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Purpose: MDMA methylenedioxymethamphetamine is a synthetic compound, which is a structurally derivative of amphetamine. Also, it acts like an amphetamine, structurally, and functionally. It can also inhibit other isoenzymes contributing to its metabolism, including CYP3A4 which is the most important member of the cytochrome P superfamily. Due to the significant potential of abusing tramadol, either alone or in combination with MDMA, the rate of its toxicity and side effects may increase following possible MDMA relevant enzyme inhibition. Afterward, perfusate samples were collected. They were analyzed by HPLC to determine the concentrations of tramadol and its metabolites. These effects usually remain up to hours following ecstasy consumption. Ecstasy is metabolized in the liver by different members of the cytochrome P family. The drug is usually available as a racemic mixture. According to the aforementioned effects of MDMA on CYP2D6 and CYP3A4 isoenzymes, and by considering the roles of these two in tramadol metabolism, and since the consumption rate of MDMA is significant among the youth, evaluating the possible MDMA and tramadol interaction, due to possible simultaneous use of ecstasy and tramadol, to predict the possible related toxicity seems necessary. Serotonin syndrome is one of the important predicted side effects of tramadol and MDMA interaction. Isolated perfused rat liver model is a very common technique, for pharmacokinetic and drug interaction studies. In the mentioned technique, the vascular system and structure of the liver are preserved and isolated from the effects of other tissues and endogenous compounds. Pure powder of ecstasy has been synthesized in the Pharmaceutical Chemistry laboratory, Faculty of Pharmacy, Tehran University of medical sciences. Also, paroxetine was used under the Paxil brand, 20 mg tablets. All chemical materials used in this study, have been provided by the Merck Company Darmstadt, Germany. Millipore Direct-Q system USA was used for obtaining the ultrapure water consumed during the process of the study. Adult male Wistar rats used in the present study weighed between g. They had access to chow and water ad libitum. Animals were divided into three groups, each containing four rats: control, treatment, and positive control. Fifty milligrams of pure ecstasy powder was dissolved in 5 mL of normal saline. Twenty-five milligrams of pure tramadol powder or its metabolites M1, M2, and M5 was dissolved in 25 mL of methanol. The pooled QC concentrations were prepared from the initial stocks by using the Krebs-Henseleit buffer. Paroxetine with a concentration of 0. Then it was dissolved in 20 mL of deionized water. To reach a concentration of 0. The control group was just administered with the same volume of normal saline without ecstasy. Animals were then anaesthetized at day four for liver perfusion. Their portal vein and inferior vena cava were cannulated with intravenous catheters 16—18 gauge. The total volume of the reservoir was mL. They remained stable and constant throughout the study. Perfusate samples were collected at 10 minutes intervals up to 60 minutes, and then 15 min intervals up to minutes. After that, the samples centrifuged and the upper transparent section of the samples were isolated. To determine the concentration of tramadol and its metabolites in perfusate samples, a previously developed high-performance liquid chromatography HPLC was utilized. Excitation and emission wavelengths were read at nm and nm, respectively. The mobile phase was a mixture of water adjusted to pH 2. The whole run time was about 6 minutes, and the retention times of M1, M5, Tramadol, and M2 were 1. The calibration curve and related equation for tramadol and its metabolites were prepared by using the QC concentrations of tramadol and its metabolites. Also, the concentration of the analytes in perfusate samples was determined, at any time, using the equation mentioned before. The area under the concentration AUC versus time curve was calculated by the trapezoidal rule, from zero to time t. The metabolite ratio was equal to the AUC 0-t of each metabolite at the time of t, which was divided by the AUC 0-t of tramadol at the same time. The statistical