2.01-3.56) for age group 35-44, 45-54 and 55-64, respectively, compared to 25-34 years old group] and those with the higher wealth index [AOR 1.86 (95%CI: 1.33-2.59), 2.68 (95% CI: 1.91-3.75) and 2.97 (95%CI: 2.08-4.25) for 3rd quantile, 4th quantile and 5th quantile, respectively, compared to 1st quantile]. The odds of hypertension reduce among married participants (AOR 0.66, 95%CI: 0.51-0.85). Respondents with overweight (AOR 1.44, 95%CI: 1.02-2.02), khat chewing (AOR3.31, 95%CI: 1.94-5.64), low fruit and/or vegetable consumption (AOR 1.27, 95%CI: 1.05-1.53) and those who do not use coffee and tea (AOR 1.52, 95%CI: 1.03-2.24) had significantly higher likelihood of hypertension. Nearly one out of five participants have hypertension in this population. As hypertension is one of the silent killers, it is advisable to develop a system for enabling early detection and monitoring in the older age groups and overweight individuals.

Evaluation of Khat (Catha edulis) Use as a Risk Factor of Cancer: A Systematic Review.

BACKGROUND: Conducting systematic review to evaluate plant use as a risk factor to cancer could be challenging. A systematic and well-balanced method should be applied to accommodate in vivo and in vitro studies to make a final decision. In this article, khat, a recreational plant used in some Arabic and African regions, was employed as an example to systematically determine its relationships to the premalignant and cancerous conditions. METHODS: Systematic database search was performed to recruit original human, animal or in vitro studies on khat and cancer. Sixteen studies fulfilled the inclusion criteria and subjected to assessment using Risk of Bias (RoB). Office of Health and Translation (OHAT) approach was used to rate the confidence level in the body of evidence. The evidence was integrated to establish the relationships between khat, premalignant conditions and cancer. RESULTS: Seven out of eight studies showed that khat causes premalignant oral lesions with moderate evidence level. Four studies showed that khat causes cancer with low evidence level and another three studies showed that khat has anti-cancer effect with moderate to high evidence level. Only one study suggested that khat is unrelated to cancer. CONCLUSION: RoB and OHAT approach are reliable systematic tools to evaluate plant risk to cancer and provide objective and uniform summary regardless of the study type. In conclusion, our pooled analysis did not find a direct relationship between khat and cancer but anti-cancer effect would require to be proofed on human studies.

Khat (Catha edulis Forsk) - And now there are three.

For centuries, a large number of people living in the southwestern part of the Arabian Peninsula and eastern Africa have chewed the fresh leaves and twigs of the plant Catha edulis Forsk, more commonly known as khat, for its psychostimulatory effect. The main active compound in khat is cathinone, whose synthetic derivatives form a part of the new psychoactive substances list. This review summaries the prevalence of khat use, its harvesting and consumption, the biosynthetic pathway in khat, the mechanism of action, the results from animal and human studies, and its dependence potential. It is unlikely that khat use will be prohibited in countries where it is traditionally consumed and socially acceptable unlike in other countries of the world where both the importation and the consumption of khat and cathinone is banned. Khat users being mainly Muslims prohibited from using alcohol or other drugs probably represent the largest global number of mono-drug users of an amphetamine-like stimulant. Thus, khat use represents a unique situation and a neglected area of research in Africa.

Khat: A Substance of Growing Abuse with Adverse Drug Interaction Risks.

The growing global availability of the stimulant shrub, khat, has aroused widespread concern. This paper is a review of possible adverse interactions between khat and conventional drugs. Khat chewing has been shown to reduce the bioavailabilities of orally co-administered antibiotics, ampicillin, amoxicillin, cephradine and tetracyclineHCl, and the antimalarial drug, chloroquine. The cardiovascular and central nervous system (CNS) stimulant effects of monoamine oxidase inhibitors (MAOI) and amphetamine-like drugs have been described to be enhanced by khat chewing. Khat is recognized to have the ability to counteract the effects of antihypertensive, antiarrhythmic and local anesthetic drugs, and to offset the cardioprotective action of aspirin. Depending on the amount or duration of consumption, khat has been reported to variably affect the actions of general anesthetics. Khat is likely to augment the effects and/or toxicity of different drugs due to its inhibitory action on the drug metabolizing enzyme CYP2D6. While specific mechanisms have been suggested for some of the khat-drug interactions reported, the mechanisms for other interactions are less clear. Despite the above observations, the literature reviewed is associated with a number of shortcomings, suggesting the need for further research and documentation on this area of knowledge. It is recommended that, in the interim, health care providers should be more familiar with the known and suspected adverse khat-drug interactions in order to optimally serve their patients who chew khat.

Khat (Catha edulis) and its oral health effects: An updated review.

Khat or qat (Catha edulis) is a plant that grows in East Africa and southern Arabia. The leaves and twigs of this small tree are chewed by several millions of people worldwide for their stimulating amphetamine-like effects. The reported prevalence of khat chewing in Europe and the USA is on the rise, especially with global migration. Long-term khat chewing has several detrimental general and oral health effects. The aim of the present study was to review the current literature regarding khat use and its association with oral and dental diseases, with particular emphasis on its link with oral keratotic white lesions and oral cancer. We searched the literature to identify all relevant articles. Studies showed that khat is associated with several oral and dental conditions, including keratotic white lesions, mucosal pigmentation, periodontal disease, tooth loss, plasma cell stomatitis, and xerostomia. There are limited data on the incidence of dental caries among khat chewers. The evidence that khat chewing is a risk factor for oral cancer is still weak, and is mainly based on anecdotal case reports and uncontrolled studies.

Khat-induced liver injuries: A report of two cases.

Khat is consumed for recreational purposes in many countries, including Yemen, where >50% of adults chew khat leaves regularly. A wide spectrum of khat-induced liver injuries has been reported in the literature. Herein, we report two patients with khat-induced liver injury. Both patients clinically presented with acute hepatitis, one of whom showed radiological evidence of hepatic outflow obstruction. Based on the histological tests, both patients had acute hepatitis, which indicated drug-induced liver injury (DILI) on a background of chronic hepatitis and portal fibrosis; of the two, one presented with symptoms of immune-mediated liver injury.

To chew or not to chew: that's the question.

A 25-year-old Somalian man was referred to the department of internal medicine because of nausea, vomiting and jaundice of recent onset. On physical examination, he was frankly icteric without clinical signs of chronic liver disease. Laboratory data showed evidence of acute hepatitis. Viral serologic tests for hepatitis A, B, C and E were negative. Antinuclear antibodies (ANA) were positive (titre 1 : 1280; speckled pattern, NV < 1 : 40) as well anti-actin antibodies (titre 75 UA, NV < 20). A liver biopsy was performed and showed a feature compatible with toxic hepatitis. On further questioning, the patient admitted to daily chew Khat when he was living in Somalia. We concluded to Khat-induced toxic hepatitis together with high-titre anti-nuclear antibody mimicking serologic patterns of auto-immune hepatitis.

Khat Use: What Is the Problem and What Can Be Done?

The chewing of khat leaves is an established tradition in East Africa but is much less prevalent in other areas of the world and is mostly limited to Somali communities. However, our understanding of what constitutes problematic khat use in the Somali community in Victoria, Australia, is limited. The objectives of this study were to better understand the views of Somali community representatives and primary care practitioners regarding problematic khat use, to consider relevant harm minimisation strategies, and to develop resources to assist individuals with problematic khat use and their families. Qualitative research methods were used to investigate the experiences and perceptions of khat use among Somalis and mainstream primary care practitioners. Six focus groups were conducted with 37 members of the Somali community and 11 primary care practitioners. Thematic analysis was used to analyse transcripts. Various indicators of the problematic use of khat were identified, including adverse physical and mental health effects, social isolation, family breakdown, and neglect of social responsibilities. Potential harm minimisation strategies were identified including the adoption of health promotion through education, outreach to the community, and the use of universal harm minimisation strategies specifically tailored to khat use.

Subacute administration of crude khat (Catha edulis F.) extract induces mild to moderate nephrotoxicity in rats.

BACKGROUND: Although various studies have been conducted to shed light on the pharmacological actions of khat, little or no data are available regarding khat's effect on the renal redox system. The aim of this study was therefore to investigate the potential of nephrotoxicity associated with khat exposure in rats. METHODS: Sprague Dawely rats were randomly assigned into eight experimental groups. Animals were treated with Tween80, gentamicin 100 mg/kg and khat at various doses (100, 200 and 400 mg/kg) alone or in combination with gentamicin for ten days. The animals were then sacrificed to obtain blood and renal tissues for subsequent analysis. Renal markers, including creatinine, blood urea nitrogen, antioxidant enzymes as well as markers for lipid peroxidation were determined using established protocols. In addition, histopathological changes were evaluated with hematoxilin and-eosin staining technique. RESULTS: Lower and moderate doses of khat did not alter the measured parameters compared to controls. By contrast, higher dose (400 mg/kg) of khat not only increased levels of serum creatinine and blood urea nitrogen (p < 0.001) but also levels of malondialdehyde (p < 0.01). Moreover, 400 mg/kg of khat significantly decreased enzymatic activities of superoxide dismutase (p < 0.01) and catalase (p < 0.001). When khat was administered with gentamicin, it was again the higher dose that significantly accentuated gentamicin-induced alterations in the renal system. CONCLUSIONS: Khat treatment at high dose is demonstrated to induce mild to moderate renal damage. Moreover, it creates synergy when combined with nephrotoxic drugs such as gentamicin.

Association between khat chewing and gastrointestinal disorders: a cross sectional study.

BACKGROUND: Khat (Catha edulis Forsk) is a psycho-stimulant substance grown in East Africa. But its adverse effects and its prevalence are not well studied. The main aim of the present study is thus to assess the association between khat chewing and GI problems among students in Ambo University. METHODS: A cross-sectional study was conducted in January 2010 on 1005 Ambo University students. Study subjects were selected using systematic random sampling technique, and data were collected using self-administered questionnaire. Data analysis was made using SPSS version 16.0 for windows package. RESULTS: The mean age of the respondents was 20.79 ± 1.39 ranging from 18-30 years. Seven hundred twenty (71.6 %) of the study participants were males and 994 (98.9%) were in the age group of 15-24 years. The prevalence of gastritis was 580 (57.7%); constipation 235 (23.4%); hemorrhoids 54 (5.4%) and that of dental problems (carries, decay, filling and extraction) was 225 (22.4%) of all study participants. Gastrointestinal disorders were found to be higher among khat chewers, where 64(36.2%) of them had dental problems; 127(71.8%) symptoms of gastritis; 86(48.6%) constipation and 26(14.7%) hemorrhoids which demonstrated statistically significant association with p < 0.001. CONCLUSION: The prevalence of gastrointestinal disorders was found to be higher among khat chewers, indicating that khat chewing could be a predisposing factor to gastrointestinal disorders. Community-based awareness creation about the adverse effect of khat use is thus recommended.

Khat dependence syndrome: a cross sectional preliminary evaluation amongst UK-resident Yemeni khat chewers.

ETHNOPHARMACOLOGICAL RELEVANCE: Khat is a natural psychostimulant that has pharmacological effects similar to that of amphetamine. The behaviour of khat chewing is embedded within a cultural context. Meanwhile khat chewing is associated with psychological and physiologically burden, as a 'dependence producing' substance. AIMS OF THE STUDY: To assess the applicability of the construct of substance dependence syndrome (DSM-IV, 1994) to khat chewing and to examine psychosocial and behavioural correlates of this syndrome including tobacco use. MATERIALS AND METHODS: A sample of 204 khat chewers was recruited during random visits to khat sale outlets. A face to face interview that assessed socio-demographic, psychosocial dependence, substance dependence syndrome and behavioural characteristics was conducted. Descriptive, exploratory psychometric and multivariate analyses were employed. RESULTS: Approximately a third (31%) of khat chewers reported symptoms consistent with dependence syndrome including increased khat chewing (13%) and cessation attempts (19%) while 17% reported withdrawal symptoms including depression (61%), increase in appetite (74%) and interrupted sleep (58%). Thirty-eight percent reported continued khat chewing despite impacts on their health. Psychometric assessment of the DSM-IV criteria for khat chewing dependence identified two factors; factor 1 consisted of bio-behavioural items and factor 2 withdrawal items, accounting for 67% of the variance and Cronbach's alpha coefficient at 0.78. In multivariate logistic regression modelling, there was an association between intensity of psychological khat dependence (SDS-Khat) and nicotine dependence with the likelihood of exhibiting khat chewing dependence syndrome (p=0.0005, OR=1.51, 95%CI=1.33-1.71; p=0.043, OR=2.87, 95%CI=1.03-7.98, respectively). CONCLUSIONS: The substance dependence syndrome criteria are applicable to khat chewing and associated with increased intensity of nicotine and psychological khat dependence. The applicability of khat dependence syndrome and exploration of its dimensions and associated factors should be extended in future research. Concurrent validation of these findings using specific objective measures for self-report khat chewing is also recommended.

Khat use is associated with increased response conflict in humans.

OBJECTIVE: Khat consumption has become a worldwide phenomenon broadening from Eastern Africa and the south west of the Arabian Peninsula to ethnic communities in the rest of the world. Only few studies have systematically looked into cognitive impairments in khat users. We studied whether khat use is associated with changes in the emergence and resolution of response conflict, a central cognitive control function. METHOD: Khat users (n = 16) and khat-free controls (n = 16) were matched in terms of sex, ethnicity, socio-economical situation, age, alcohol and cannabis consumption, and IQ (Raven's Progressive Matrices). Groups were tested on response conflict, as measured by the Simon task. RESULTS: Khat users performed significantly slower than controls and were more strongly affected by stimulus-induced response conflict. CONCLUSIONS: Khat use is associated with specific impairments in behavioral control: general slowing and less efficient resolution of response conflicts, which is likely to impair decision making in everyday life.

Validation of self-reported khat chewing amongst khat chewers: an exploratory study.

ETHNOPHARMACOLOGICAL RELEVANCE: Khat chewing amongst the UK communities originating from Yemen and the East African coast is suggested to create dependency through its main stimulant components (cathinone, norephedrine and norpseudoephedrine) on the central nervous system. AIMS OF THE STUDY: To validate self-reported khat chewing behaviours by measuring levels of cathinone, norephedrine and norpseudoephedrine in saliva and to explore their associations with self-reported khat chewing dependency. MATERIALS AND METHODS: Face-to-face interviews were conducted amongst 30 male UK-resident khat chewers. Saliva samples were collected from each participant and high-performance liquid chromatography (HPLC) employed to extract and quantify the levels of the biomarkers. RESULTS: The mean (SD) for cathinone and the composite norephedrine and norpseudoephedrine levels were 33.93 (±39.20) and 29.28 (±26.32)µg/mL respectively. These biomarkers were significantly associated (p≤0.05) with khat chewing dependency. CONCLUSIONS: Validation of self-reported khat chewing is possible. Khat chewing dependency correlates significantly with biomarker levels in saliva. Replication is required.

Acute coronary syndrome and khat herbal amphetamine use: an observational report.

BACKGROUND: The khat plant is a stimulant similar to amphetamine and is thought to induce coronary artery spasm. Khat is widely chewed by individuals originating from the Horn of Africa and the Arabian Peninsula. The aim of this study was to evaluate the clinical characteristics and outcome of khat chewers presenting with acute coronary syndrome. METHODS AND RESULTS: From October 1, 2008, through June, 30, 2009, 7399 consecutive patients with acute coronary syndrome were enrolled in the Second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Nineteen percent of patients were khat chewers; 81% were not. Khat chewers were older, more often male, and less likely to have cardiovascular risk factors. Khat chewers were less likely to have a history of coronary artery disease and more likely to present late and to have higher heart rate and advanced Killip class on admission. Khat chewers were more likely to present with ST-segment-elevation myocardial infarction. Overall, khat chewers had higher risk of death, recurrent myocardial ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared with non-khat chewers. After adjustment for baseline variability, khat chewing was found to be an independent risk factor of death and for recurrent ischemia, heart failure, and stroke. CONCLUSIONS: Our data confirm earlier observations of worse in-hospital outcome among acute coronary syndrome patients who chew khat. This worse outcome persists up to 1 year from the index event. This observational report underscores the importance of improving education concerning the cardiovascular risks of khat chewing.

The health impacts of khat: a qualitative study among Somali-Australians.

OBJECTIVES: To identify patterns of khat use among Somali-Australians in Australia and to explore their views about the links between khat use and personal health. DESIGN, SETTING AND PARTICIPANTS: Qualitative study using semistructured focus groups among adult members of Somali communities in Brisbane, Sydney, Melbourne and Perth who volunteered to attend focus groups in January and December 2010. MAIN OUTCOME MEASURES: Emergent themes related to Somali-Australians' understanding of the links between khat use and personal health. RESULTS: Nineteen focus groups included 114 participants. Khat use was reported to be common among the Somali community, and more common among men than women. Khat was usually chewed in prolonged sessions, producing mild psychostimulant effects such as increased energy, enhanced mood, reduced appetite and reduced sleep. Khat was widely perceived to be a food, not a drug, and as harmless, or even beneficial, to the user's health. Many users reported discontinuation effects such as lethargy, sleep disturbances and mood problems after sessions of heavy khat use, and some reported self-medicating with alcohol to cope with such problems. Problems of addiction to khat were identified by some participants, but not all believed it is addictive. Many khat users reported visiting their health professionals for treatment of adverse effects and failing to disclose their khat use. CONCLUSIONS: Health professionals require greater awareness of khat use and related health problems. Health promotion activities targeting communities with high levels of khat use are required to increase understanding of the potential risks of regular khat use, to promote harm-reduction strategies, and to increase awareness of services available for those experiencing harm. Health professionals should consider targeted screening for khat use among individuals from Horn of Africa communities who present to health services.