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Abstract: Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly used to prepare opium tinctures for people with chronic diarrhea. Morphine and related opioids are powerful but highly addictive analgesics; designing less addictive opioids is an active area of pharmaceutical research that may lead to significant improvements in chronic pain management. Recently, the International Agency for Research on Cancer (IARC) has classified opium consumption as carcinogenic to humans (Group 1) based on sufficient evidence of carcinogenicity in human studies. However, all human studies analyzed by the IARC Working Group included participants who consumed opium that was mixed, adulterated, and/or contaminated with known and probable human carcinogens (e.g., tarry residues of combusted opium, arsenic, lead, and chromium). The working group considered that these carcinogens were part of the complex mixture that opium is, rather than co-exposure or confounders. No evidence of carcinogenicity was available for pure opium in human, animal, or mechanistic studies. To avoid confusion and concern among health professionals and patients using medicinal opium preparations and in scientists involved in the design and development of new opium derivatives, opium should be classified in Group 3 (not classifiable as to its carcinogenicity to humans). The term ‘street opium’ could be used to refer to opium that probably contains human carcinogens not present in pure opium and should remain in Group 1 (carcinogenic to humans).

The association between methylation of MAOA gene promoter and alcohol and nicotine dependence has been demonstrated in women but not in men yet. Antisocial personality disorder (ASPD) and substance use disorders (SUD) are two types of disorders that could highly be influenced by methylation-induced changes in MAOA function. The aim of the current study is to investigate the effect of opioid addiction on methylation of MAOA gene promoter in males. DNA was extracted from the whole blood of all samples (29 opium-addicted individuals undergoing methadone treatment and 28 healthy people) according to the extraction protocol, followed by treating these samples with bisulfite kits. The investigated region including two CpG islands in the promoter region of MAOA gene contained 35 CpG dinucleotides investigated through Sanger sequencing method. The frequency of methylation at two CpG islands of MAOA gene promoter regions was equal to zero among addicted individuals undergoing methadone treatment and healthy peoples. Then, comparing methylation levels among the study group is not applicable. In conclusion, there was no association between opium addiction and methylation of the MAOA promoter regions in opium-addicted male undergoing methadone treatment.

Laboratories are challenged to distinguish whether a positive urine morphine result is due to heroin use or possible poppy seed consumption. Thebaine is an opium alkaloid that has been shown to be present in the urine of individuals who have consumed poppy seeds, as well as those who have used opium. It is not present in heroin. We present a sensitive, specific liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for thebaine. We show that thebaine is detectable after consumption of two different poppy seed-containing products for up to 72 h in urine. We discuss limitations of the assay and suggest how the test might best be used.

This study was performed to investigate lead levels in neonates born to the mothers suffering from opiate use disorder (OUD) and the association of lead levels with the Apgar score.The present cross-sectional study included 56 neonates who were referred to the neonatal ward of Amir-Al Momenin Hospital, Zabol. The neonates were divided into two groups: the neonates whose mothers suffered OUD and the control group. Data were collected using a researcher-prepared questionnaire, and blood lead level was determined using the atomic absorption method. Data were statistically analyzed.In all, 56 neonates (28 from OUD mothers and 28 from the control mothers) were included in this study. Among the women with OUD, 16 (57%) used inhaled opium, while 12 (43%) consumed opium orally. There was a significant difference regarding Apgar score (9.76 ± 2.11 versus. 7.11 ± 4.21; p = 0.02) and the neonate's blood lead level (2.33 ± 1.3 µg/dl versus 7.33 ± 5.9 µg/dl) between the control and OUD groups (p 0.001). The odds ratio of abnormally elevated blood lead level rose with increasing duration of maternal opiate disorder for opiate usage durations of 3 to 5 years (adjusted odds ratio [OR] 42.82, 95% confidence interval [CI] 3.27-561, p = 0.004) and 5 years (adjusted OR 45.5, 95% CI 2.97-698, p = 0.006).The results of this study suggested a significant relationship between maternal opium consumption during pregnancy and neonatal serum lead levels, as well as decreased neonatal Apgar score.

Objectives Opium use, cigarette smoking, and alcohol consumption are serious health problems in many countries including Iran. The present study aimed to examine the association between the opium use, cigarette smoking and alcohol consumption with liver enzyme levels in Southern Iran. This analytical cross-sectional study was conducted in 2020. The entire population of the Fasa Persian cohort study in the southern region of Iran was selected as the sample. Accordingly, 10,145 people participated in the study. Results Results indicated that there was a significant relationship between cigarette smoking and alcohol consumption with liver enzymes (AST, ALT, and ALP). There was also a significant relationship between inhaled opium and liver enzymes, but oral opium revealed no significant relationship with the activity of liver enzymes. Accordingly, policymakers of the health care system are recommended to hold educational programs to improve the health literacy level of the society and take effective preventative strategies in reducing the use of these substances.

In this article I argue that the scarcity of painkillers in the Global South is driven by a central asymmetry in which the health of developed countries is valued over that of the much poorer countries that comprise the rest of the world. To elucidate this point, I argue that by examining the history of various legal institutions and specific events, like the opioid crisis, that have shaped the global production of opium and production in India, one will be able to see the genealogy of the imbalance and inequality that has always affected care. I turn to the state of Kerala to explore instances in which these legal inflections live within the contemporary guidelines for palliative care, and thus constantly affect the supply and delivery of care. This also ties in with the much longer history of opium control for the growth of the global pharmaceutical industry, within which India has been uniquely placed.

