Apparent Khat chewers exposure to DDT in Ethiopia and its potential toxic effects: A scoping review.

Dichlorodiphenyltrichloroethane (DDT) is an insecticide, a member of dirty dozen persistent organic pollutants, used widely in the world until it was banned in the 1970s.The banning of DDT was strengthened by the Stockholm Convention in 2001. DDT is allowed only for malaria control in Ethiopia. However, farmers are misusing DDT and applying it to Khat (Catha edulis) farming. So, this review analyzes available data in the literature on the current trend, application, occurrence, fate and effects of DDT and its metabolites, dichlorodiphenyldichloroethane (DDD), dichlorodiphenyldichloroethylene (DDE), in the chewable parts of Khat. Generally, the concentration level of DDT, DDD, and DDE, designated as DDTs, is detected in different farmlands of Ethiopia. Some of the DDTs concentrations detected are very high (141.2-973 µg/kg (Gelemso), 194.4-999 µg/kg (Aseno) and 6253-8413.3 µg/kg (Gurage), and these concentrations may indicate increasing recent unmonitored application of DDT on Khat leaves. Some of the detected concentrations of DDT in the literature were above the maximum residue limit (MRL) set by FAO/WHO (100 µg/kg) and the European Commission 10 µg/kg in vegetables and 50 µg/kg in cereals. DDT exposure of Khat chewers linked to the concentration of DDT on Khat leaves and the amount of Khat consumed. DDT might pose health risks to chewers due to chronic toxicity, bioaccumulation, persistent and endocrine disruption properties.

Cathine and cathinone disposition kinetics and neurotransmitter profile in several organs of rats exposed to a single dose of Catha edulis (Vahl) Forssk. ex Endl. extract.

OBJECTIVES: Catha edulis (Vahl) Forssk. ex Endl. (Khat) is a stimulant plant that contains cathine and cathinone, which its abuses induce euphoria, alertness, and motor activity. Since the toxicokinetics of these substances remain unclear, this study was carried out to investigate the disposition kinetics of cathine and cathinone, the neurotransmitter profile, following a single dose of C. edulis extract in rats. METHODS: Twenty-four adult male Wistar albino rats (250-300 g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000 mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24 h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method. RESULTS: The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5 h. The concentrations peaked in the brain 2.5 h later, indicating that the heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68 and 5.07 h, respectively) and may remain in the brain for longer durations (3.31 and 2.31 h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner. CONCLUSIONS: Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest Cmax in the lung and Tmax in the heart tissues but not in the brain. In addition, neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin were differentially detected in all tested samples in a organ-specific fashion. More study is needed to identify cathine and cathinone's effects on neurotransmitter profiles. Nevertheless, these findings provided a further basis for experimental, clinical, and forensic investigations.

Effects of Catha Edulis Forsk on spatial learning, memory and correlation with serum electrolytes in wild-type male white albino rats.

BACKGROUND: The burdens of psychostimulant use disorders are becoming a worldwide problem. One of the psychostimulants widely consumed in Ethiopia and East African countries is Catha edulis Forsk (khat). However, no studies have been conducted on the cognitive effects of khat and its correlation with serum electrolytes. The present study was aimed to evaluate the effects of khat on spatial learning and memory and their correlation with serum electrolytes. MATERIALS AND METHODS: Diethyl ether and chloroform (3:1v/v ratio) were solvents used to obtain the crude khat extract in this study. T80W was used to prepare the khat juice, fresh khat leave extract. The rats were received crude khat extract subchronically (KESC) (100 mg/kg, 200 mg/kg and 300 mg/kg b.w), khat juice (KHJ 2.5 mL/kg), 2% tween 80 in distilled water (T80W- v/v, vehicle) and khat extract subacutely (KESA) (300 mg/kg). For subchronic treatment, each rat was administered for twelve weeks before Morris water maze experiment has been started, while it was administered for a week for acute treatment. Spatial learning and memory were measured using the Morris water maze model and serum sodium, calcium, potassium, and chloride were evaluated using Cobas 6000. RESULTS: Spatial learning was improved with trials across the groups, while average escape latency (s) of rats received KESC 200 mg/kg (p<0.001), KESC 300 mg/kg (p<0.01) and KHJ 2.5 mL/kg (p<0.05) was significantly greater than rats that received vehicle. There was no significant difference in the latency between rats that received KESA 300mg/kg and vehicle (p>0.05). Thigmotaxis was significantly higher in rats that received all doses of khat extract (p<0.001). The time spent in the target quadrant in rats that received KESC 300 mg/kg was significantly reduced (p<0.05). Serum calcium level was inversely correlated with the escape latency (R = -0.417, p<0.05) in rats that received khat. CONCLUSIONS: Khat extract and juice administered subchronically, but not subacutely, impaired learning and memory and was associated with serum calcium reduction. The neuronal basis for such alteration should be investigated.