student t test, with a significance level of 0. Microsoft Office Excel software was also used to draw the graphs. MDMA or ecstasy is one of the synthetic derivatives of amphetamine. It has a similar structure and function to amphetamines. It has been reported that due to the presence of the methylenedioxy group in its structure, ecstasy irreversibly inhibits CYP2D6 mechanism-based inhibition. By considering the possible simultaneous consumption of MDMA and tramadol, and also the involvement of both CYP2D6 and CYP3A4 isoenzymes in tramadol metabolism, it seemed worthwhile to investigate their interaction, focusing on enzymes involved in their metabolism. In addition, several studies considered tramadol as a CYP2D6 probe. To compare the pharmacokinetic parameters, between the control and treatment groups, values of the AUC and the metabolite ratio based on AUC of each metabolite to tramadol AUC were used. However, the metabolite ratio of M1 significantly decreased, following the administration of larger doses of the MDMA. According to the amount of M1 decrease and incomplete M1 production blockage, it can be hypothesized that other important enzymatic reactions also contribute to M1 production which is not inhibited by MDMA. On the contrary, by increasing the dose of ecstasy, M2 production was increased. However, this valueencountered a significant increase after the administration of higher MDMA doses. M2 production is catalyzed by CYP3A4 isoenzyme activity. Three hypotheses may be able to explain the observed phenomenon relating to the increase of M2 production; the metabolism shifts, lack of M2 consumption, and induction of CYP3A4 isoenzyme by the ortho-quinone groups made by MDMA metabolism. Therefore, and in order to compensate for the decrease, a shift in metabolism to M2 production may happen. In the second hypothesis, due to the inhibition of CYP2D6 and its role in the conversion of M2 to M5, the M5 metabolite production pathway was blocked. Thus, the M2 did not consume, and its level remained high. Further investigation was needed in order to accept or reject each of these hypotheses. For this purpose, another control group positive control was added to the present study, where the CYP2D6 was inhibited by paroxetine as a potent, selective CYP2D6 inhibitor. However, the CYP3A4 activity was remained unchanged. Since there was no animal study investigating the paroxetine effects on CYP2D6 in rats, the applied dose in the present study was extracted from human studies. In most studies, 20 mg dose has been given to the patients, daily, weight of 75 kg for three consecutive days. We applied the dose of 0. Compared to the control group, the AUC of tramadol in the paroxetine group did not significantly change. Therefore, the involvement of the other liver isoenzymes in M1 production is proved. Due to the lack of M5 production in all the treatment groups, it can probably be concluded that M5 is mainly produced from O- demethylation of, M2 and its production was blocked by CYP2D6. Full inhibition resulted from MDMA administration. Inhibition of the mentioned pathway would be involved in the elevation of the M2 level. Consequently, it seems that the elevation of M2 production would not be a result of the metabolism shift. According to the high amount of CYP3A4 and its functional role in drug metabolism, at least in common doses of ecstasy, it is not inhibited. On the other hand, the induction of CYP3A4 cannot be completely ruled out. However, it should be considered that many other isoenzymes involved in the metabolism of tramadol and ecstasy, may affect them and result in an increased production of M2. This work was part of a Pharm. D thesis supported by Tehran University of Medical Sciences. Please don't use dangerous characters. Advanced pharmaceutical bulletin. Abstract Purpose: MDMA methylenedioxymethamphetamine is a synthetic compound, which is a structurally derivative of amphetamine. This is an Open Access article distributed under the terms of the Creative Commons Attribution CC BY , which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. Table 1. Read This Article. Article History. Submitted: 30 Dec Google Scholar Profile. PubMed Profile. Share This Article! Export Citation. Cited By. Article Access Statistics.

