Opium-Related Lead Toxicity: An Integrative Review and Case Series.

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.

Spinal anesthesia reduces postoperative delirium in opium dependent patients undergoing coronary artery bypass grafting.

We investigated the effect of high spinal anesthesia on postoperative delirium in opium dependent patients undergoing coronary artery bypass grafting (CABG). The study was conducted in a tertiary referral university hospital on a population of 60 opium dependent patients undergoing CABG surgery. Patients were divided into two groups based on anesthesia protocol. One group were given general anesthesia (GA Group), the other group additionally received intrathecal morphine and bupivacaine (SGA Group). Postoperative delirium (POD) was defined as the main outcome of interest. Incidence of POD was significantly higher in patients of GA Group as compared with those in SGA Group (47% and 17% for GA and SGA respectively; P-value = 0.01). Time to extubation was on average 2.2 h shorter in SGA than in GA (7.1 h and 9.3 h respectively, P-value < 0.001). Intrathecal morphine and bupivacaine reduced the risk of POD after CABG in a population of opium dependent patients.

Opium usage as an etiologic factor of oral cavity cancer.

PURPOSES: The aim of this study was to evaluate the role of opium in causing oral cancer. PATIENTS AND METHODS: Eighty patients and 80 selected matched controls who were referred to the ear-nose-throat department of an academic hospital were included in this study between October 2008 and September 2010. In addition to demographic data, information regarding alcohol, tobacco, and opium use was documented in the subjects. Finally, the effect of each risk factor was assessed. RESULTS: There was no significant difference in patient demographics between the 2 groups. Smoking (P = 0.042) and poor oral hygiene (P = 0.016) significantly correlated with cancer. Finally, opium addiction showed a significant relationship with oral cavity cancer with an odds ratio of 4 (95% confidence interval, 1.2-13.6). CONCLUSION: Opium use is among the possible risk factors for oral cancer.

Opium could be considered an independent risk factor for lung cancer: a case-control study.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and half of all incident lung cancers are believed to occur in the developing countries, including Iran. OBJECTIVE: We investigated the association of opium with the risk of lung cancer in a case-control study. METHODS: We enrolled 242 cases and 484 matched controls in this study. A questionnaire was developed, containing questions on basic demographic characteristics, as well as lifelong history of smoking cigarettes, exposure to passive smoking, opium use and alcohol consumption. For smoking cigarettes and opium and also oral opium intake frequency, duration and cumulative use were categorized into three groups: no use, low use and high use. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Multivariate analysis in men showed that after adjusting for the effect of ethnicity, education and pack years of smoking cigarettes, smoking opium remained as a significant independent risk factor with an OR of 3.1 (95% CI 1.2-8.1). In addition, concomitant heavy smoking of cigarettes and opium dramatically increased the risk of lung cancer to an OR of 35.0 (95% CI 11.4-107.9). CONCLUSION: This study demonstrated that smoking opium is associated with a high risk of lung cancer as an independent risk factor.

Did the Taliban's opium eradication campaign cause a decline in HIV infections in Russia?

We offer a new hypothesis for why HIV infections fell rapidly after 2001 in Russia: the Taliban's opium eradication campaign in Afghanistan reduced the supply of heroin, causing use to fall and, thus, transmission of HIV to fall. We present evidence of the impact of the eradication campaign on the heroin market and show that the fall in HIV infections happened simultaneously in Russia and surrounding countries soon after the eradication campaign. We also show that the decline in HIV infections only occurred in injecting drug users, while other risk groups were unaffected. Limitations to our analysis are discussed.

Effect of opium dependency on secondary intention wound healing in a rat model: an experimental study.

