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Background: Oral cavity cancers (OCCs) are the sixth most prevalent cancers in the world. There are strong evidences showing the risk of the cigarette smoking, alcohol use, poor oral hygiene and some types of diets in OCCs; however, few studies explored the relationship between opium and its derivatives (O&D) use and OCCs incidence. The aim of this study was to investigate the relationship between consumption of O&D and the incidence of OCCs., Methods: In a case-control; 133 patients with OCCs and 266 healthy controls matched by age, sex, and place of residence were included. Data, including cigarette smoking, O&D, alcohol and others tobacco (Nass, pipe and hookah) use and diet, were collected using a structured questionnaire. The relation between the use of O&D and OCCs was evaluated using conditional logistic regression., Results: Opium ever-use was associated with an increased risk of OCCs (Adjusted Odds Ratio (AOR) =2.36, 95 % CI: 1.16-4.78). A dose-response relation was observed between the amount of daily O&D use and OCCs; and the relation was stronger in high users (AOR for low users = 1.38, 95 %CI: 0.58-3.24 and AOR for high users = 4.85, 95 % CI:1.79-13.11). Those who used opium for more than 18 years were highly at risk of OCCs (AOR= 5.04, 95 % CI, 2.00-12.68). Also, OCCs was higher among subjects starting the use of O&D at younger ages (≤ 50 years old vs never users AOR = 3.32, 95 % CI: 1.19-9.23). The smoking method of consuming O&D increased the odds of getting OCCs more than twice (AOR= 2.02, 95 % CI, 1.03-3.94), and using both smoking and oral consumption simultaneously, increased the odds of getting OCCs more than 8 times (AOR= 8.57, 95 % CI, 1.68-43.70). Also, the use of other tobacco products (Nass, pipe and hookah) increases the odds of getting OCCs by 4 times (AOR= 3.90, 95 % CI, 1.12-13.57) CONCLUSIONS: The results showed that opium use is probably a dose related risk factor for oral cavity cancers. Therefore, it is necessary to implement preventive policies to control the use of opioids., Competing Interests: Declaration of Competing Interest The authors declare that they have no Conflict of interests, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 μg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: The prevalence and burden of substance and opium use have increased worldwide over the past decades. In light of rapid population changes in Tehran, we aimed to evaluate the prevalence of opium and other substance use among adult residents in Tehran, Iran., Method: From March 2016 to March 2019, we utilized data from 8 296 participants in the Tehran Cohort Study recruitment phase (TeCS). We calculated the age-sex-weighted prevalence of substance use and the geographic distribution of substance use in Tehran. We also used logistic regression analysis to determine possible determinants of opium use., Result: We analyzed data from 8 259 eligible participants with complete substance use data and the average age of participants was 53.7 ± 12.75 years. The prevalence of substance use was 5.6% (95% confidence interval [CI]: 4.6- 7.1%). Substance use was more common in males than females (Prevalence: 10.5% [95% CI: 8.6- 12.6%] vs. 0.5% [95% CI: 0.2- 1.2%], respectively). The age-sex weighted prevalence of substance use was 5.4% (95% CI: 4.6-7.1%). Moreover, opium was the most frequently used substance by 95.8% of substance users. Additionally, we found that male gender (Odds ratio [OR]: 12.1, P < 0.001), alcohol intake (OR: 1.3, P = 0.016), and smoking (OR: 8.5, P < 0.001) were independently associated with opium use., Conclusions: We found that the prevalence of substance use in Tehran was 5.6%, and opium was the most frequently used substance. In addition, male gender, lower levels of education, alcohol, and tobacco consumption are the main risk factors for substance use in Tehran. Healthcare providers and policymakers can utilize our results to implement preventive strategies to minimize substance use in Tehran., (© 2024. The Author(s).)