Habitual khat chewing alters urinary inorganic profile in adult healthy males.

OBJECTIVES: Khat (Catha edulis) is a stimulant plant, and it is abusive to induce euphoria, alertness and activity. Concomitant use of medications and khat chewing predisposes to the appearance of drug interactions result in treatment failure or toxicity. This study determined the changes in the urinary inorganic profile in adult healthy males who are chewing khat compared with non-khat chewer males. METHODS: A total of 40 adult non-smoker healthy males (20 khat chewer and 20 non-khat chewer) aged 24-30 years were selected. Khat chewer samples were positive for cathinone and cathine and negative for other drug of abuse, while non-khat chewer samples were negative for drug of abuse include cathinone and cathine. Samples were selected according to their results in immunoassay and gas chromatography mass spectrometry (GCMS) analysis. Cathine and cathinone were confirmed using liquid chromatography mass spectrometry (LC-MSMS) analysis. Inorganic profile includes titanium (Ti), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) were determined by using inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: The levels of Ti, Co, Zn, Cd, and Pb in urine were significantly higher among the khat chewer group compared with non-khat chewer. Ti, Cd, Co, Pb and Zn urine levels were 0.5-, 1.5-, 1.15-, 5-, and 8.2-fold higher in the khat chewer group compared to non-khat chewer, respectively. CONCLUSIONS: We suggested that continuous khat chewing has a long term effect on metabolic pathway of therapeutic drugs that result in toxicity or failure of therapy.

Effect of Biochar and Inorganic Fertilizer on the Soil Properties and Growth and Yield of Onion (Allium cepa) in Tropical Ethiopia.

Biochar is a carbon-rich product, which is processed by pyrolyzing biomass to improve soil properties and maintain environmental sustainability. This study aim was to investigate the effect of biochar and inorganic fertilizer on soil properties, growth, and yield. Four treatments and four replications have been used for the experimental plots using Randomized Complete Block Design (RCBD). Soil physiochemical properties have been investigated based on soil samples within 0-30 cm depth in each plot. The two types of biochar (grass and chat waste) have been used for the treatments. The pyrolyzing temperature required for grass and chat waste is 250°C and 1100°C, respectively. The plant height, total yield, and the marketable and nonmarketable yield of onion have been examined. The analysis showed that treatment with grass biochar and inorganic fertilizer had a similar effect on soil properties but chat (Catha edulis) biochar had a lower effect on soil properties. The total yield and days to 70% maturity have been increased due to the cumulative treatment of grass biochar and inorganic fertilizer. The biochar of grass and inorganic fertilizer have been significantly increased in marketable bulb yield, but unmarketable yield becomes decreased. The chat waste and controlled treatments shown an increased unmarketable yield and declined marketable bulb yield. Overall, biochar can substitute the inorganic fertilizer, which can help to improve the w soil fertility and environmental sustainability. Therefore, biochar has a win-win solution.

Toxic Effect of Khat in Rat Embryos and Fetuses.