Background Bladder cancer disproportionally affects the communities. While it is the ninth most common cancer in the world, in some parts of Iran including Kerman province it is the most common cancer among men. This study aimed to determine potential risk factors of bladder cancer in Kerman province, Iran. Methods During February to July 2020, in this matched hospital-based case-control study, 100 patients with bladder cancer and 200 healthy individuals (matched in age and sex) were recruited. Socio-demographics status, occupational exposures, common diet, history of drug use and family history of cancer, were collected using a structured questionnaire. Bivariable and multivariable logistic regression were applied and crude and adjusted odds ratios (AOR) along with their 95% confidence intervals (95%CI) were calculated. Data were analyzed using Stata version 14 software. Results Opium consumption, cigarette smoking and low level of income were associated with increased chance of bladder cancer. Compared to never use, use of opium up to 18000 Gram -year was associated with increased chance of bladder cancer (AOR: 6; 95% CI =2.3, 15.5). The chance was higher among those who used opium more than 18,000 Gram - year (AOR: 11.3; 95% CI =2.3, 15.5). In comparison with never smokers, the chance of bladder cancer increased among those who smoked up to 20 pack-year cigarette) (AOR: 3.4; 95%CI= 1.3, 8.9) and those who smoke ≥ 20 pack-year (AOR: 15.8; 95% CI= 5.9, 42.4). Conclusions The observed strong dose-response association between opium consumption, cigarette smoking and bladder cancer highlights the need for extension of harm reduction programs especially in regions with high burden of disease.

The current study aimed to evaluate the levels of some toxic and essential elements (Pb, Cd, Cu, Ti, Ni, Cr, Co, Fe, Ca, Hg, Mn, Se, and Zn) in the urine of opium-addicted compared to non-addicted cases. In this study, 126 participants were recruited and their fasting urine samples were collected (63 opium-addicted and 63 non-addicted subjects served as the reference group). ICP-MS was utilized to detect the concentration of trace elements. Results exhibited that the concentration of all elements than Ni, Cu, and Zn was markedly different between the addicted and non-addicted groups. Compared to controls, the Cd, Cr, Co, Hg, Mn, Pb, Se, and Ti levels were higher among opium-addicted cases (p < 0.05) whereas the Fe and Ca concentrations were higher among controls (p < 0.05). Robust regression analysis showed no statistically significant effect of gender on element levels. It revealed that age was associated with the levels of Ni and Cu only and also the route of administration was related to the urinary levels of Co, Cr, Hg, and Mn. In conclusion, results confirmed that it is opium consumption that affects the concentration levels of most elements.

In a population of 1156 men aged ≥ 60 years, opioid drug use was reported by 4.1% (n = 47) of participants. Among opioids, opium was the most prevalent consuming drug (83%). Adjusting for potential confounders, opioid consumption showed a positive association with osteoporosis.Limited evidence suggest a relationship between opioid consumption and osteoporosis. This study aims to investigate the possible association of osteoporosis and drug use among older adult men of Bushehr, Iran.In this study, 1156 men aged ≥ 60 years of Bushehr Elderly Health (BEH) were included. Bone density and trabecular bone score (TBS) were measured using dual-energy X-ray absorptiometry. Total osteoporosis was noted based on osteoporosis at either site of the lumbar spine, femoral neck, and total hip densitometry. Drug use was defined as a self-reported current use of opioid drugs, either regular (daily) use or irregular consumption. Multivariable modified Poisson regression analysis was used for investigating the association of opioids and osteoporosis, reporting the adjusted prevalence ratio (APR) with 95% confidence interval (CI). The association between drug use and TBS was evaluated using a linear regression model.Opioid drug use was reported by 4.1% (n = 47) of participants. Among drug users, opium was the most prevalent consuming drug (83%). In all, 38.3% of drug users and 22.4% of non-users had osteoporosis (p-value = 0.011). Multivariable analysis showed that adjusting by age, education, smoking, alcohol consumption, body mass index, diabetes, and physical activity, a positive and significant association was detected between opioid drug use and the likelihood of osteoporosis (APR: 1.46, 95%CI: 1.02-2.10). Considering the potential confounders, the results also showed a negative association between drug consumption and TBS (β: - 0.027, 95%CI: - 0.053, - 0.001).Opioid drug use has a positive association with osteoporosis in elderly men, independent of other conventional risk factors. Elderly drug users might be at a higher risk for osteoporotic fractures, given the effect of substance use on cognition. So, osteoporosis among drug users would be of importance, especially in countries where opium consumption is prevalent.

Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18/31), C250T (4/31), and C158A (1/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.

Background Fusarium species are saprophytic fungi with a worldwide distribution. These fungi cause various infections among immunocompromised patients; however, they can also involve immunocompetent individuals. Case presentation We report a case of a 41-year-old Iranian woman who presented with ulcerative lesions on her lips 10 months ago. She had a long history of anxiety but had no history of classical risk factors such as trauma, cosmetic lip tattoo, burning in her lips, smoking or use of alcohol and opium. A skin biopsy from the lower lip was performed and sent for microbiological examinations. Hyaline septate hyphae were seen on direct microscopy with potassium hydroxide. The clinical specimen was subcultured on sabouraud dextrose agar with chloramphenicol and prepared for antifungal susceptibility testing and molecular identification. Considering the minimum inhibitory concentrations (MIC) for antifungals, itraconazole (100 mg orally twice a day) was started for her, and after 2 months, the lesions were treated. She followed up for 3 months, and no signs of disease recurrence were observed. Conclusions Selecting an appropriate treatment strategy according to the laboratory assessments is essential in clinical practice and the management of rare infections to prevent related mortality and morbidity of opportunistic fungal infections.