Background/aims: Upper gastrointestinal bleeding (UGIB) is a frequent medical issue. The primary risk factors for bleeding peptic ulcers are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. The association between acute gastric/duodenal ulcer and opium use has been previously proposed; however, there is no available data on endoscopic findings of patients with acute UGIB who use opium., Materials and Methods: In the present descriptive cross-sectional study, endoscopic data of 50 consecutive patients with oral opium use and 50 consecutive patients without any opium use who were admitted for UGIB were recorded. The size (5-10 mm, 11-20 mm, or more than 20 mm), number (single, double, or multiple), and location of the ulcers (esophagus, gastric corpus including the fundus and body, antrum, angulus, or duodenum) were examined by endoscopy in both groups., Results: Three or more ulcers were observed in 46% and 16% of patients with oral opium use and without opium use, respectively (P-value = 0.001). The rate of giant ulcers (> 20 mm) was significantly higher in patients who used oral opium (40% vs. 12%; P-value = 0.007). Esophageal ulcers were also more common in oral opium users (30%) than non-users (8%) with UGIB (P-value = 0.01). Nevertheless, the location of the ulcers between the two groups generally was not statistically different., Conclusions: This study has demonstrated that multiple, large peptic ulcers in GIB are potential complications of oral opium use. This could aid the needed modifications in the treatment protocol for these patients., (© 2024. The Author(s).)

Objective: The scientific literature presents conflicting data on a possible causal relationship between opium users and the development of head and neck cancer (HNC). This study aimed to explore the risk of HNC among opium users is a narcotic addictive drug., Design: A systematic review and meta-analysis encompassed academic databases and gray literature up to May 2023, focusing on epidemiologic observational studies that reported the effect size of the HNC risk and opium use., Results: This study incorporated 14 effect size estimations to examine the association between opium use and the risk of head and neck cancers based on various HNC sub-sites, including the lip and oral cavity, pharynx, and larynx. The random effect model revealed a significant correlation between combined HNCs and opium use (odds ratio [OR]: 4.88; 95 % confidence interval [CI]: 2.99, 7.96). Additionally, opium consumption significantly increased the incidence of lip and oral cavity cancers (OR: 1.82; 95 % CI: 1.25, 2.65). Opium users faced an approximately eightfold increase in laryngeal cancer risk (OR: 7.86; 95 % CI: 4.66, 13.24) compared to non-opium users., Conclusions: In summary, our findings strongly suggest that opium use is emerging as a significant risk factor for HNC. This underscores the need for further research and focused preventive measures to address this concerning association., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC., Methods: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status., Results: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008)., Conclusion: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004-2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4-20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR = 0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR = 0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023.)

Background: We investigated the association between oral candidiasis prevalence and cigarette, tobacco, alcohol, and opium consumption in Rafsanjan, a region in the southeast of Iran., Methods: This cross-sectional study was conducted using the data of Oral Health Branch of Rafsanjan Cohort Study (OHBRCS) as a part of the Rafsanjan Cohort Study (RCS). RCS included in Prospective Epidemiological Research Studies in IrAN (PERSIAN) was begun in 2015 in the Rafsanjan. A full-mouth examination was done by trained dental specialists. Oral candidiasis was diagnosed based on clinical examination. Information about cigarette, tobacco, and opium smoking and alcohol consumption were collected based on data from self-reported questionaries. Univariate and multivariate dichotomous logistics regression were used to assess the association between oral candidiasis and cigarette, tobacco, alcohol, and opium consumption., Results: Among 8682 participants with mean age of 49.94 years, the prevalence of oral candidiasis was 7.94%. There was a direct association between cigarette smoking in current and former cigarette smokers with an increased odds of oral candidiasis (OR: 3.26, 95% CI: 2.46-4.33 and OR: 1.63, 95% CI: 1.18-2.25 respectively) in fully adjusted models. There was a dose-response relationship between the odds of oral candidiasis and dose (OR: 3.31, 95% CI: 2.38-4.60), duration (OR: 2.48, 95% CI: 2.04-3.95) and number (OR: 3.01, 95% CI: 2.02-4.50) of cigarette smoking in the 4th quartile compared to reference group., Conclusions: A dose-response relationship was shown between cigarette smoking and increased odds of oral candidiasis., (© 2023. The Author(s).)

