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On the international day to mark awareness of substance abuse, Ahram Online investigates Egypt's growing drug problem. The head of the rehabilitation centre which treated Ahmed confirmed to Ahram Online that Tramadol is the most common drug used by his patients, while heroin, which is much more costly, comes in second. His group of friends in Mahalla all used the popular painkiller, which he claims made it very hard to stop. He describes needing the feeling of 'escape, elation and energy' Tramadol afforded him, which shifted his problem from a psychological addiction to a physical dependency. These include a number of 'macro' factors such as the availability of drugs, the cultural environment which promotes or condones its use, and mainstream culture, in addition to some 'micro' factors such as peer pressure, and more individual factors like curiosity, boredom and seeking escape. It is easily found on Egypt's streets. After the Egyptian revolution, there was a large influx of Tramadol in shipments from China, adds Dr. Consequently people were easily able to access the drug through the black market instead of having to go to a pharmacy with a prescription and get the pills. According to a recent but unpublished report by the National Centre for Criminological and Social Studies, which was conducted across 10 of Egypt's governorates and studied some 25, cases, 50 percent of all psychotropic substance abusers in Egypt use Tramadol, Hegazy explains. The country's most popular drug, which has become increasingly prevalent in the lower-income bracket as it has become more available, is hashish or cannabis. It is so engrained in society that it has become normalised in some parts Egyptian popular culture, including appearing in films. Classification of cannabis in Egypt has varied from it being labelled a 'soft drug' to a 'gateway drug' meaning there is a fear of it leading to dependence on a harder substance such as heroin. AUC academic Amer believes it should not be dealt with lightly. She says it has a highly addictive potential. Egypt is considered a main transit country for the most important drugs in the world, as it lies between the Mediterranean Sea, the Red Sea and the Suez Canal. Additionally, opiates and cannabis are grown in areas in the Sinai Peninsula and Upper Egypt, with most being locally consumed. Cairo, in particular, seems to be a key epicentre of drug abuse. According to a report by the Cairo Medical College in collaboration with the ministry of health, the percentage of drug abuse in Cairo is 7 percent higher than the world average of 5 percent. Abuse is most prevalent in the impoverished districts. The porousness of Egypt's borders and the security vacuum post-revolution has also contributed to the flood of illicit drugs. After the day uprising against former president Mubarak in , she noticed the market open up more, drugs becoming cheaper as dealers laced the original product to sell it quickly to inexperienced users who do not know what it is supposed to taste like. Although there have been no new statistics recorded post-revolution, this figure is expected to have increased, Hegazy concludes. Treating addiction is demanding and complicated, requiring a two-week detoxification period usually in a hospital, in addition to a rehabilitation phase, which takes months, Sherif explains. In Egypt, Sherif adds, a large part of the population knows nothing about treatment options or even where to seek help. Sherif asserts that rehabilitation is an essential part of the treatment because it is important for 'the mind not just the body to be clean', and ensures that the patient is 'ready to face life with its conditions' without resorting to drugs again. Through a number of activities as well as spiritual and psychological treatments, the recovering addicts 'start to understand that happiness does not have to be achieved through the use of drugs. For Ahmed the rehabilitation centre was a lifeline and a place he continues to visit after traumatic events, like the death of his father last month, to counter relapsing. I knew that as soon as I stepped out of this house I would straightaway go and get my fix,' Ahmed says. However, after locking himself up for three days, a friend, also a recovered addict, was able to bring him back to the rehabilitation facility where he could stop the downward spiral. Public hospitals and some treatment centres give help and space for those unable to pay to be supported. While UNODC's Hegazy sees a positive increase in the number of those seeking treatment, AUC assistant professor Amer believes that there are two segments of the population who are often left out: the large bulk of the middle class, and women. He sees this as a product of ignorance in society, associated with not understanding addiction as an illness. In Egyptian culture, if a member