Khat (Catha edulis Forsk) is a plant consumed by many people in Eastern Africa, including Ethiopia, and Southern Arabia to be stimulated. There are several human and animal studies on khat that provide information about its toxic effects. However, the potential toxic effects of khat on embryos and fetuses have not been elucidated. The aim of the present study was to investigate the embryotoxic and fetotoxic effects of khat exposure during the earliest period of gestation in rats. Pregnant Wistar albino rats were treated with khat extract at 250, 500, and 750 mg/kg doses from day 6 through day 12 of gestation. The treatment was delivered by gavage. Embryos and fetuses were recovered on gestational day 12 or day 20, respectively, and were quantitatively and qualitatively assessed for developmental anomalies. Placentae from the treatment and control groups were investigated for histopathological effects. Results of the present study showed that khat exposure during pregnancy had dose-dependent toxic effects in rat embryos and fetuses. Prenatal growth retardation such as reduced fetal weight and crown-rump length was observed in near-term fetuses, especially, in animals treated with the highest dose of khat (p < 0.05). Growth retardation and developmental anomalies were also observed in day 12 embryos of khat-treated rats. Maternal weight gain of the khat-treated group was also significantly lower than the control group. Cytolysis, decidual hypoplasia, and atrophy were observed in the placenta of the khat-treated rats. Findings of the present study revealed, for the first time, that exposure of pregnant rat to crude extract of khat causes embryotoxic and fetotoxic effects.

The impact of catha edulis (vahl) forssk. ex endl. (celestraceae) (khat) on pharmacokinetics of clinically used drugs.

INTRODUCTION: Catha edulis (Vahl) Forssk. ex Endl. (Celestraceae) is used as a recreational drug on daily basis for its euphoric and psychostimulant effects. It is also chewed by individuals who are on medications, raising the possibility of drug-khat interaction. However, limited data are available in the literature, although clinically significant interactions are expected, as khat contains a complex mixture of pharmacologically active constituents. AREAS COVERED: It provides an overview of the phytochemistry, pharmacokinetics, pharmacodynamics, and pharmacogenetics of khat based on the literature mined from PubMed, Google Scholar, and Cochrane databases. It also presents a detailed account of drug-khat interactions with specific examples and their clinical significance. The interactions mainly occur at the pharmacokinetics level and particular attention is paid for the phases of absorption and cytochrome P450 enzyme-mediated metabolism. EXPERT OPINION: Despite the increasing trend of khat chewing with medications among the populace and the potential risk for the occurrence of clinically significant interactions, there is paucity of data in the literature demonstrating the magnitude of the risk. The available data, however, clearly demonstrate that the consequence of drug-khat interaction is dependent on genotype. Genotyping, where feasible, could be used to improve clinical outcome and minimize adverse reactions.

An updated review on synthetic cathinones.

Cathinone, the main psychoactive compound found in the plant Catha edulis Forsk. (khat), is a ß-keto analogue of amphetamine, sharing not only the phenethylamine structure, but also the amphetamine-like stimulant effects. Synthetic cathinones are derivatives of the naturally occurring cathinone that largely entered the recreational drug market at the end of 2000s. The former "legal status", impressive marketing strategies and their commercial availability, either in the so-called "smartshops" or via the Internet, prompted their large spread, contributing to their increasing popularity in the following years. As their popularity increased, the risks posed for public health became clear, with several reports of intoxications and deaths involving these substances appearing both in the social media and scientific literature. The regulatory measures introduced thereafter to halt these trending drugs of abuse have proved to be of low impact, as a continuous emergence of new non-controlled derivatives keep appearing to replace those prohibited. Users resort to synthetic cathinones due to their psychostimulant properties but are often unaware of the dangers they may incur when using these substances. Therefore, studies aimed at unveiling the pharmacological and toxicological properties of these substances are imperative, as they will provide increased expertise to the clinicians that face this problem on a daily basis. The present work provides a comprehensive review on history and legal status, chemistry, pharmacokinetics, pharmacodynamics, adverse effects and lethality in humans, as well as on the current knowledge of the neurotoxic mechanisms of synthetic cathinones.

Pesticide Residue Analysis of Khat Leaves and Health Risks among Khat Chewers in the Amhara Region, Northwestern Ethiopia.