Substance Abuse among Iranian High School Students

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Official websites use. Share sensitive information only on official, secure websites. To provide prevention programs and educate drug users DUs , the estimation of their population is necessary. This cross-sectional study was performed in summer on people selected through a multistage sampling method based on 14 region of the municipality of Isfahan. The data collection tool was a questionnaire that was previously used in Dr. Banshi's national plan without any changes. The Cronbach's alpha value of the questionnaire was 0. Using correction factors such as transparency of response and the ratio of social network size used in previous national studies, the number of people with high-risk behaviors was estimated. The results were analyzed through NSUM based on survey analysis. Among all kinds of DUs, men were the largest consumers. In both sexes, the prevalence of using opium and its nectar and illegal treatment with methadone and buprenorphine was higher in people of over 30 years of age, while the prevalence of consuming cannabis, ecstasy, tramadol, tobacco products, and stimulants was higher in the age group of 18 to 30 years. The results indicated that the prevalence of different DUs in Isfahan city, especially among men was higher than the reported average especially in young men of years of age. Since the prevalence of drug use varies based on the type of substance used among age groups, targeted preventive planning based on the type of drug used and age group is recommended. To estimate the population size of hidden groups such as drug users DUs is a challenge for researchers and health care practitioners as well as society. The amount and type of drug use differ throughout the world. In a review in , the prevalence of drug injection was estimated to be 0. Despite frequent efforts, for many reasons such as legal prohibition, stigma and discrimination, and lack of social acceptance in many countries of the world including Iran, these groups remain hidden and inaccessible, which makes it difficult to estimate their population size. There are 2 methods for estimating the population size of hidden groups, direct and indirect. Then, considering the social network size in the general population and some other indicators, the size of the hidden population is estimated. This method was used for the first time in to estimate the population size of people lost in the Mexican earthquake. The results of this study can be helpful to provincial policymakers and experts in estimating the extent, direction, and type of preventive activities required, the costs, and required manpower as well as to obtain economic and executive support. The sample size was estimated at about people considering the drug use prevalence of 0. Sampling was performed using non-random multistage sampling; 14 districts of Isfahan municipality were considered as stratified and, based on information obtained from the Health Deputy of Isfahan University of Medical Sciences, the sample size was determined proportionate to the size of each of these districts. Then, a list of crowded areas of the city as clusters was prepared and two clusters were randomly selected from within each district cluster. Within the clusters in the regular days of the week and at busy hours and , a passer-by was randomly selected once every 15 minutes. The study inclusion criteria included residing in Isfahan for at least 2 years, being 18 years of age and older, and having the mental ability to answer the questions. The exclusion criteria included completion of the questionnaire in the previous days and not willing to participate in the study. A standard questionnaire was used for data collection; its validity was evaluated by the experts in the Ministry of Health's Mental Health Bureau and its Cronbach's alpha was 0. Its reliability was evaluated in a pilot study and the kappa coefficient was estimated at 0. Each question is divided into 2 parts based on gender, male and female, and has three age groups: under 18, 18 to 30, and over In each section, if the respondents knew someone, they would report the number of people. The last part included demographic questions i. Four interviewers 2 women and 2 men were selected and trained through a roleplaying method Mr. Tavasoli, Mr. Torkan, Ms. Rezaei, and Ms. Talebi Por. The interviewers were assigned to different districts according to the timetable and based on the age-sex sampling table; they selected the passers-by and asked them for an informed consent. Ethical considerations: All questionnaires were completed anonymously and all information remained confidential. In order to persuade people to answer the questions, the interviewers tried to find a relatively secluded place. Due to the possibility of increasing unwillingness to take part in the study, verbal consent was obtained rather than a written one. In this study, the transparency coefficient varied from 0. The indicators of mean, standard deviation, frequency, and frequency percentage were used to data analysis and independent t-test and chi-squared test were used for data analysis. Thus, participants from each of the 14 regions were weighted based on the population of that area probability weight. The selected clusters from each area were also coded 1 to 4 as primary sampling units. The sex variable was considered as a stratum. A Finite population correlation was used to determine the odds equivalent in selecting the samples. The age of the participants ranged from 18 to 73 years. The mean age SD of the participants was In both genders, most of the participants had a diploma. Most of the participants were married. In all types of drugs, the prevalence of drug use was higher in men than women. Among men, cannabis was the third most used drug after tobacco, and opium and its nectar, while it was the second most used drug among women. In both sexes, the prevalence of opium and Shireh use and illegal treatment with methadone and buprenorphine among people over 30 years of age was higher than that in other age groups. Likewise, the prevalence of cannabis, ecstasy, hallucinogens, tramadol, tobacco, stimulants, and zolpidem among men of years of age was higher than that among the older and younger age groups. In addition, the prevalence of cannabis, stimulants, ecstasy, tramadol, zolpidem, and tobacco, legal treatment with methadone and buprenorphine, and injecting drug use was higher in women of 18 to 30 years of age. Furthermore, the prevalence of injecting drug use and legal treatment with methadone and buprenorphine was 0 in women under 18 years of age Table 2. The results indicated a high prevalence of use of different types of drugs in Isfahan. Tobacco use was had the highest prevalence, followed by opium and cannabis in men, and cannabis and opium among women, respectively. The highest prevalence of drug use in Isfahan was related to tobacco. In a study by Meysamie et al. Evidently, easy and low-cost access to different drug compounds and purity rates are other reasons for increase in drug use. The highest prevalence of the use of ecstasy pills in the city of Isfahan, which was first estimated by the NSUM, was in the sexually active age group of years. Prolonged duration of ejaculation may be one of the reasons for the use of ecstasy pills. The present study estimated the prevalence of zolpidem in Isfahan through NSUM for the first time, and the results indicated that the use of this hypnotic drug was much higher than the expected medical consumption, especially in people of 18 to 30 years of age. There have been reports of zolpidem addiction in athletes, physicians, and students, necessitating attention to this modern addiction and examination of the causes of young people's tendency to take this drug. The prevalence of injecting drug use in Isfahan was lower than estimations in the studies by Baneshi , 2 and Nikfarjam et al. Female sex workers, homosexual men, and injecting drug users IDUs are the 3 most vulnerable groups of a society at risk of developing HIV. In the present study, it was estimated that more than one-third of men who inject drugs had a constant behavioral addiction, while the prevalence of injecting drugs in women was 0. The results of this study indicated that the prevalence of different drug abuse types among men is more likely than women. According to the results of the present study, the highest prevalence of drug use among men and women was observed in the age groups of 18 to 30 and over 30 years, which is in line with the study by Nikfarjam et al. Evidently, it is also important to pay attention to children of less than 18 years of age. A study by Ranjbaran et al. One of the limitations of the present study was the impossibility of household-based random sampling due to the sensitivity of the considered subject, i. Therefore, through multistage sampling and random selection of people at specified intervals, we attempted to approach the sampling systematically. Second, there is likely reporting bias because some refusing people to participate in the study may recognize many DUs in their social network. However, due to the inability to track people, it was not possible to check and compare the characteristics of DUs with those participating in the study. Third, the size of the social network of DUs is smaller than that of the general population, 7 which will cause underestimation. Moreover, the size of the social network of the general population may vary by gender and age, and even by various regions of the country. However, due to the lack of accurate information in this regard, it was decided to use the indices used in earlier studies in Iran. The results of the present study showed that the prevalence of drug use in Isfahan city, especially in men, is significant and in some cases even higher than the average reported in other studies in the country. Since the prevalence of drug use varies by the type of substance used in the age groups of and over 30 years, targeted preventive planning by type of drug and age group is recommended. The authors would like to thank all those who helped us with this project, including the interviewers. They would also like to thank the Social Deputy of the Police Command of Isfahan who assisted in the performance of our citywide survey, Ayandeh Pazhouhi Center associated with Kerman University of Medical Sciences for providing the questionnaires and scientific advice, and Dr. Marjan Meshkati and Dr. Ramin Radfar for their scientific and practical advice. Collected data, analysis, and wrote the original draft: MAJ; statistics advisor- contributed to analysis: MB; contributed to analysis, review, and editing: MN. As a library, NLM provides access to scientific literature. Addict Health. Find articles by Meysam Abshenas-Jami. Find articles by Mohamadreza Baneshi. Find articles by Maryam Nasirian. Received May 17; Accepted Jul Open in a new tab. Conflicts of Interest The Authors have no conflict of interest. Similar articles. Add to Collections. Create a new collection. 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