of a family is an addict this is seen as direct reflection on the failure of the parents and the child's upbringing. Sherif's centre caters only to male addicts, when he attempted to set up a treatment facility for females only, neighbourhood members objected, claiming it would be associated with a brothel. Youth and teenagers, starting from as young as twelve, are the age group most affected by addiction in Egypt. This huge population creates a significant demand for drugs and attracts most of the cartels in terms of opening new markets and finding new users', asserts UNODC's Hegazy. Tawfiq claimed that in their 'Stop Drugs: Change your life' campaign, a key segment was visiting schools and attempting to talk to students in classes. She describes the negative backlash they faced from the schools they visited, as teachers and heads would either deem it an 'unacceptable' topic to discuss with children, or something that was not even an issue since they claimed only a small part of the population were abusing drugs. On the other hand, one of the major challenges faced by those trying to combat addiction is the normalisation of drugs in society to the extent that characters in movies are filmed casually taking drugs for no particular purpose, as if they were smoking cigarettes, Amer asserts. As drug use becomes more acceptable and consumption and addiction appear to be on the rise, combating the illicit drug trade in Egypt is becoming increasingly important. The drug is part of a web of illicit activities contributing to wider problems in society. A shift in understanding of drug users and abusers is much-needed in an increasingly unstable Egypt. FR AR. Books Home Reviews News. Outcast: Egypt's growing addiction problem. Reuters Photo. This has contributed to its widespread abuse. However, Tramadol is not the only illegal substance plaguing Egypt. Egypt: A main transit spot The geographical positioning of Egypt has contributed to the nation's growing drug issue. Opiates and heroin comes through Egypt from Afghanistan to supply the European market. Short link:. Neymar returns for Al Hilal in Al Ain thriller. White House: Biden 'deeply concerned' about release of documents on Trump tours storm damage, Harris woos moderates as US vote looms. Most Viewed. Rising demand for practical learning. New discoveries at Luxor's Esna Temple uncover Ptolemaic era secrets in Egypt condemns Israeli targeting of Lebanese infrastructure, army. Ahly forward Kahraba omitted, fined ahead of Super Cup final with Zamalek. Also In Features. Charity at a distance: Egyptians rethink Ramadan traditions amid coronavirus restrictions. Memories of Italian Alexandria. Reminiscing about Ramadan TV shows. Ethyl alcohol prices soar in Cairo as supplies disappear from shelves. Egypt in the process of going plastic-free: The little things that make a big difference. Plastics ban in the Red Sea.

Why It Still Sucks To Get High in the Arab World’s Biggest City

Buying Heroin Mansoura

Official websites use. Share sensitive information only on official, secure websites. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. In Egypt, both pregabalin and tramadol misuse increased in the last decade. Although many studies have confirmed the neurotoxic effects of tramadol, those of pregabalin are understudied. The aim of the study is to evaluate the neurotoxic effects of pregabalin compared with tramadol. Thirty male albino rats were included in this experimental study, and they were randomly allocated into three equal groups: group I normal saline , group II tramadol misuse , and group III pregabalin misuse. All rats received the commenced drugs for 1 month. The drug misuse groups showed a significant decrease in weight gain at the end of the study. Open field testing showed the upper hand of controls regarding all of the tested parameters. Tramadol has a more negative impact on the locomotor parameters compared with pregabalin. Both drugs induced relatively low dopamine-1 receptor D1Rs expression to dopamine-2 receptors D2Rs , mimicking the schizophrenia model. Both tramadol and pregabalin were associated with neurotoxic effects in male albino rats. These effects were less noticed with pregabalin. It is suggested that long-term abuse may end in psychosis. Substance misuse is a common serious problem in adolescents, and it eventually leads to crucial psychosocial, medical, and legal problems Rabie et al. Over the previous two decades, the prevalence of this problem has shown a sharp rise in Egypt due to socioeconomic instability Yassa and Badea The prevalence of substance abuse is 0. Tramadol is a centrally acting analgesic with a weak opioid receptor agonistic action. It also inhibits serotonin and norepinephrine reuptake Subedi et al. Since , tramadol misuse has increased admissions to Egyptian addiction treatment facilities Abolmaged et al. This problem motivated the Egyptian