Introduction: Farmers use a large number of pesticides to increase the productivity of Khat cultivation. Since Khat is consumed by many Ethiopians as a habit, there may be a significant concentration of pesticide residues in Khat leaves which result in adverse effects among the exposed population. Excess use of pesticides in Khat causes cancer, genotoxicity, and endocrine disturbances. The current study aimed to determine the concentration of selected pesticide residues on Khat leaves samples and to estimate the possible health risk on consumers. Methods: Thirty Khat samples were collected from Khat cultivators in the Amhara region, Ethiopia. Pesticide residue extraction and cleanup of Khat samples were performed using the QuEChERS method. Data were also collected about personal variables and Khat consumption habits. The pesticide concentrations were determined and the health risks were estimated. Results: Profenofos, dimethoate, and chlorpyrifos were detected in 6 (20%), 24 (80%), and 28 (93.3%) Khat samples, respectively. However, diazinon was detected in two samples and endosulfan I was not detected. The average concentration of chlorpyrifos, dimethoate, profenofos, and diazinon in Khat samples was 75.39 ± 20.26, 130 ± 48.94, 242.45 ± 119.79, and 81.5 ± 21.0 µg/kg, respectively. The HQ for diazinon was greater than 1 which shows the chronic health risks associated with intake of diazinon among Khat chewers. The acute health risks associated with intake of profenofos and diazinon were minimal. Discussion. Pesticide residue exposure is a risk factor for cardiac complications, reduction in antioxidant defense system, and developing neurological symptoms. All the pesticides were higher than the European Union Maximum Residue Levels (EU-MRL). Diazinon has the potential to cause higher chronic health risks. Chronic Khat chewers in the region may face potential health risks from pesticide residues. Awareness creation among people in the study area is necessary to avoid the adverse health effects of pesticide residues.

Valorization of khat (Catha edulis) waste for the production of cellulose fibers and nanocrystals.

Cellulose fibers (C40 and C80) were extracted from khat (Catha edulis) waste (KW) with chlorine-free process using 40% formic acid/40% acetic acid (C40), and 80% formic acid/80% acetic acid (C80) at the pretreatment stage, followed by further delignification and bleaching stages. Cellulose nanocrystals (CNCs40 and CNCs80) were then isolated from C40 and C80 with sulfuric acid hydrolysis, respectively. Thus, the current study aims to isolate cellulose fibers and CNCs from KW as alternative source. The KW, cellulose fibers, and CNCs were investigated for yield, chemical composition, functionality, crystallinity, morphology, and thermal stability. CNCs were also evaluated for colloidal stability, particle size, and their influence on in vitro diclofenac sodium release from gel formulations preliminarily. The FTIR spectra analysis showed the removal of most hemicellulose and lignin from the cellulose fibers. The XRD results indicated that chemical pretreatments and acid hydrolysis significantly increased the crystallinity of cellulose fibers and CNCs. The cellulose fibers and CNCs exhibited Cellulose Iß crystalline lattice. TEM analysis revealed formation of needle-shaped nanoscale rods (length: 101.55-162.96 nm; aspect ratio: 12.84-22.73). The hydrodynamic size, polydispersity index, and zeta potential of the CNCS ranged from 222.8-362.8 nm; 0.297-0.461, and -45.7 to -75.3 mV, respectively. CNCs40 exhibited superior properties to CNCs80 in terms of aspect ratio, and colloidal and thermal stability. Gel formulations containing high proportion of CNCs sustained diclofenac sodium release (< 50%/cm2) over 12 h. This study suggests that cellulose fibers and nanocrystals can be successfully obtained from abundant and unexploited source, KW for value-added industrial applications.

Khat Chewing and Lipid Profile in Human and Experimental Animals.

BACKGROUND: Catha edulis, also known as khat or qat, is a plant that grows in East Africa and southern Arabia. Several millions of people chew the leaves and twigs of khat plant for their central stimulating amphetamine-like effects. Khat chewing is becoming more common in Europe and the United States, owing to worldwide migration. OBJECTIVE: This review examines the khat ingredients, global prevalence, and legal status as well as its effects on lipid profile. Methodology. A literature search was performed using PubMed, Scopus, and Google Scholar to collect information within articles published up to April 2021 with the goal of identifying relevant studies. The proposed mechanisms of cathinone effects on total cholesterol and triglyceride were also discussed. CONCLUSION: The khat chewing habit is considered as a serious economic and health issue that needs specialized programs to assist those people to quit or reducing this habit.

Exploring the Molecular Mechanisms of 17ß-HSD5-induced Carcinogenicity of Catha edulis via Molecular Modeling Approach.