Papaver somniferum L. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of several specific metabolites like BIAs. It has been used as an antitussive and potent analgesic to alleviate mild to extreme pain since ancient times. The extraction of pharmaceutically important alkaloids like morphine and codeine from poppy plant reflects the need for the most suitable and standard methods. Several analytical and extraction techniques have been reported in open literature for morphine, codeine and other important alkaloids which play a vital function in drug development and drug discovery. Many studies suggest that opioids are also responsible for adverse effects or secondary complications like dependence and withdrawal. In recent years, opium consumption and addiction are the most important risk factors. Many evidence-based reviews suggest that opium consumption is directly linked or acts as a risk factor for different cancers. In this review, we highlight significant efforts related to research which have been done over the past 5 decades and the complete information on Papaver somniferum including its phytochemistry, pharmacological actions, biosynthetic pathways and analytical techniques of opium alkaloid extraction and the link between opium consumption and cancer-related updates.

The spreading of opium use poses new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between non-medical opium use and CAD. We set up a case-control analysis, i.e., the Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2004 and 2011. Incident cases with CAD were contrasted with controls for opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4-6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9-31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that non-medical opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Maino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I 2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for 'ever or regular' versus 'never' use of opium ranged from 1.50 (95% CI 1.13-1.99, I 2  = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I 2  = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach., (© 2023. The Author(s).)

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., (© 2022 UICC.)

Limited evidence is available to acknowledge the association between opium use and liver cancer. In a case-control study, we recruited 117 cases of primary liver cancer (PLC) and 234 age and sex-matched neighborhood controls from 2016 to 2018. We calculated odds ratios (OR) for opium use and 95% confidence intervals (95% CI), using conditional logistic regressions. Compared with non-users the adjusted OR (AOR, 95% CI) for opium use was 6.5 (95% CI, 2.87-13.44). Compared with people who had no history of use, a strong dose-response effect of opium use was observed by amount of use (AOR, 10.70; 95% CI, 3.92-28.70). Cumulative use of opium also indicated that using over 30 gr-year could increase the PLC risk dramatically (AOR, 11.0; 95% CI, 3.83-31.58). Those who used opium for more than 21 years were highly at risk of PLC (AOR, 11.66; 95% CI, 4.43-30.67). The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking)., Prevention Relevance: The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely., (©2022 American Association for Cancer Research.)

Background: 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., Methods: 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., Results: 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)., Conclusion: 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., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

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 &lt; 0.05 is considered significant. A total of 170 patients with a mean age of 61.59 ± 9.07 years were finally enrolled in our study. Regarding the severity of vascular involvement, there was a significant difference between the non-opium and opium groups in LAD (P = 0.025), and PLV (P = 0.018) vessels. From the location points of view of obstructive coronary artery involved segments, only in the PDA (P = 0.006), and LCX (P = 0.004) vessels, a significant difference was observed. Moreover, 47.1% of opium and 30.6% of non-opium use group were in the non-low risk SYNTAX score classification which is a statistically significant difference between these two groups (P value = 0.048). Opium, as an independent risk factor for cardiovascular diseases, can have specific effects on angiographic findings in patients with acute coronary syndrome. Likewise, the complexity of CAD in opium users who undergo percutaneous coronary intervention is significantly higher., (© 2022. The Author(s).)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Opium consumption is associated with increased risk of atherosclerosis and a hyper-inflammatory state which are suggested as contributing factors to the development of coronary artery ectasia (CAE). We aimed to determine if opium consumption is an independent risk factor of CAE. This study aimed to explore the relationship between opium consumption and CAE., Methods: In this propensity score-matched study, we enrolled patients who underwent elective coronary angiography between September 2004 and March 2017 in Tehran Heart Center. We studied patients with CAE and without coronary artery disease (CAD) as cases. The control group, patients with normal coronary angiograms, were selected after applying the propensity score matching to match for age, sex, diabetes mellitus, hypertension, hyperlipidemia, family history of coronary artery disease, and cigarette smoking., Results: We studied 242 patients with pure CAE and selected 968 control patients. The prevalence of opium consumption was not significantly different across these groups: 17 (7.5%) in the pure CAE group compared to 76 (8.6%) in the control group (Odds ratio: 0.81; P =0.455). Amongst the patients with pure CAE, Markis scores were not significantly different between opium consumers and non-consumers ( P =0.136)., Conclusion: We found no significant difference regarding opium consumption between patients with pure CAE and those with normal coronary angiograms. In addition, there was no correlation between opium consumption and Markis scores in patients with pure CAE., (© 2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