health authorities in to move this medication from schedule three to one on the list of highly addictive substances Bassiony et al. Except for controlled pharmaceuticals, one can purchase any drug without a prescription in Egypt and other nations in the Middle Eastern region Wazaify et al. This limitation in tramadol dispensing led to a marked diversion to the misuse of other substances, including pregabalin and certain ophthalmic topical medications e. Off-label uses were for hypnotic-dependent insomnia, alcohol dependence, and withdrawal of benzodiazepines Cairns et al. In the last years, this medication has emerged as an illicit drug with numerous reports of misuse around the world Driot et al. Euphoria and withdrawal symptoms have been reported with its prolonged administration in high doses Carrus and Schifano ; Chiappini and Schifano ; Martinotti et al. There has been a debate regarding the potential abuse of pregabalin in the previous studies. Nonetheless, Althobaiti et al. The previous authors attributed that effect to GLT-1 downregulation Althobaiti et al. From our experience at the Toxicology Unit, Mansoura University Emergency Hospital, many cases presented with an acute overdose of pregabalin who reported a history of regular chronic use of pregabalin. In April , the Egyptian authorities added pregabalin to the controlled medication list Shokry et al. Moreover, the European Union added a warning regarding its misuse to the Summary of Product Characteristics Evoy et al. Currently, there is an evident lack of knowledge regarding the neurotoxic properties of pregabalin. Moreover, there is a clear lack of studies comparing its harmful effect to tramadol. This was a good motive for us to conduct the present study. This work aims to track the dopaminergic receptor expression changes with pregabalin and tramadol misuse. The expected difference the effect size was assumed to be 0. The estimated needed sample size was 21 rats. For more accuracy, the total number increased to 30 rats 10 rats in each group. We included 30 healthy adult male albino rats aged 3 to 6 months — g in the current research. We used the standard laboratory diet and water for feeding. Animals were randomly divided into three groups 10 rats each. In group I control group , each animal received orally 1 ml of normal saline per day by gavage. In group II tramadol misuse group , each animal received a starting dose of 7. In group III pregabalin misuse group , each animal had received a starting dose of As all of the included animals weighed around g range, — g , we preferred to apply this formula for easy drug dosing and doubling for all animals, and that was the same way applied by the previous two relevant pieces of research Badawy et al. At the end of the experiment, we measured the weight of the rats in each study group and compared it with their baseline weight. Male albino rats were subjected to the open field test at the end of the experiment to assess their locomotor activity Huang et al. Chloroform was used to anesthetize the rats before they were sacrificed. The brains were then carefully retrieved and cleaned in normal saline. The right cerebral hemispheres were used within 24 h after sacrificing the rats for RNA extraction. Each reaction was amplified for 40 cycles. Table 1 shows the primer sequences for the genes used in the research. The Ct value of the control gene, glyceraldehyde 3-phosphate dehydrogenase GAPDH , was used to normalize the Ct values for each target gene. For each of the target genes, relative expression was calculated. Periodic acid Schiff PAS stain : to assess glycogenosis and other metabolic abnormalities associated with neurodegeneration Badawy et al. We used ImageJ 1. In the analysis process, three perceptive non-overlapping fields from immunostaining sections from each rat within the three groups were assessed, taking the mean of the three readings to represent each rat. The Kolmogorov—Smirnov test was used to determine the normality of quantitative data. To compare three groups with normally distributed quantitative variables, the one-way analysis of the variance one-way ANOVA was used, and the Kruskal—Wallis test was applied with non-parametric data. For all applied tests, p -values less than 0. Initial body weight was statistically comparable between the three groups. The percent of body weight increase was significantly higher in controls compared to the other two groups Table 2. Open field testing showed the superiority of the control group regarding all of the tested parameters. It was also evident that tramadol negatively affected the open field-testing variables more than the pregabalin effect. The speed, the total distance traveled, and the number of line crossings showed a statistically significant decrease in the tramadol and pregabalin groups compared to the control group. Also, these parameters showed a statistically