Introduction In response to a high burden of opioid use disorder (OUD), Iran established a network of opioid agonist treatment (OAT) centres beginning in 2002. To increase treatment diversity, particularly for patients who use opium as their drug of choice, opium tincture (OT)-assisted treatment was introduced to the network. This study aimed to explore factors influencing OT-assisted treatment selection for OUD in Tehran, Iran. Methods We conducted 54 in-depth interviews with patients with OUD (n = 33), family members of patients (n = 9) and drug treatment providers (n = 12). Participants were recruited from 12 drug treatment centres across Tehran, between September and November 2019. All interviews were audio-recorded, transcribed and coded in OpenCode 4.02 software and analysed using thematic analysis. Results Study participants more commonly reported individual-level factors as facilitators (e.g. to reduce harms associated with illicit opioid use, achieve recovery through a gradual dose reduction regimen combined with Congress 60 recovery program) and structural level factors (e.g. low adoption by OAT system and lack of familiarity of treatment providers) as barriers for utilisation of OT-assisted treatment regimens. OT was perceived to produce lower levels of physiological dependence than methadone, but the requirement for twice supervised dosing was restrictive. Low familial and community acceptance were also seen as barriers to access. Discussion and Conclusions This research identified a range of perceived benefits for OT-assisted treatment ranging from harm reduction to an intermediate step to achieve recovery. However, several structural-, individual-, familial- and community-level barriers impede its availability and acceptability.

While a large body of literature has shown the health problems of illicit drug use, research is needed on how substance abuse impacts DNA damage and contaminants in blood, especially given Pb-contaminated opium. This pilot study aimed to evaluate the levels of lead (Pb), 8-hydroxy di-guanine (8-oxo-Gua), and malondialdehyde (MDA) in the blood serum of opium addicts and non-addict people. The current study is a case–control study with a cross-sectional design. A sample of 50 opium-addicted and non-addict adults were chosen for this study using convenience and random sampling methods. Participants were divided into two groups: addicts and non-addicts. The atomic absorption spectroscopy method was used to measure the quantity of Pb, and the Enzyme-Linked Immunosorbent Assay (ELISA) method was used to measure the amount of 8-oxo-Gua and MDA. The data were analyzed using an independent t-test. The results show that the amount of Pb in the blood serum of addicted women and men was higher than levels in non-addict men and women, for the study participants (p-value = 0.001). Blood levels were not significantly different between addicts and non-addicts for men or women for 8-oxo-Gua (p-value = 0.647 for women and p-value = 0.785 for men) and MDA (p-value = 0.867 for women and p-value = 0.995 for men). In general, addicts’ blood Pb levels were found to be substantially higher than those of normal non-addict persons in this pilot study. As a result, testing for blood Pb levels in addicts may be informative in instances when symptoms are inconclusive.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

The potential effects of opium consumption on lipid profile remain unquantified. We considered the association between opium use and dyslipidemia. In this cross-sectional study, we used data obtained from the Rafsanjan cohort study, as a part of the prospective epidemiological research studies in IrAN (PERSIAN) with detailed and validated data on opium consumption and selected other exposures. A total of 9932 adults were included in the study. Logistic regression models were used to assess the relationships of opium consumption with the prevalence of dyslipidemia and lipid disorders. In this population, 73.33% had dyslipidemia and the prevalence rates of high TC, high TG, high LDL and low HDL were 54.24%, 47.45%, 34.43% and 11.91% respectively. After adjustment for all confounders, opium users compared with non-users had lower odds ratios (OR) of high TC and high LDL [0.81 (95% confidence interval, CI 0.71–0.92) and 0.80 (95% CI 0.69–0.93) respectively] and greater OR of low HDL [1.30 (95% CI 1.04–1.62)]. Longer duration of opium consumption resulted in lower ORs of high TC, 0.68 (95% CI 0.55–0.84) and high LDL, 0.82 (95% CI 0.67–0.99), and shorter duration of opium consumption resulted in increased odds of low HDL, 1.30 (95% CI 1.02–1.66). High dose of opium consumption was associated with an OR of dyslipidemia of 0.80 (95% CI 0.65–0.97), high TC of 0.80 (95% CI 0.67–0.95), and high LDL of 0.78 (95% CI 0.64–0.96) and low dose of opium consumption, with an OR of low HDL of 1.30 (95% CI 1.02–1.65). In relation to route of consumption, opium smoking was a risk factor for low HDL with an adjusted odds ratio of 1.31 (1.04–1.63). Opium use was associated with selected changes on serum lipid levels, but opium users had higher frequency of cardiovascular disease history.

Background: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study. Methods: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected. Results: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls. Conclusion: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum. publishedVersion

Opioid use disorder (OUD) is diagnosed using the qualitative criteria defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Diagnostic biomarkers for OUD do not currently exist. Our study focused on developing objective biological markers to differentiate chronic opiate users with OUD from chronic opiate users without OUD. Using biospecimens from the Golestan Cohort Study, we compared the metabolomics profiles of high opium users who were diagnosed as OUD positive with high opium users who were diagnosed as OUD negative. High opium use was defined as maximum weekly opium usage greater than or equal to the median usage (2.4 g per week), and OUD was defined as having 2 or more DSM-5 criteria in any 12-month period. Among the 218 high opium users in this study, 80 were diagnosed as OUD negative, while 138 were diagnosed as OUD positive. Seven hundred and twelve peaks differentiated high opium users diagnosed as OUD positive from high opium users diagnosed as OUD negative. Stepwise logistic regression modeling of subject characteristics data together with the 712 differentiating peaks revealed a signature that is 95% predictive of an OUD positive diagnosis, a significant (p