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., (© 2022. The Author(s).)

Background: The prevalence of opium addiction in Iran is high probably due to the belief that opium has preventive effects against cardiovascular diseases. In the second phase of Kerman coronary artery disease risk factors study, the prevalence, incidence rate, and the association between opium use and other coronary artery disease risk factors (CADRFs) were assessed., Methods: In a cross-sectional study (2014-2018), 9996 inhabitants of Kerman, southeastern Iran, aged 15-80 years were recruited to the study. After taking fasting blood samples, the participants were examined or interviewed for demographic data and CADRFs, including opium use. The participants were categorized into "never", "occasional", and "dependent" users. The association between opium use and CADRFs was assessed with adjusted regression analysis (Stata v.11 software)., Results: The overall prevalence of opium consumption was lower than that of five years earlier (P<0.01). The prevalence was currently higher in men than women and decreased in men between the two phases (P<0.001). There was a positive correlation between opium use and depression (P<0.001), anxiety (P<0.05), and a negative association with the level of physical activity (P<0.001). The five-year incident rate of dependent and occasional opium use was 4.2 and 3.9 persons/100 person-years, respectively. The incidence of opium use was higher in diabetic, hypertensive, depressed, anxious, and obese subjects., Conclusion: The study did not demonstrate any protective effects of opium on CADRFs. Considering the higher rate of opium use in subjects with hypertension, diabetes, obesity, and psychological disorders, the health authorities should implement educational programs to warn and correct the unsafe belief., (Copyright: © Iranian Journal of Medical Sciences.)

Background: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC., Method: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking., Results: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7)., Conclusions: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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., Competing Interests: The authors declare no personal or financial conflicts of interest., (Copyright © 2022 Masoume Mansouri et al.)