significant decrease in the tramadol group compared to the pregabalin group. On the other hand, the number of immobile episodes and the time spent in the peripheral zone showed a statistically significant increase in the tramadol and pregabalin groups compared to the control group. Also, these parameters showed a statistically significant increase in the tramadol group compared to the pregabalin group Table 3. The tested four genes showed statistically different expressions among the three groups in the dopaminergic gene expression. However, the expression decreased in association with tramadol group II. On the other hand, dopamine-2 receptors D2Rs and dopamine-4 receptors D4Rs showed a significant increase in both drug misuse groups compared to controls. Both tested pharmaceuticals significantly impacted the dopaminergic gene expression, either by increase or by decrease, according to the receptor type. In all circumstances, the change was much greater in the tramadol group compared to the pregabalin one Table 4. Analysis of the relative expression of dopaminergic receptors gene as measured by real-time PCR of the studied rats within different groups. Still, the granular cells had round cell bodies and a large round open face nucleus. Darkly stained nuclei of neuroglial cells in the intercellular layer were also visible neuropil. The surrounding areas contained glial cells, nerve fibers, and blood vessels Fig. In the tramadol group, the pyramidal cells are shrunken with darkly stained nuclei and surrounded by empty spaces. The granular cells had reduced in size and were surrounded by vacant areas. Apoptotic cells were also seen, which were shrunken and had small, darkly stained nuclei and little acidophilic cytoplasm Fig. Contrarily, the neuropil showed inflammatory cellular infiltrate Fig. There were perineuronal empty spaces and vascular congestion Fig. While in the pregabalin group, some pyramidal and granular cells appeared normal, while others were shrunken with dark nuclei and surrounded by empty spaces. Examination of Congo red-stained sections of the control group revealed dull staining of neurons and neuropil without amyloid deposits Fig. Examination of PAS-stained sections of the control group revealed normal PAS reaction purplish-red , which appeared strong in the pyramidal cells and the granular cells Fig. Immunohistochemical staining of the cerebral cortex of the control group showed negative immunohistochemical staining for p Thus, neurocytes appeared blue Fig. In contrast, in the tramadol group, the cerebral cortex showed more p53 positive cells in the rat cerebral cortex Fig. Immunohistochemical staining of the cerebral cortex of the control group showed that some cells in the cerebral cortex expressed positive nuclear immunostaining for Ki 67 Fig. In the pregabalin group, there were more Ki 67 positive cells compared to the control group. Still, it was less than the tramadol group Fig. Immunohistochemical staining of the cerebral cortex of the control group showed positive GFAP immunostaining in star-shaped glial cells and their processes Fig. Immunohistochemical staining of the cerebral cortex of the tramadol group showed an increase in the percentage of positive GFAP immunostaining in star-shaped glial cells with increased branches of their cytoplasmic processes Fig. In the pregabalin group, the percentage of reaction was more compared to the control group, but less than the percentage of reaction was less than the tramadol group Fig. The number of positive P53 apoptotic cells, the percentage area of positive GFAP immunoreaction, and the percentage area of positive Ki 67 immunoreactions showed a statistically significant increase in the tramadol and pregabalin groups compared to the control group. Also, these parameters showed a statistically significant increase in the tramadol group as compared to the pregabalin group. The tramadol group showed higher positivity for all the tested stains, followed by the pregabalin one, then controls Table 5. Analysis of the number of positive P53 apoptotic cells of the studied rats within different groups. The current research was conducted to study the neurotoxic effects of pregabalin misuse and to compare it with tramadol in rats. To the best of our knowledge, this is the first study comparing the previous two drugs regarding their neurotoxicity. This unique comparison poses an advantageous point in favor of our study. First, one could notice no significant differences between the three study groups regarding their pre-procedural weight, indicating the proper randomization. This should also negate any bias skewing our findings in favor of one group rather than the others. Most clinicians and patients prefer a fixed-dose regimen over a weight-based one, as it is more convenient and easier to prescribe Pan et al. That is the way in the two tested drugs in our investigation, as most doses reported in the literature are adjusted according to day rather than body weight. Also, most papers reporting pregabalin or tramadol administration, whether for therapeutic or addictive purposes, express their doses via the same concept Gajraj ; Lancia et al. One should note that the maximum dose reached was mg per day instead of mg, as we preferred to commence an additional therapeutic dose every 3 days for easy dose calculation Lancia et al. Regarding tramadol, as previously reported, doses up to 6 g per day were used in patients with substance abuse Roussin et al. These neurotoxic effects were induced mostly by the increased doses of the administered drugs. That is the main problem in individuals with substance misuse, who usually have to increase their daily dose to reach the same effect because of drug tolerance. In the tramadol group, we also decided to increase the drug dose in the same manner as the pregabalin misuse group for an easier drug-increase protocol, and the maximum dose commenced was still in the previously reported range when the equivalent human dose was estimated. Our findings showed a significant decrease in the final body weight with tramadol misuse compared to control. That confirms a previous study by Shuey and his coworkers The decrease in weight gain in rats receiving tramadol may be attributed to its gastrointestinal side effects, including loss of appetite Jolobe Generally, when looking at the present findings, a significant decrease in the locomotor activity in the tramadol misuse rats compared to controls can be noticed. That was evident in all subtests of the open field test. This may be explained by the fact that tramadol caused a series of events responsible for neurodegeneration, including inflammation and microglial proliferation mostly in the prefrontal cortex Aktas et al. Our findings showed a significant increase in the time spent in the peripheral zone in the tramadol misuse group. The open field test assesses anxiety and locomotor activity Seibenhener and Wooten Multiple reports have documented the association between drug misuse and anxiety Alves et al. Anxiety, along with the decreased locomotor activity in the drug misuse groups, could explain the decreased tendency of our animals to spend more time in the central zone. Regarding dopaminergic receptors, the current findings showed increased expression of D2Rs and D4Rs associated with tramadol misuse. Conversely, it led to a significant decline in D1Rs and D5Rs expressions compared to controls. According to current research, drug-induced neurotoxicity is caused by the activation of many neurotransmitter systems, including dopamine, which work together to cause brain damage Cadet et al. Dopamine is a neurotransmitter and hormone that is classified as a monoamine catecholamine. It binds to the dopamine receptor and has a variety of actions depending on the receptor type. Dopamine receptors are important in everyday living tasks. The D5Rs appear to perform some of the same functions as D1Rs. Both D1Rs and D5Rs play important roles in conferring the qualities of reward and novelty to information processed by the hippocampus. They modulate hippocampal long-term potentiation and memory in the brain Hansen and Manahan-Vaughan Selective D5R agonists have recently been shown to protect neurons from apoptosis and improve cognitive function Shen et al. Thus, its decline associated with tramadol misuse is a clear and strong mark of increased apoptosis and impaired neurological function. In the same context, the number of apoptotic cells stained positive for P53 increased significantly in the current study. Oxidative stress, genotoxic chemicals, and other conditions cause p53 to accumulate in the nucleus and bind to certain DNA sequences, causing activation of transcription of many apoptosis-related genes Almog and Rotter Chronic opioid treatment in rats has been linked to a significant increase in the pro-apoptotic receptor and intracellular pro-apoptotic components, as previously described Sharifipour et al. In line with the current findings, a prior investigation found that a greater tramadol dose significantly increased p53 gene expression compared to control rats Mohamed and Mahmoud Additionally, Aghajanpour and his colleagues reported that the caspase-3 level, an apoptotic marker, showed a 3. At the same time, tramadol intake in the current study led to a significant rise in GFAP immunoreaction, indicating an increased number of glial cells in the central nervous system CNS. That agrees with Aghajanpour et al. The proposed mechanism is that microglial cells are the main mediators of the neuroinflammatory process in the CNS Liu et al. It is responsible for inflammatory cytokine release leading to neurodegeneration Hoogland et al. On their migration and activation, an inflammatory response is initiated within the prefrontal cortex Dheen et al. In the