BACKGROUND: The tradition of khat chewing has been deep-rooted in the African and Arabian Peninsula for centuries. Due to its amphetamine-like psycho-stimulant or euphoric effect, khat has been used by millions in Somalia, Ethiopia, Saudi Arabia and Yemen. The long-term use of khat can induce many major health outcomes, which may be serious and irreversible. OBJECTIVE: Prolonged use of khat constituents has been associated with different types of cancers such as prostatic, breast and ovarian cancer. However, it has been very difficult to identify the molecular targets involved in khat carcinogenesis that interact with the Khat constituents by in vitro/in vivo experimental tools. METHODS: In silico tools were used to predict potential targets involved in the carcinogenesis of khat. Pass on-line prediction server was used for the prediction of a potential molecular target for khat constituents. Molecular Dynamics simulation and MM-GBSA calculation of the predicted target were carried out. RESULTS: Molecular Dynamics simulation and MM-GBSA calculation revealed that among khat constituents, ß-sitosterol showed a high binding affinity towards 17ß-HSD5. On the other hand, this study highlights for the first time some new interactions, which were observed in the case of cathine, cathinone and nerol during the simulation. CONCLUSION: In silico molecular dynamic simulation tools were used for the first time to investigate the molecular mechanism of widely used leaves of psychoactive khat (Catha edulis) constituent. The present study provides deep insight to understand the effect of khat constituents involved in the impairment of the reproductive system and its binding to 17ß-HSD5. ADMET profiling also suggested that few khat constituents do not fulfill the requirements of the Lipinski rule of five i.e. poor absorption and blood-brain barrier impermeability.

Determination of cathinone and cathine in Khat plant material by LC-MS/MS: Fresh vs. dried leaves.

The consumption of Khat leaves represents an ancient kind of drug abuse mainly observed in Eastern Africa and the Arab Peninsula among adult men. For this purpose, the leaves are directly collected from the shrub "Catha edulis" prior to extensive chewing process. Seizures in Europe are rare, since the leaves have to undergo quick transportation: After a short period of time, the harvested leaves decompose and suffer in decrease of concentration of the active ingredient cathinone, which makes long term transportation difficult. As an alternative, plant material can be dried to increase life period. In the past years, an increasing number of seizures were made by Austrian police, however, the content of cathinone and cathine in dry material is widely unknown. In this work, a seizure of fresh Khat leaves was compared with two seizures of dried material in terms of concentration of cathinone and cathine using LC-MS/MS analysis. For fresh leaves, a purity grade was found to be 0.115-0.158% for cathinone and 0.172-0.192% for cathine, respectively. In contrast, subsequent storage of dried Khat leaves over months led to a dramatic loss of cathinone: Analysis of two seizures revealed that concentration of cathinone dropped to 0.021-0.023%. These findings are intended to serve as a guideline for Justice authorities to estimate the content of the controlled ingredients of Khat leaves in future.

Magnitude and predictors of khat use among patients with tuberculosis in Southwest Ethiopia: A longitudinal study.

INTRODUCTION: Tuberculosis (TB) is a leading cause of morbidity and mortality in low and middle-income countries. Substance use negatively affects TB treatment outcomes. Our recent study has found that khat use predicted poorer adherence to anti-TB medications. However, there is scarce longitudinal study on predictors of khat use among outpatients with TB, and this study aimed at addressing this research gap. METHODS: From October 2017 to October 2018, 268 outpatients with tuberculosis on DOTs were enrolled in a longitudinal study from 26 health institutions in Southwest Ethiopia. Structured questionnaires translated into local languages (Afaan Oromoo and Amharic) were used to assess khat use. Patients were followed for six months, and data were collected on three occasions during the follow-up. A generalized linear mixed model was used to identify the relation between khat use and predictors. Model fitness was checked using the Bayesian Information Criterion (BIC). Odds ratio (OR) and 95% CI were used to describe the strength of association between the outcome variable and predictors. RESULTS: The overall prevalence of khat use at baseline and first follow up was 39.2% while it was 37.3% at second follow up. Of this, 77.1% and 96.2% of them believed that khat use reduces the side effects of anti-TB medications and symptoms of tuberculosis respectively. In the final model, being male (aOR = 7.0, p-value = 0.001), being government employee (aOR = 0.03, p-value≤0.001) and presence of alcohol use disorders (AUD) (aOR = 2.0, p-value≤0.001) predicted khat use among outpatients with tuberculosis. CONCLUSION: A considerable proportion of patients with TB used khat throughout DOTs and wrongly perceived that it had health benefits. The finding implies that all patients diagnosed with TB should be screened for khat use, and a particular emphasis should be given to males and individuals with a history of alcohol use. Moreover, further studies are needed to assess patients' beliefs regarding the benefits of khat use so that interventions can be developed.