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)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Although atherosclerotic cardiovascular disease (ASCVD) and cancer are seemingly different types of disease, they have multiple shared underlying mechanisms and lifestyle-related risk factors like smoking, unhealthy diet, excessive alcohol consumption, and inadequate physical activity. Opium abuse is prevalent in developing countries, especially the Middle East region and many Asian countries. Besides recreational purposes, many people use opium based on a traditional belief that opium consumption may confer protection against heart attack and improve the control of the risk factors of ASCVD such as diabetes mellitus, hypertension, and dyslipidemia. However, scientific reports indicate an increased risk of ASCVD and poor control of ASCVD risk factors among opium abusers compared with nonusers. Moreover, there is accumulating evidence that opium consumption exerts potential carcinogenic effects and increases the risk of developing various types of cancer. We conducted a review of the literature to review the current evidence on the relationship between opium consumption and ASCVD as well as various kinds of cancer. In addition, we will discuss the potential shared pathophysiologic mechanisms underlying the association between opium abuse and both ASCVD and cancer., (2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Cigarettes and opium contain chemicals and particulate matter that may modify the oral microbiota. This study aimed to investigate the association between cigarette and opium use with the oral microbiota. A total of 558 participants were recruited from Iran between 2011 and 2015. Individuals were categorized as never cigarette nor opium users, ever cigarette-only smokers, ever opium-only users, and ever both cigarette and opium users. Participants provided saliva samples for 16S rRNA gene sequencing. Logistic regression, microbiome regression-based kernel association test (MiRKAT), and zero-inflated beta regression models were calculated. For every increase in 10 observed amplicon sequence variants (ASVs), the odds for being a cigarette-only smoker, opium-only user, and both user compared to never users decreased by 9% (odds ratio [OR] = 0.91; 95% confidence interval [95% CI] = 0.86 to 0.97), 13% (OR = 0.87; 95% CI = 0.75 to 1.01), and 12% (OR = 0.88; 95% CI = 0.80 to 0.96), respectively. The microbial communities differed by cigarette and opium use as indicated by MiRKAT models testing the three beta-diversity matrices ( P < 0.05 for all). Three genera were less likely and one genus was more likely to be detected in cigarette-only smokers or opium-only users than in never users. The relative abundance of the phylum Actinobacteria (never, 14.78%; both, 21.20%) was higher and the phyla Bacteroidetes (never, 17.63%; both, 11.62%) and Proteobacteria (never, 9.06%; both, 3.70%) were lower in users of both cigarettes and opium, while the phylum Firmicutes (never, 54.29%; opium, 65.49%) was higher in opium-only users. Cigarette and opium use was associated with lower alpha-diversity, overall oral microbiota community composition, and both the presence and relative abundance of multiple taxa. IMPORTANCE Cigarette smoking and opium use are associated with periodontal disease caused by specific bacteria such as Porphyromonas gingivalis, which suggests a link between cigarette smoking and opium use and the oral microbiota. Alterations of the oral microbiota in cigarette smokers compared to nonsmokers have been reported, but this has not been studied across diverse populations. Additionally, the association of opium use with the oral microbiota has not been investigated to date. We conducted this study to investigate differences in the oral microbiota between ever users of cigarettes only, opium only, and both cigarettes and opium and never users of cigarettes and opium in Iran. Lower alpha-diversity, distinct overall oral microbial communities, and the presence and relative abundance of multiple taxa have been found for users of cigarettes and/or opium.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management., (Copyright © 2021. Published by Elsevier Inc.)

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.

Background: The aim of this study was to investigate the association of denture stomatitis prevalence with cigarette, hookah and opium consumption and also dose-response relationship between the cigarette smoking duration and odds of denture stomatitis in population of Rafsanjan cohort center., Methods: This cross-sectional study based on data of Rafsanjan Cohort Study (RCS) with 10,000 participants. After applying inclusion and exclusion criteria, 1619 participants were included in the analysis. Data were collected by oral examination and completion of pre-designed questionnaires to assess denture hygiene, smoking behavior, opium use and some other exposure variables. Multivariable logistic regression models were fitted to investigate possible association of cigarette, hookah and opium consumption and denture stomatitis., Results: Prevalence of denture stomatitis among all 1619 denture wearers was 21.6%. Cigarette smoking was associated with a higher odds of denture stomatitis, with the adjusted odds ratio (95% CI) of 2.29 (1.53-3.41). Also, dose-response increases were observed with the highest odds ratio in the 4th quartile for denture stomatitis (p-value < 0.001). Opium consumption was associated with a decreased odds of denture stomatitis (adjusted OR; 0.81, 95% CI 0.58-1.13) which was not statistically significant. Also interaction between opium consumption and cigarette smoking was not associated with higher odds of denture stomatitis (adjusted OR: 1.65, 95% CI 0.85-3.22)., Conclusions: Based on the findings of the present study, while cigarette smoking had a dose-response relationship with the increased odds of denture stomatitis; this association was not found with opium consumption., (© 2021. The Author(s).)