Opium dependency is a social and health problem in some middle eastern countries like Iran. Many of these people may require surgery. This study investigates the effects of opium dependency on histological parameters of secondary intention wound healing in rat. A full-thickness wound (2 × 2 cm in diameters) was created on the dorsum of two groups of rats, a normal control group and a second group of rat depended to opium (Badawy's method). Several times during 14 days postwounding, the wound was excised with peripheral margins of normal skin and was evaluated for cellular population, reepithelialisation and revascularisation. Results are presented as the mean ± standard error. Data were compared by an unpaired t-test or analysis of variance. Histological examination of the wound tissue showed evidence of increased population of fibroblasts, decreased recruitment of neutrophile and plateau of macrophage cells in opium depended animals comparing with control group. In the depended animals, reepithelialisation was seen to be enhanced significantly, while prohibiting progression of revascularisation. This study shows that opium dependency enhances reepitheliazation as well as tissue recruitment of fibroblasts; thereby probable enhancement of secondary intention wound healing.

Opium as a risk factor for early-onset coronary artery disease: Results from the Milano-Iran (MIran) study.

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.

Trends in the Prevalence and Incidence of Opium Abuse and its Association with Coronary Artery Risk Factors in Adult Population in Iran: Findings from Kerman Coronary Artery Disease Risk Factors Study.

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.

Opium consumption and coronary atherosclerosis in diabetic patients: a propensity score-matched study.

There is a traditional belief among Eastern people that opium may have ameliorating effects on cardiovascular risk factors, especially diabetes; thus, it is widely used among diabetic patients. We attempted to investigate the association of opium consumption with coronary artery disease (CAD) in diabetic patients. A cross-sectional study was conducted on diabetic patients undergoing coronary angiography in our center. Out of 1925 diabetic patients included in the study, 228 were opium users, and the remaining 1697 non-opium users were used as a pool of potential comparators. Propensity scores were used to match the 228 opium consumers with 228 matched comparators for age, sex, and smoking status. The Gensini score and extent score were respectively used to assess the angiographic severity and extent of CAD. The mean Gensini score (86.9 ± 62.7 vs. 59.6 ± 43.4, p < 0.0001) and extent score (7.1 ± 2.9 vs. 5.9 ± 2.9, p < 0.0001) were significantly higher in opium user diabetic patients than in non-opium users. After adjustment for potential confounders, a dose-response relationship was observed between dose of opium and the Gensini score ( ß = 0.27, p = 0.04). There were no significant differences between the routes of opium administration (inhalation vs. oral) regarding the severity and extent of CAD. In conclusion, exposure to opium in diabetic patients may be positively associated with the risk of CAD, and with the angiographically determined severity and extent of the disease. Furthermore, dosage of opium consumption may correlate with severity of CAD.

Auditory sensitivity in opiate addicts with and without a history of noise exposure.

Several case reports suggest that some individuals are susceptible to hearing loss from opioids. A combination of noise and opium exposure is possible in either occupational setting such as military service or recreational settings. According to the Drug Enforcement Agency of the U.S. Department of Justice, prescriptions for opiate-based drugs have skyrocketed in the past decade. Since both opium and noise independently can cause hearing loss, it is important to know the prevalence of hearing loss among individuals who are exposed to opium or both opium and noise. The purpose of this research was to evaluate auditory sensitivity in individuals with a history of opium abuse and/or occupational or nonoccupational noise exposure. Twenty-three men who reported opiate abuse served as participants in the study. Four of the individuals reported no history of noise exposure, 12 reported hobby-related noise exposure, 7 reported occupational noise exposure including 2 who also reported hobby-related noise exposure. Fifty percent (2/4) of the individuals without any noise exposure had a hearing loss confirming previous reports that some of the population is vulnerable to the ototoxic effects of opioids. The percentage of population with hearing loss increased with hobby-related (58%) and occupational noise exposure (100%). Mixed MANOVA revealed a significant ear, frequency, and noise exposure interaction. Health professionals need to be aware of the possible ototoxic effects of opioids, since early detection of hearing loss from opium abuse may lead to cessation of abuse and further progression of hearing loss. The possibility that opium abuse may interact with noise exposure in determining auditory thresholds needs to be considered in noise exposed individuals who are addicted to opiates. Possible mechanisms of cochlear damage from opium abuse, possible reasons for individual susceptibility, and recommendations for future studies are presented in the article.