Lead is a poisonous heavy metal with various known side effects. The effect of opium on raising blood lead concentration (BLC) has been investigated with no general agreement. In Iran, the number of lead poisoning cases has raised among the opium-addicted population. This systematic review and meta-analysis aim to combine the results of previous studies with the Iranian population to investigate the effect of opium on BLC. In this systematic review, PubMed/Medline, Web of Sciences, Embase, and Scopus were searched for studies using the Iranian population to compare the BLC of opium-addicted cases and non-addicted controls till January 2020. A random-effects model was used to pool the results. I-square test was used to assess the heterogeneity of the studies. The effect sizes were standardized mean differences (proxied by Hedges'

Opium sale is prohibited in Iran, and sellers mix it with lead to increase the weight. Herein, we describe neuromuscular findings in nine patients who developed lead poisoning due to opium/drug consumption. The mean age of patients was 53 ± 3.5 years and their mean blood lead level was 122.6 ± 20.8 μg/dL. Most of the patients had an acute/subacute course presenting as axonal or demyelinating sensorimotor polyneuropathy, motor neuron disease, and multiple mononeuropathies with favorable response to the chelation therapy. Lead poisoning should be considered in patients with a history of opium use and neuromuscular symptoms.

Background The prevalence of cardiovascular disease (CVD) is rapidly increasing in the world. The present study aimed to assess the prevalence and Predictors factors of CVD based on the data of Kherameh cohort study. Methods The present cross-sectional, analytical study was done based on the data of Kherameh cohort study, as a branch of the Prospective Epidemiological Studies in Iran (PERSIAN). The participants consisted of 10,663 people aged 40–70 years. CVD was defined as suffering from ischemic heart diseases including heart failure, angina, and myocardial infarction. Logistic regression was used to model and predict the factors related to CVD. Additionally, the age-standardized prevalence rate (ASPR) of CVD was determined using the standard Asian population. Results The ASPR of CVD was 10.39% in males (95% CI 10.2–10.6%) and 10.21% in females (95% CI 9.9–10.4%). The prevalence of CVD was higher among the individuals with high blood pressure (58.3%, p p = 0.018), used opium (18.2%, p = 0.039), had high triglyceride levels (31.6%, p = 0.011), were overweight and obese (66.2%, p p p p p Conclusion The prevalence of CVD was found to be relatively higher in Kherameh (southern Iran) compared to other places. Moreover, old age, obesity, taking sleeping pills, hypertension, drug use, and chronic obstructive pulmonary disease had the highest odds ratios of CVD.

Opioid abuse is a serious problem in the society. Since the first months of COVID-19 pandemic, several myths, rumors and misconceptions have been spread about the benefits of opium consumption for COVID-19 outcome. In addition, data are limited on the relationship between opium abuse and COVID-19 mortality amongst hospitalized COVID-19 patients. In this historical cohort study, we assessed the risks of several variables for mortality amongst all hospitalized COVID-19 patients from the beginning of COVID-19 pandemic in South of Iran from March 15th, 2021 to October 14th, 2021. Data was acquired from the Medical Care Monitoring Center (MCMC), affiliated to Shiraz University of Medical Sciences. A total of 64,427 hospitalized COVID-19 patients were included into the analysis. The mortality rate was 10.59% (n = 6756). Of all, 2030 (3.15%) patients-1702 males and 328 females-reported the positive history of opium abuse with a mean age of 57 ± 17.21 years. The results of multivariable risk showed that the positive history of opium abuse had a significant association with mortality (adjusted RR: 1.173; p = 0.007). Other significant predictive risk factors were male gender, elder ages, and comorbidities such as pulmonary diseases, cardiovascular disease, cancer, nephrological diseases, neurological diseases, and diabetes. However, being a health care worker and having thyroid gland diseases were protective factors amongst hospitalized COVID-19 patients (adjusted RR: 0.650 and 0.642; p = 0.040 and .0001, respectively). Opium abuse is a risk factor for mortality amongst hospitalized COVID-19 patients. It is vital to educate societies about the consequences of unauthorized opium consumption.

Background Lead is a hazardous heavy metal, which causes many problems in the human body. Unfortunately, recent reports showed that smugglers and opium sellers add lead to drugs during the production procedure in order to increase its weight and cost. Purpose The aim of this study was development of a rapid and accurate method for measurement of blood lead levels (BLL) in the oral and inhaled opiate abuser people. Methods BLL in samples obtained from the oral and inhaled opium addicted patients referring to Sina Hospital in Tabriz, Iran, during 2017 was compared with healthy control group (N=15). The wet digestion method was used to prepare whole blood and Mercury Droplet Electrode Polarography (MDEP) method was utilized for measurement of the lead content of digested samples. Results Results showed that there were significant differences between the BLL of samples obtained from oral (17.12±74.61 μg/dL, p Conclusion Based on the results of this study it was observed that BLL in opium addicted people needs to be measured as soon as possible. Furthermore, screening of blood lead concentrations in opium-addicted people with a rapid and accurate MDEP method is very necessary and important.