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., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most common cancers in the world. Hence, the determination of risk factors of UGI helps to reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study, we examine the causal effect of opium use on the time to UGI cancer death. Based on the Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to the study for four years (2004-2008) and followed annually until July 2018. We used "parametric g-formula" to study the causal effect of opium use on the time to death due to UGI. In this study, the information of 49946 individuals due to missingness were analyzed. So the median of follow-up time was 144 months and the prevalence of opium use was 17% (about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula = 1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results showed a causal effect of opium use on the intensity of upper gastrointestinal cancer death., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: AS is a paid employee of No Way New Way Company. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: A wrong traditional belief persists among people that opium consumption beneficially affects cardiovascular disease and its risk factors. However, no evidence exists regarding the effect of opium consumption or cessation on the long-term risk of major adverse cardio-cerebrovascular events after coronary artery bypass grafting. We therefore aimed to evaluate the effect of persistent opium consumption after surgery on the long-term outcomes of coronary artery bypass grafting., Methods: The study population consisted of 28,691 patients (20,924 men, mean age 60.9 years), who underwent coronary artery bypass grafting between 2007 and 2016 at our centre. The patients were stratified into three groups according to the status of opium consumption: never opium consumers ( n  = 23,619), persistent postoperative opium consumers ( n  = 3636) and enduring postoperative opium withdrawal ( n  = 1436). Study endpoints were 5-year mortality and 5-year major adverse cardio-cerebrovascular events, comprising all-cause mortality, acute coronary syndrome, cerebrovascular accident and revascularisation., Results: After surgery, 3636 patients continued opium consumption, while 1436 patients persistently avoided opium use. The multivariable survival analysis demonstrated that persistent post-coronary artery bypass grafting opium consumption increased 5-year mortality and 5-year major adverse cardio-cerebrovascular events by 28% (hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.06-1.54; P  = 0.009) and 25% (HR 1.25, 95% CI 1.13-1.40; P  < 0.0001), respectively. It also increased the 5-year risk of acute coronary syndrome by 34% (sub-distribution HR 1.34, 95% CI 1.16-1.55; P  < 0.0001)., Conclusions: The present data suggest that persistent post-coronary artery bypass grafting opium consumption may significantly increase mortality, major adverse cardio-cerebrovascular events and acute coronary syndrome in the long term. Future studies are needed to confirm our findings.

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., Competing Interests: Declaration of competing interest All authors have none to declare., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Various types of medications are used as maintenance therapies for substance use disorder; However, the side effects of these drugs are shown to restrict their use and increase the risk of relapse in patients. As a result, alternative maintenance therapies are tested in the hope for optimum therapy. Since opium tincture is a new and innovative maintenance treatment in Iran, we attempted to compare the therapeutic and side effects of opium tincture with two standard therapies, i.e., methadone and buprenorphine. Hence, thyroid function was tested in three methods of maintenance therapies with methadone, buprenorphine, and opium tincture in a cross-sectional study. In this study, 150 patients with the mean age of 51.63 ± 13.56 years and a history of opioid or opioid-derivatives use disorder, underwent the maintenance treatment with methadone, buprenorphine, and opium tincture at Bojnurd Addiction Treatment Centers in northeastern Iran. These patients were selected using convenience sampling. Then, they were placed into three treatment groups of methadone, buprenorphine, and opium tincture. The thyroid functionality was assessed with measuring TSH, fT4, fT3, T3RU, and Anti TPO, carried out in a reference laboratory. Finally, these data were analyzed by ANOVA using SPSS.16 software. The results showed that there was no significant difference in the average levels of TSH, fT3, fT4, and Anti TPO in these treatment groups; except for T3RU concentration, which was increased significantly in the opium tincture group as compared to the methadone treated group. Also, the frequency of fT4, and T3RU disorders demonstrated a significant change in three groups. The findings of the present study demonstrated that opium tincture in comparison with methadone could increase T3RU levels resulting in euthyroidism possibly through TBG.