current investigation, tramadol intake was associated with a significant increase in Ki 67 immunoreaction. That does not mean an underlying proliferation of functioning neurons, as neuronal cells do not regenerate. Thus, the increased proliferation marker applied in the current study reflects the astrogliosis resulting from brain injury. Regarding pregabalin and its effects, the current findings showed a decreased final body weight in the pregabalin misuse rats. Following the current findings, Elgazzar et al. The authors attributed the weight loss to the striking lack of interest in their food intake. Also, Shokry et al. Regarding the open field tested parameters, we noticed a significant decline in all locomotor parameters in the pregabalin group compared to the controls. One could attribute this decline to the sedative effect of pregabalin. Our results could be explained by the reported dose-dependent sedative impact of pregabalin administration in clinical investigations El-Hussiny et al. The inhibitory impact of pregabalin on the release of excitatory neurotransmitters in the brain has been linked to its sedative effect Calandre et al. According to previous neuropharmacological research, pregabalin activates presynaptic voltage-gated calcium channels, with a subsequent decrease of calcium influx into nerve terminals in rats and humans Fink et al. The effect of pregabalin on dopaminergic receptors is understudied in the literature. We noticed that pregabalin induced the same dopaminergic receptor changes as tramadol but with a weaker effect, indicating that pregabalin still has a neurotoxic effect. Still, it is less severe than tramadol. The authors noted a significant increase in positive P53 apoptotic cells in the pregabalin group compared to controls. Previous research reported a significant decline in B-cell lymphoma 2 BCL2 in the pregabalin-dependent group compared to controls. Additionally, they noticed a significant increase in the inducible nitric oxide synthase, a marker of oxidative stress Elgazzar et al. The presence of reactive oxygen species is considered an early marker of cellular apoptosis, as reported by earlier studies Su et al. In the same context, in the study conducted by Sayin and Simsek, administration of a supratherapeutic dose of pregabalin was associated with an increased expression of c-Jun N-terminal kinase JNK , which is a potent initiator of both extrinsic and mitochondrial intrinsic apoptotic pathways Sayin and Simsek Additionally, according to Salem et al. Contrarily, Song et al. Hindmarch et al. The disagreement between the current findings and those researchers is most likely due to differences in pregabalin dosage, duration, and route of administration. The current findings showed a significant increase in the area stained positive for GFAP in the pregabalin group compared to controls, indicating more gliosis. Using a different marker for gliosis nestin , Elgazzar and her associates noted a significant increase in gliosis in pregabalin-dependent animals Elgazzar et al. Of course, the increased Ki 67 expression was secondary to the astrogliosis. When looking at the tramadol and pregabalin effects, it is evident that tramadol was associated with a more neurotoxic effect than pregabalin. However, the difference between the pregabalin group and controls was also significant regarding most of the study variables. Therefore, the neurotoxic effect of pregabalin should be considered, and its prescription should be limited only to indicated cases and under strict supervision. Notably, low D1Rs and relatively high D2Rs expression are well-known markers of schizophrenia Avery and Krichmar Another cornerstone pathology indicator of psychosis is neuroinflammation, which is well marked in the tramadol group compared to the pregabalin group Comer et al. Despite the different mechanisms of action, both drugs induced common psychosis-related mechanisms. These findings may explore a common model for psychosis. The limited sample size included is one of its major limitations. Therefore, this subject should be extensively evaluated in larger-sample studies. Based on the current findings, both tramadol and pregabalin were associated with neurotoxic effects in male albino rats. Further research is required, in animals and humans, to explain the neurotoxic effects of pregabalin abuse in the prefrontal cortex. This work was carried out in collaboration with all authors. All authors read and approved the final manuscript. The research was self-funded by the authors. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. As a library, NLM provides access to scientific literature. Neurotox Res. Find articles by Ahmed E Elsukary. Find articles by Amal A El Bakary. Find articles by Maha E Moustafa. Find articles by Mohammad A El-Kattan. Open in a new tab. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

Buying Heroin Mansoura