Thomas de Quincey and his restless legs symptoms as depicted in "Confessions of an English Opium-Eater".

Thomas de Quincey, a British writer of 19th century, suffered insomnia from the age of 17 years. In his famous "Confessions of an English-Opium Eater" (1822), he described a symptomatology that could concord with restless legs syndrome long before he became addicted to opium. In this report, we analyze his clinical description and the circumstances leading to his opium addiction.

Opium and heroin alter biochemical parameters of human's serum.

BACKGROUND: Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Long-term consumption of opioids affects homeostasis. OBJECTIVE: To determine the effects of opium and heroin consumption on serum biochemical parameters. METHODS: In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na(+), K(+), Ca(2+), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum. RESULTS: No significant differences were found in Na(+), Ca(2+), BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K(+), and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca(2+) concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels. CONCLUSION: Chronic use of opium and heroin can change serum FBS, K(+), Ca(2+), UA, and cholesterol. SCIENTIFIC SIGNIFICANCE: This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.

Fifty Years of Research and One Conclusion: Opium Causes Cancer.

In September 2020, the International Agency for Research on Cancer (IARC) announced that opium consumption causes cancer in humans - a conclusion drawn after reviewing data from five decades of research. Given the widespread use of opium and its derivatives by millions of people across the world, the classification of opium consumption as a "Group 1" carcinogen has important public health ramifications. In this mini-review, we offer a short history of opium use in humans and briefly review the body of research that led to the classification of opium consumption as carcinogenic. We also discuss possible mechanisms of opium's carcinogenicity and potential avenues for future research.

Effect of persistent opium consumption after surgery on the long-term outcomes of surgical revascularisation.

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.

Effect of opium addiction on new and traditional cardiovascular risk factors: do duration of addiction and route of administration matter?

BACKGROUND: There is a belief among some society that opium has a number of beneficial effects on cardiovascular disease. The aim of the present investigation as a cross-sectional study was to assess this hypothesis. Several biochemical factors (Fasting blood sugar, Cholesterol, Triglyceride, LDL-Cholesterol, HDL-Cholesterol, HbA1C, CRP, Fibrinogen, Factor VII, SGOT, SGPT, Lpa, apo A and apo B were evaluated in opium-addicted men (case) against non opium-addicted men(control). Three hundred and sixty opium-addicted men were divided into three groups according to the route of administration (Orally, Vafour and Sikh-Sang) and each group was divided into four subgroups according to the duration of addiction (5 months, 1 year, 2 years and 5 years). Blood morphine concentration was measured by ELISA method. RESULTS: The results show that morphine concentration was significantly higher in orally administration. In all routes, there was a direct correlation between blood morphine concentration and period of addiction. Regardless to the period and route of administration, the level of HbA1C, CRP, factor VII, Fibrinogen, apo B, Lpa, SGOT, and SGPT were significantly higher in the case subjects as compared with controls and HDL-Cholesterol and apo a were significantly lower in the case subjects. CONCLUSION: This study demonstrated the deleterious effects of opium on some traditional and new cardiovascular disease risk factors. These deleterious effects are related to the period of addiction and their levels are significantly increased after 2 years of addiction. Route of administration impresses cardiovascular risk factors and "Sikh-Sang" showed the worst effect.

Quadriplegia due to lead-contaminated opium--case report.

PURPOSE: Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. CASE REPORT: Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. CONCLUSION: The delayed treatment of lead poisoning may lead to irreversible motor neuron defect.

Opium Withdrawal Delirium: Two Case Reports.

Two patients with opium dependence developed delirium during abstinence. The delirium resolved completely within 48-58 hours of appropriate treatment. Caution needs to be exercised during opioid detoxification in timely detecting and treating potentially life-threatening condition like delirium.