Background: In recent years, lung cancer (LC) incidence has increased in Iran. The use of opium and its derivatives (O&D) has increased as well. This study aimed to investigate the association between the use of O&D and LC incidence., Methods: In this case-control study conducted in Kerman, Iran; 140 patients with lung cancer and 280 healthy controls matched by age, sex, and place of residence were included. Data, including O&D use, cigarette smoking, alcohol use, and diet, were collected using a structured questionnaire. The relation between the use of O&D and LC was evaluated using conditional logistic regression adjusted for tobacco smoking, education, daily intake of fruit, vegetables, red meat, and hydrogenated fats., Results: Opium ever-use was associated with an increased risk of LC (Adjusted Odds Ratio (AOR) =5.95, 95% CI: 1.87-18.92). Participants were divided into low and high use groups based on the median of opium use in the control group. A significant dose-response relation was observed between the amount of daily O&D use and LC; and the relation was stronger in high users (AOR low users  = 3.81% CI: 1.13-12.77 and OR high users  = 9.36, 95% CI: 2.05-42.72). Also, LC was higher among participants starting the use of O&D at younger ages (≤ 41 years old vs never users AOR = 8.64, 95% CI: 1.90-39.18) compared to those who started at an older age (> 41 years old vs never users, AOR = 4.71, 95% CI: 1.38-16.08). The association between opium, and lung cancer among non-smokers was OR: 6.50 (95% CI: 2.89 to 14.64)., Conclusion: The results of this study show that opium use is probably a dose related risk factor for lung cancer.

Background/aim: Gastrointestinal (GI) cancers are among the most common cancers in the world. Many risk factors may increase the chance of developing GI cancers. In recent years, a number of epidemiological studies have reported evidence of carcinogenic effects of opium in humans. This study aimed to investigate the relationship between opium use and GI cancer., Materials and Methods: This case-control study was performed on 95 patients with GI cancer and 190 healthy individuals (matched for age, sex, place of residence, and smoking) in Rafsanjan, Iran, in 2018. Diet information, as well as history of smoking, the use of hookah, opium, and its derivatives was collected using a checklist in interview sessions. Conditional logistic regression was performed to investigate the proposed relationship and to estimate odds ratios (OR)., Results: After adjusting the confounding variables, the use of opium was significantly associated with an increased risk of GI cancer development (OR = 5.95, 95% CI: 2.4–14.9). Also, a dose-response association was found between the cumulative use of opium and the risk of GI cancers. Consumption of fruit and vegetables reduced the risk of developing GI cancers in opium users (OR = 4.9 and 4.7, respectively)., Conclusion: Opium, in the form used among drug users in this area, can lead to an increased risk of GI cancers. Fruit and vegetables have a protective and modifying effect on the risk of GI cancer development caused by opium consumption., Competing Interests: The authors declare that there is no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

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 O and D, 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 H and N cancers (Adjusted OR: 8.13; CI: 4.08-16.2). A significant dose-response relation between O and D 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.

Opium is considered as the second most abused addictive compound in worldwide. It seems that one of the causes for common consumption of opium in many countries is a traditional belief, even among medical personnel, through which opium might have advantageous influences on cardiovascular events and be beneficial in controlling hypertension, dyslipidemia, and diabetes. According to several investigations, it is thought that opium not only has no beneficial effects on cardiovascular events, but it might have deleterious influences on these settings. As a result, people need to be trained with regard to the adverse effects of opium on cardiovascular events. In this review, we try to go through the understanding of the effects of opium cardiovascular disorders and related complications such as blood pressure, blood sugar, lipid circumstances, and finally atherosclerosis., (© 2018 Wiley Periodicals, Inc.)