Methadone maintenance treatment might be commonly associated with lying for several causes or manipulating psychiatrists and therapists by a number of patients. Deceptive patients tend to manipulate their psychiatrists for multiple causes. This study aims to improve clinicians’ therapeutic decision-making by identifying the reasons for increasing daily methadone maintenance dosage among deceptive patients. One hundred ninety-six patients undergoing the Methadone Maintenance Treatment (MMT) with no statistically significant difference between the overall Addiction Severity Index (ASI) scores at different doses of methadone (< 60 mg/d and ≥ 60 mg/d) and Ahvaz Reality Distortion Inventory (ARDI) scores > 30, were examined in the current qualitative study with multiple semi-structural interviews about the reasons for increasing daily methadone maintenance dosage. The investigation results revealed that the most common reasons for increasing daily methadone maintenance dosage among deceptive patients were opium craving, patient willingness to feel euphoria, fear of the withdrawal signs, earn money through the sale of surplus methadone, improve the symptoms of physical and psychiatric comorbidity, forgetting painful memories, curiosity, the influence of others, sexual issues, feeling of well-being, and appearance changes. Given these reasons, any increase in daily methadone maintenance dosage is not necessarily accompanied by improvement in the clinical condition of patients. However, clinicians can make the most appropriate therapeutic decision by putting the psychological assessments and clinical interviews into play.

Opioids have the highest rate of illicit drug consumption after cannabis worldwide. Opium, after tobacco, is still the most commonly abused substance in the Middle East. In addition to the ease of availability, one reason for the high consumption of opium in Asian countries might be a traditional belief among Eastern people and even medical staff that opium may have ameliorating effects on cardiovascular diseases (CVDs) as well as diabetes mellitus, hypertension, and dyslipidemia. Over the last decade, many studies have been performed on humans and animals to evaluate the interplay between opium consumption and stable coronary artery disease, acute coronary syndromes, and atherosclerosis. In this review, we conclude that opium consumption should be considered a risk factor for CVDs. Healthy individuals, as well as cardiac and diabetic patients, should be informed and educated about the hazardous effects of opium consumption on cardiovascular and other chronic diseases.

Pain remains a very pervasive problem throughout medicine. Classical pain management is achieved through the use of opiates belonging to the mu opioid receptor (MOR) class, which have significant side effects that hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effects since the isolation of morphine from papaver somniferum, more commonly known as opium by Sertürner in 1804. The natural products salvinorin A, mitragynine, and collybolide represent three nonmorphinan natural product-based targets, which are potent selective agonists of opioid receptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinal chemistry efforts on these templates and their effects on affinity, selectivity, analgesic actions, and a myriad of other opioid-receptor-related behavioral effects.

AimsTens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.Methods and resultsIn the population-based Golestan Cohort Study—50 045 Iranian participants, 40–75 years, 58% women—we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders—i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4–20) years. During 548 940 person-years—median of 11.3 years, >99% success follow-up—3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49–1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.ConclusionLong-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.

The historical practice of brewing poppy tea for its opioid-like effects is reoccurring with modern-day substance users. We present four postmortem cases with toxicology results that serve as case studies for the potential hazards of poppy tea ingestion. There is limited information regarding the risks of this practice due to the variability of the morphine content of the opium exuded from the plant. While internet tea recipes offer guidance, differences in poppy cultivation, washing, and infusing time are some of the reasons why the beverage may contain inconsistent and clinically significant alkaloid concentrations for each preparation. Variability in opioid tolerance along with additional drugs taken will impact the overall degree of toxicity experienced from the opiates in the tea. Advancements in the genetic modification of the poppy plant could greatly alter the ratio of alkaloids seen in biological fluids and will be highly dependent on the source of the poppy product. The blood concentrations of free morphine and free codeine in cases 1–3 where the toxicity from the tea was considered the primary cause of death were 0.94 and 0.11 mg/L, 0.62 and 0.034 mg/L, and 0.16 and 0.010 mg/L, respectively. The urine concentrations of morphine and codeine were 13 and 0.94 mg/L in case 1 and 16 and 1.6 mg/L in case 2, respectively. The opium alkaloids thebaine and laudanosine were identified qualitatively by our routine organic base/neutral drug detection procedure.

BACKGROUND It is reported that opium consumption during pregnancy is associated with adverse pregnancy outcomes and neurodevelopmental defects in infants. BDNF and NGF alterations during pregnancy cause neurobehavioral deficits in the offspring. The aim of this study was to investigate the effect of opium addiction of pregnant women on BDNF and NGF levels in maternal and umbilical cord blood as well as pregnancy outcome. MATERIALS AND METHODS The present research was a cross-sectional study. Thirty-five addicted pregnant women and 35 healthy pregnant women were included in the study. Blood samples were taken immediately after delivery from the maternal vein and umbilical cord. Then, BDNF and NGF concentrations in serum were measured by ELISA kits. The outcomes of pregnancy were determined by a checklist. Descriptive, t test, Mann-Whitney, and Chi-squared test were used to analyze the data. SPSS version 21 software was used for the analyses. A p-value

Background Restrictive regulations and the increased price of opioids have resulted in the addition of impurities to illicit opioids by drug dealers. Among the adulterants, lead salts are optimal agents to make packages heavier. Consequently, lead toxicity has emerged in the opioid-user population. Objectives Our goal was to review the related literature and describe patients with common presentations of opioid-related lead poisoning to provide a basis to prepare optimal management. Methods A narrative review was performed aiming to study opioid lead poisoning. PubMed and Google Scholar databases were explored with two Medical Subject Heading terms, lead poisoning and substance-related disorders to find a broad but relevant spectrum of articles. Then, the reference lists within those articles were checked to upgrade our literature pool on this issue. Results Ultimately, among English-language articles, 16 were case series and case reports of patients with lead intoxication after opioid consumption. Data pertaining to disease characteristics, diagnosis, and treatment protocols were extracted. Conclusions The clinical presentation of opioid lead intoxication can vary from rather asymptomatic to severely debilitating gastrointestinal or neurologic symptoms. The diagnosis is made by checking lead blood levels after obviating other critical diagnoses and should be considered in each drug user in endemic regions of opioid addiction, such as the Middle East. Management protocols are suggested to cover both features of opioid-related complications and lead toxicity.

Background Encephalopathy is an uncommon but serious presentation of lead toxicity. Objective We aimed to determine and follow-up the brain magnetic resonance imaging (MRI) abnormalities in the patients with lead encephalopathy due to ingestion of lead contaminated opium. Methods In a cross-sectional study during lead-contaminated opium outbreak, all lead-poisoned patients with any signs/symptoms of encephalopathy were included. Results Of 19 patients with lead encephalopathy, five died early and other five could not be sent to MRI during their hospitalization period. Mean age was 51 ± 11 years and males were dominant (89%). Median [IQR] blood lead level (BLL) was 101 [81, 108] μg/dL (range; 50 to 200 μg/dL). There was no correlation between MRI findings and signs/symptoms. MRI was normal in six and abnormal in three. Bilateral symmetric involvement of parieto-occipital lobes was observed. Gray matter, gray-white matter junction, and subcortical white matter were also affected. Follow-up MRI was performed in two with abnormal MRI which showed complete and near complete resolution of the abnormalities after cessation of opium use and treatment. Conclusion: There was no correlation between MRI findings and BLL. Complete recovery of brain MRI lesions was detected after cessation of opium use.

Background In Iran, as in many other Asian and Middle Eastern countries, some believe that opium has beneficial effects on cardiovascular system. Dependent patients suppose that opium has positive effects on cardiovascular function and can prevent or improve cardiovascular diseases; however, only few comprehensive studies evaluating such effects have been performed. Objectives In this study, we sought to clarify the effect of opium on cardiovascular problems by incorporating the previous findings and the current information on the issue and to explain the possible mechanisms of this effect. Methods The available human studies published up to October 30, 2019, were searched in different databases. Case-control, cohort, and cross-sectional studies were retrieved. Papers published in English or those with an English abstract were included. The risk of bias for each included study was assessed based on the Newcastle-Ottawa Scale (NOS). We then categorized the effects of opium on cardiovascular problems along with its probable underlying mechanisms of action. Results In this study, most of the published articles suggested the adverse effects of opium on the cardiovascular system, including atherosclerosis, myocardial infarction, arrhythmia, low ejection fraction, and cardiovascular mortality; however, some articles reported the beneficial or impartial effects of opium on the cardiovascular system. In this article, we have categorized all the effects of opium on cardiovascular system; also, the proposed mechanisms of action of opium in each of the above-mentioned disorders are summarized. Conclusion Although the available evidences were incoherent, it was mostly suggested that opium use does not protect against or improve cardiovascular problems.

Background: Head and Neck (H and N) cancers include malignant tumors of the nasal cavity, pharynx, paranasal sinuses, oral cavity, larynx and salivary glands. Opium use might be related to these cancers. The aim of this study was to investigate the relation between Opium and its Derivatives (O and D) use and the incidence of H and N cancers. Methods: In this case-control study conducted in Kerman, 140 patients with HandN cancers and 280 healthy controls (matched for age, gender, and place of residence) were included. Information about their use of OandD, cigarette smoking, alcohol and diet were collected using a structured questionnaire. Conditional logistic regression was used to investigate the relation between variables. Results: The use of opioids was associated with an increased risk of HandN cancers (Adjusted OR: 8.13; CI: 4.08-16.2). A significant dose-response relation between OandD use was observed, with high use Adjusted OR=8.91; 95 CI: 4.03-19.65 and low use Adjusted OR=6.52; 95 CI: 3.18-13.36. This dose-response association was stronger in patients with laryngeal cancer and opioids use, with high use Adjusted OR = 11.17; 95 CI=4.48-28.09 and low use Adjusted OR = 9.46; 95 CI= 3.97-22.52. Conclusion: The results show that opium use can be considered as an important risk factor for H and N cancers. Also in Iran, opium seems to play a more important role than cigarette smoking. © 2020, Asian Pacific Organization for Cancer Prevention.

Opium is one of the most abused substances in the Middle East. The effects of opium use on coronary artery disease (CAD) are a matter of debate. This study aimed to assess the association between opium use and angiographic findings as well as the complexity of CAD in patients with acute coronary syndrome (ACS) diagnosis. In this case–control study, all patients admitted for coronary angiography from 2019 to 2020 were evaluated. After applying the eligibility criteria, they were categorized into two groups opium and non-opium based on their history of opium use. Both groups were matched regarding the demographic features. The prevalence, location, and severity of obstruction of the vessels were compared between the non-opium and opium groups. The SYNTAX score was also calculated and compared between the two groups. The scores ≤ 22 are considered low risk and the higher scores are a non-low risk. P value

Purpose This study aimed to compare the quality of spinal anesthesia between opium-dependent and opium-naive patients. Design A case-control study. Methods Two groups of subjects including opium-dependent and opium-naive patients (30 per group) were enrolled. Spinal anesthesia was performed using 15 mg of bupivacaine. The level of anesthesia was assessed every minute for 10 min and then every 10 min for 180 min. Motor block was recorded at 10, 60, 120, and 180 minutes. The duration of anesthesia was recorded. Findings The mean duration of spinal anesthesia was significantly shorter in opium-dependent patients (101.45 ± 28.670) than in opium-naive patients (126.14 ± 24.206) (P = .003). The mean onset of sensory block was not significantly different between the two groups (4.14 ± 1.62 vs 3.69 ± 1.36, P = .259). Conclusions Substance abuse affects the duration of spinal anesthesia, so it is recommended to use intravenous medications or higher doses of spinal marcaine for these patients.

Tramadol is an opioid pain medication used to treat moderate to severe pain. Tramadol consumers tend to co-abuse some other substances such as opium, cigarettes, alcohol, and cannabis and each of these substances may impair trace elements homeostasis in the body. Therefore, this case-control study aimed to compare the urinary concentration of some essential and toxic elements in tramadol addiction alone and its co-abuse with cigarette and opium in Western Iran. For this purpose, urine samples were collected in two groups of tramadol (n = 72) and control subjects (n = 62) from March to November 2020. The case group was divided into three groups: tramadol alone, tramadol + opium, and tramadol + cigarettes. Moreover, ICP-MS (Agilent 7900) was used to measure trace element concentrations in the urine samples. Based on our results, Fe was the only element markedly higher among controls as compared to tramadol users (p 0.001). Moreover, the concentration levels of As appeared to be the same among both groups, but the levels of other elements including Ca, Cd, Cr, Mn, Cu, Zn, Co, Ni, Se, and Pb were all significantly higher among tramadol users as compared to control group. The rank-based regression analysis illustrated that no contribution of sex and age effect was found by the regression model on the levels of all 12 studied elements. While, smoking was found to affect the levels of Fe (β = 0.163, P = 0.025) and Co (β = 0.411, p 0.001) so that smoking reduced Fe levels but elevated Co concentration levels. Abuse of tramadol along with cigarettes and opium increased the concentration of some heavy metals in urine samples compared to the control group. However, these results showed no significant effect of age, sex, smoking habit, and amount of tramadol usage on the levels of trace elements.

Background. Epidemiological studies have reported inconsistent associations between opium use and cancer risk. We therefore conducted a systematic review and meta-analysis to investigate the relationship between opium use and cancer risk. Methods. We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until February 2021 and references of retrieved relevant articles for observational studies that reported the risk of cancer in relation to opium use. Random-effects models were used to calculate pooled effect sizes (ESs) as well as 95% confidence intervals (CIs) for the association between opium use and cancer risk by considering opium doses and types, duration of consumption, and routes of opium use. Results. In total, 21 observational articles, with a total sample size of 64,412 individuals and 6,658 cases of cancer, were included in this systematic review and meta-analysis. Ever opium users, compared with never opium users, had 3.53 times greater risk of overall cancer (pooled ES: 3.53, 95% CI: 2.60–4.79, P ≤ 0.01). This positive association was also seen for some individual types of cancers except for esophageal and colon cancers. Also, we found that higher opium doses and higher duration of consumption were associated with an increased risk of overall and individual types of cancer. However, the associations between opium doses and the risk of head and neck and larynx cancers were not significant. In terms of the routes of opium use, both opium ingestion and smoking were positively associated with the risk of cancer. Regarding opium types, we found that using teriak, but not shireh, could increase the risk of cancer. Conclusions. Our findings showed that opium use, particularly in the form of teriak, is a risk factor for cancer.

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in CAD patients with and without opium addiction. This case–control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Background . There is lack of comprehensive data on substance use and associated factors among school students in Delhi, India. Methods . We used a cluster sampling method based on sections of classes in schools to conduct this study in two government-run schools in Delhi. All enrolled students from 8th, 9th and 11th grades participated (n = 405). The WHO Student Drug Use questionnaire was administered in a single session for a class section for assessing substance use. Results . The participation rate was 90.6%. The rates of past 12 months' use of tobacco, alcohol, cannabis and inhalants were 22%, 12.1%, 12.1% and 8.6%, respectively, while rates for 'sedatives and tranquillizers' were 4.9%, opium 2.7% and other opioids 1.2%. Lifetime use of heroin was reported by two students and use in the past 12 months by one student. Multiple substance use was high. Higher age was associated with the use of alcohol and cannabis. According to logistic regression model results, use by a family member significantly increased the probability of using tobacco (adjusted odds ratio [AOR] 11.3; 95% confidence interval (CI) 3.4-37.8) and alcohol (AOR 3.75; 95% CI 5.1-1059.3). Similarly, use by peers significantly increased the probability of tobacco (AOR 7.7; 95% CI 2.0-29.8) and cannabis use (AOR 5.7; 95% CI 1.5-21.5). Having poor harm perception significantly increased the chances of inhalant use by students (AOR 5.5; 95% CI 1.5-20.1). Conclusion . The study results bring to attention the prevalent and important problem of substance use among schoolchildren. We recommend that (i) intervention strategies for school settings are important and need to factor in the use of illicit substances (cannabis); (ii) psychosocial intervention by trained school counsellors in school settings is the mainstay for intervention for cannabis and inhalants; and (iii) heroin users should be referred to healthcare facilities for detoxification.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care(®) II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as “

Background: A major episode of lead poisoning caused by lead-adulterated opium occurred in Iran in 2016. Patients were removed from exposure and treated with chelating agents. A subset of those patients was evaluated in this follow-up study to evaluate treatment efficacy in relation to patient outcome. Methods: Between March 2016 and December 2017, thirty-five male cases of lead poisoning due to ingestion of lead-adulterated opium were followed for two years. There are three patient groups: 1) those who abstained from opium use; 2) those who continued to use potentially contaminated opium; and 3) those who abstained from opium and were placed on maintenance therapy. Maintenance therapy included: methadone and opium tincture, offered by the Opioid Maintenance Therapy (OMT) clinics. Amongst the three patient groups Blood Lead Levels (BLL), complete blood count, and kidney and liver function tests were compared. Findings: The results of BLL, hemoglobin, hematocrit, and aspartate aminotransferase were significantly different between the admission time and follow-up. Of the three patient groups, no difference was detected in these measures. Conclusions: Treatment of lead poisoning combined with OMT proved an effective method to prevent recurrent lead poisoning.

"Chasing the dragon" is a term that originated 150 years ago in China after the Opium Wars to refer to the act of heating opium and inhaling its vapor. The phrase has a second meaning, describing the dangerous pursuit of the mythical, ultimate high. However, health systems are using opioids in the pursuit of something likely mythical but similarly elusive - a passive treatment for pain that is rapid, effective, and safe. Regrettably, this worldwide pursuit is treacherous on an immense scale. The opioid crisis is more severe in the US than in any other country. This may be due, in part, to a cultural problem related to pain: Americans have come to expect quick, easy, physician-provided pain relief. We must admit that pharmaceuticals can neither cure injuries nor correct the underlying cause of any chronic musculoskeletal condition. Fortunately, people who regularly exercise have less pain, and guidelines for the management of painful chronic conditions already recommend exercise therapies over passive care. This suggests that self-care approaches emphasizing exercise are the logical, lowest-cost, first-line approach. For patients requiring guidance with exercise, the stepped care approach to pain management commonly taught in medical school curricula should include guided physical rehabilitation early, if not first. This has been shown to be associated with fewer high-cost services and less opioid medication. Keeping people opioid-naïve, when appropriate, might save tens of thousands of American lives annually and many more globally. Attitudes, behaviors, and policies must evolve to shed the culture of first-line pharmaceutical pain management.

While few studies investigated the incidence of stroke in Iran, no Iranian cohort has estimated the standardized-incidence rate and early fatality of first-ever-stroke subtypes along with associated factors.Golestan Cohort Study is a prospective study launched in northeastern Iran in 2004, including 50,045 individuals aged 40-75 at baseline. Age-standardized incidence rate of first-ever-stroke was calculated per 100,000 person-years, according to World Standard Population. The 28-day case fatality was calculated by dividing the number of fatal first-ever-stroke during the first 28 days by total events. Cox proportional hazard models were conducted to assess incidence and fatality risk factors. We used Population Attributable Fractions to estimate the incidence and early fatality proportions reduced by ideal risk factor control.1,135 first-ever-strokes were observed during 8.6 (median) years follow-up. First-ever-stroke standardized incidence rate was estimated 185.2 (95% CI: 173.2-197.2) per 100,000 person-years. The 28-day case fatality was 44.1% (95% CI: 40.4-48.2). Hypertension and pre-stroke physical activity were the strongest risk factors associated with first-ever-stroke incidence (Hazard ratio: 2.83; 2.47-3.23) and 28-day case fatality (Hazard ratio: 0.59; 0.44-0.78), respectively. Remarkably, opium consumption was strongly associated with hemorrhagic stroke incidence (Hazard ratio: 1.52; 1.04-2.23) and ischemic stroke fatality (Hazard ratio: 1.44; 1.01-2.09). Overall, modifiable risk factors contributed to 83% and 61% of first-ever-stroke incidence and early fatality, respectively.Efficient risk factor control can considerably reduce stroke occurrence and fatality in our study. Establishing awareness campaigns and 24-hour stroke units seem necessary for improving the stroke management in this area.

Opium abuse is one of the social hazards in the Middle Eastern countries. Opium consumption attributes to various malignancies. However, the exact molecular mechanism of this correlation still remains unclear. Cancer and inflammation are closely correlated. Interleukin-33 (IL-33) and its receptors, transmembrane ST2 (ST2L) and soluble ST2 (sST2), have been significantly associated with tumorigenicity. The present study aimed to investigate whether IL-33 and sST2 levels serve as cancer biomarkers in opium users.Serum samples were collected from 100 opium users and 100 healthy non-opium users in a nested case-control design. The subjects with over five years of history of opium abuse were enrolled. To assess the incidence of malignancies, the opium users were followed up from 2014 to 2019. Serum levels of IL-33 and sST2 were measured using an ELISA kit. For comparison of IL-33 and sST2 levels between the groups, two-tailed Student's t test and Mann-Whitney U test were utilized, accordingly. Logistic regression analysis was performed to evaluate the influence of confounders on the incidence of cancer.During the five-year follow-up, eight opium users were diagnosed with cancer. Cancer was developed by 9.3 folds in the individuals abusing opium compared to that in the non-opium users (P=0.040, OR=9.3; 95%CI [1.1-79.4]). Serum levels of IL-33 were found to be significantly higher in the opium users than those in the healthy control group (P=0.001). The sST2 levels were significantly lower in the opium users (P=0.001). The opium users with cancer exhibited significantly higher levels of IL-33 and lower levels of sST2 than the cancer-free ones (P=0.001).Decline in sST2 levels and rise in the level of IL-33 are valuable biomarkers in predicting cancers. Regarding the significant alterations in the levels of these biomarkers in the opium users, as well as those in the opium users diagnosed with cancer, IL-33 and sST2 may serve as potential biomarkers in the early prediction of cancer.

Quackery in medicine is as old as medicine itself. In times of crisis, desperate patients often believe extraordinary claims. In the annals of pain-killer quack medicine, elixirs, nostrums and liniments hold a prominent position. NYU College of Dentistry (NYUCD) has a collection of 234 bottles of such medicines dating from the mid-1800s through 1940. This paper is the second in a series of articles featuring "Elixirs of the Past" in which we bring to light five more samples containing opium