Khat use and intimate partner violence in a refugee population: a qualitative study in Dollo Ado, Ethiopia.

BACKGROUND: Intimate partner violence (IPV) is the most common form of gender-based violence affecting women and girls worldwide and is exacerbated in humanitarian crises. There is evidence that substance use is associated with male perpetration of IPV. Consumption of khat -a plant containing amphetamines traditionally chewed in the horn of Africa and legal in some countries including Ethiopia-may increase risk of IPV toward women. This analysis aimed to assess perceptions on khat use among Somali refugees in Dollo Ado, Ethiopia and its association with IPV to inform an IPV and HIV prevention intervention. METHODS: A descriptive qualitative study comprising individual interviews (n = 30) and focus group discussions (n = 10) was conducted in Bokolmayo refugee camp in Dollo Ado, Ethiopia in October 2016. A purposive sample of male and female Somali refugees, religious and community leaders, and service providers (n = 110 individuals; 44 women and 66 men) was included. Trained interviewers from the camp conducted the interviews and discussion, which were audio recorded, transcribed and translated. A content analysis was conducted on coded excerpts from the transcripts to identify factors contributing to IPV toward women, including khat use. RESULTS: Participants reported that displacement has resulted in limited employment opportunities for men and increased idle time, which has led to increased khat use among men as a coping mechanism. Male khat use was perceived to be associated with perpetration of physical and sexual IPV through several mechanisms including increased anger and aggression and enhanced sexual desire. Khat use also contributes to intra-marital conflict as money allocated for a household is spent on purchasing khat. CONCLUSION: Khat use should be addressed as part of IPV prevention programming in this context. Livelihood interventions and other strategies to improve economic conditions, should be explored in collaboration with refugee camp authorities and community leaders as a potential avenue to mitigate the impact of khat use on women and families.

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.

Synthetic cathinones - From natural plant stimulant to new drug of abuse.

As recreational substances, synthetic cathinones started to be used at the beginning of the 21st century. There is still limited data on these compounds, introduced to the illicit drug market for the most part after 2009. Considering that synthetic cathinones are currently the second largest group of new psychoactive and dangerous substances among over 670 new psychoactive substances identified in Europe and monitored by the EMCDDA, research on them should be regarded as extremely important. This review focuses on the availability of synthetic cathinones on the illicit drug market, presentation of current trends in the use of these substances, and their mechanisms of action and toxicity. The authors discuss cases of intoxication with synthetic cathinones and post-mortem diagnostics as well as the problem of combined used of synthetic cathinones with other psychoactive substances. Literature as well as clinical and forensic data indicate the need for further research on the metabolism, toxicokinetics, toxicodynamics, clinical effects, and addictive potential of synthetic cathinones, especially in the context of potential threats caused by increased consumption of this group of drugs in future.

Khat Chewing Induces a Floral Shift in Dental Material-Associated Microbiota: A Preliminary Study.

BACKGROUND The habit of khat (Catha Edulis Forskal) chewing is widely practiced in the southern regions of Saudi Arabia, Yemen, and East Africa. This social habit has tremendous effects on oral and general health of khat chewers. Khat may affect bacterial species in plaque biofilms on oral rehabilitation materials. This preliminary case-controlled study aimed to assess and compare the effect of khat chewing on bacterial biodiversity between non-khat chewers (NKC) and khat chewers (KC) in oral biofilms on oral rehabilitation materials using polymerase chain reaction (PCR). MATERIAL AND METHODS Fifty participants were organized into 2 equal groups of NKC and KC, each containing 5 subgroups related to filling material type. Some participants had amalgam (A) or composite (C) restorations, while others had feldspathic porcelain (FP), nickel chromium (NC), and zirconia ceramic (ZC) crowns or bridges. Oral biofilm samples were collected from all participants, DNA was extracted, and samples were subjected to PCR. Bacterial species were then identified and counted. PCR products were sequenced to detect similarity. Partial 16S rRNA gene sequences of the current study samples were compared with 16S rRNA gene sequences from GenBank using BLAST on the National Center for Biotechnology Information website. RESULTS The Streptococcus sp. was the most common bacterial species among our participants (40; 80%), followed by Lactobacillus and Veillonella spp., accounting for 12% (6) and 8% (4), respectively. Streptococcus sp. was observed equally among NKC and KC, but Lactobacillus and Veillonella spp. were higher in KC and NKC, respectively. Lactobacillus was associated mainly with prosthetic materials, and Streptococcus was found among all examined dental restorative materials. CONCLUSIONS This research concluded that khat chewing significantly affects bacterial biodiversity in oral biofilms in the presence of different restorative and prosthetic dental materials.

Determination of chiral cathinone in fresh samples of Catha edulis.

The main psychoactive compound in Khat is cathinone which consists of two enantiomers, S-(-)-cathinone being more stimulant than its R antipode. This study aimed to the enantioseparation and determination of these two stereoisomers in different parts of fresh Catha edulis. The samples were solvent extracted and cathinone was derivatized with menthyl chloroformate. The separation of the two diastereomeric derivatives was carried out by gas chromatography and showed an excellent resolution, while their structure was confirmed by mass spectrometry. The quantitative determination of both enantiomers showed a different distribution in various investigated parts of the plant, as shown in their enantiomeric excess. Unlike the results published in some previous articles, the current study confirmed the presence of both S and R cathinone in all parts of the fresh plant. The concentration of S-cathinone was higher in stems while its values were lower in leaves. The obtained concentrations were in the ranges 0.081-0.290 and 0.087-0.211 mg/g for S and R antipodes, respectively. Also, S-cathinone which is the most psychoactive stereoisomer showed an increasing concentration from lower to upper stems of the plant. The present study is the first quantitative investigation of the two cathinone enantiomers in different parts of fresh Catha edulis.

Oral Biofilm on Dental Materials Among Khat Chewers.

BACKGROUND: Nowadays khat chewing habit is increasing among population in southern part of Saudi Arabia, Jazan and till date there is no literature investigating the effect of khat on oral biofilm on dental materials. OBJECTIVE: To evaluate and compare the bacterial biofilm on different types of dental restorative materials used in replacing missing tooth structures among khat chewers and non-khat chewers. MATERIALS AND METHODS: Hundred and twenty biofilm samples were collected from different dental restorations, such as All-ceramic (AL), Metal Ceramic (MC), Metal crowns or bridges (M), Composite (C), Glass Ionomer (GI) and Amalgam (A) restorations in non-khat and khat chewers (K). DNA extraction was done and subjected to PCR. Bacterial species, such as Streptococcus, Neisseria, Bacillus, Granulicatella and Veillonella were identified and counted. PCR products were also sequenced to detect similarity. Association between bacterial type and dental materials among non-khat and khat chewers were tested with Chi-Square test (Fishers Exact test). RESULTS: The frequency and percentage of Streptococcus species were marginally higher among khat chewers (42; 70%) compared with non-khat chewers (38; 63.3%) group. But the Veillonella species were higher among non-khat chewers (9: 15%), compared to the khat chewers group (7; 11.7%). No statistically significant difference was detected among species in both groups. In non-khat and khat chewer group, the maximum hits were related to Streptococcus spp. in glass ionomer, amalgam, and composite (restorative materials), followed by metal ceramic and metal (prosthetic materials). Veillonella spp. showed maximum hits in the metal group among non-khat chewers and in all-ceramic among khat chewers. Statically significant differences were recorded among composite and amalgam samples with p values 0.047 and 0.036 in khat chewer group. CONCLUSION: Khat chewers showed statistically significant differences in oral biofilm in the composite and amalgam restorative materials, but there were no significant differences found among any materials and species between the groups.