Background: Iran is a country with the highest rate of opioid addiction in the world. The most commonly used opioid in Iran is opium, and methadone is in second place. The trend of drug use has changed from opium to methadone from 2006 to 2011. Presence of a large number of addicted people and methadone maintenance therapy clinics make methadone readily available in Iran. Therefore, evaluation of the epidemiological characteristic of methadone toxicity and its effects on the heart is essential., Methods: In This cross-sectional, retrospective, descriptive, analytical study all patients with methadone or opium toxicity who had been admitted to Vasei hospital, Sabzevar, Iran, during the years 2015 and 2016 were included, and their records were evaluated. Demographic data, addiction history, underlying diseases, and the outcome of admission were recorded. Then, corrected QT interval (QTc) of the first ECG of the patients after admission was evaluated., Results: The Majority of toxicities occurred in those above 30 years of age (71.4%), who lived in cities (62.8%), and were married (69.2%). A positive history of addiction was considerably higher in the opium group (72.3% versus 43.3%). There was no significant difference regarding QTc prolongation between patients with methadone and opium toxicity (p = 0.3)., Conclusion: QTc prolongation is one of the adverse effects of methadone or opium overdose. It seems that significant QTc prolongation is not uncommon among patients with opium overdose.

Background: Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium., Objectives: To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal., Search Methods: We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials., Selection Criteria: Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane., Main Results: We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome.Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence)., Authors' Conclusions: Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.

Purpose: Some epidemiological studies have shown an association between opium consumption and the incidence of gastrointestinal (GI) cancer. The present study was designed to investigate the effects of opium on the initiation of GI cancer in rats., Methods: Forty-five rats were randomly divided into three groups; each received different treatment for 40 weeks. The rats in group 1 received purified water, while animals in group 2 were treated with 5 mg/kg diethylnitrosamine (DEN) orally for 8 weeks and continued with purified water by the end of the experiment. The third experimental group received 300 mg/kg opium for 16 weeks and then continued with 50 mg/kg phenobarbital by the end of the 40th week. The growth of tumors in the treated groups was assessed by histological changes and the up/down expression of p53, cdkn1, cdk2, e-cdh, and n-cdh genes in different parts of GI tract., Results: Histological examinations revealed that DEN was able to induce the growth of tumor in GI tract as shown by active mitotic figure in different regions of GI system and hyperplasia of hepatocytes associated with infiltration of inflammatory cells, intestinal villous hypertrophy, and colorectal adenoma. There was also significant (p < 0.05) overexpression of p53, cdk2, and n-Cdh genes in different parts of digestive system in DEN-treated group. However, these pathological changes and the degradation of gene expression were not observed in the opium-treated group., Conclusion: The results of this study suggest that the opium does not promote the initiation of cancer in GI tract.

According to historical evidence, the abuse of opium has been reported all over the globe-specifically throughout Eastern nations-since the sixteenth century. Before that, opium had mostly been applied as medication. Reference has been made in traditional Persian medical literature to the method of cultivation, properties, side effects and toxicity. In sixteenth century Iran, during the reign of the Safavids, opium abuse began. It was from then that prominent Persian scholars started to think of solutions to this societal problem. One of the most famous scholars was Imad al-Din Mahmud ibn Mas'ud Shirazi, who composed a book concerning addiction-Afyunieh, a comprehensive book on the topic of opium and all issues of opium. Furthermore, he recommended methods for reducing opium dose as well as substitution with other medications that had a narrower range of side effects, in order to eradicate dependency upon opium and opium-derived materials. This is most likely the first book that comprehensively addressed opium and discussed drug rehabilitation methodology, in traditional Persian medical literature. In this historical review, the authors have introduced the book Afyunieh, which presents methods for treating addiction to and giving up opium; the text comprises a synthesis of the author's opinions, professional experience and references to the work of other famous physicians., (Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Background: Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data., Methods: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50 045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest., Results: During the follow-up period, 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to non-malignant aetiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose-dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative opium use versus never use (P trend <0.001). The HRs (95% CI) for the associations between opium use and malignant and non-malignant causes of respiratory mortality were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively., Conclusions: Long-term opium use is associated with increased mortality from both malignant and non-malignant respiratory diseases., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis., Methods: The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3., Results: We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05-4.87) and 5.7 (1.9-16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6-7.7)., Conclusion: This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers.