Opium, Street Opium, and Cancer Risk.

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).

Blood lead concentration among oral/inhaled opium users: systematic review and meta-analysis.

Lead is a poisonous heavy metal with various known side effects. The effect of opium on raising blood lead concentration (BLC) has been investigated with no general agreement. In Iran, the number of lead poisoning cases has raised among the opium-addicted population. This systematic review and meta-analysis aim to combine the results of previous studies with the Iranian population to investigate the effect of opium on BLC. In this systematic review, PubMed/Medline, Web of Sciences, Embase, and Scopus were searched for studies using the Iranian population to compare the BLC of opium-addicted cases and non-addicted controls till January 2020. A random-effects model was used to pool the results. I-square test was used to assess the heterogeneity of the studies. The effect sizes were standardized mean differences (proxied by Hedges' g) followed by a 95% confidence interval. Of 417 initial articles, 13 studies met the inclusion criteria to be considered in the meta-analysis. The sample size of eligible studies ranged from 40 to 131 (mean 81.83, SD 27.6). All studies were focused on adults with mean age ranged from 33.5 to 65.15 years old (overall mean 49.0, SD 7.66). There were 13 studies included with 18 Hedges' g effect sizes. Using a random effect model, the pooled effect size was gw = 2.48 (95% CI: 1.58-3.39) and statistically significant in favor of opium-addicted participants. Moreover, heterogeneity was 96.6% (I2=96.6, Q(17) = 504.95, p < 0.001). For studies with large Hedges' g effect sizes (> 4) identified as outliers and removed from meta-analysis. The pooled Hedges' g effect size reduced to 1.39 (95% CI: 0.94-1.85), still highly significant in favor of higher levels of lead in the opium-addicted group. The funnel plot appeared symmetrical confirmed by Egger's test (t = 1.87, p = 0.088), indicating no publication bias present.

A Rapid Mercury Droplet Electrode Polarography Method for Determination of Blood Lead Level in Lead Poisoned People.

BACKGROUND: Lead is a hazardous heavy metal, which causes many problems in the human body. Unfortunately, recent reports showed that smugglers and opium sellers add lead to drugs during the production procedure in order to increase its weight and cost. PURPOSE: The aim of this study was development of a rapid and accurate method for measurement of blood lead levels (BLL) in the oral and inhaled opiate abuser people. METHODS: BLL in samples obtained from the oral and inhaled opium addicted patients referring to Sina Hospital in Tabriz, Iran, during 2017 was compared with healthy control group (N=15). The wet digestion method was used to prepare whole blood and Mercury Droplet Electrode Polarography (MDEP) method was utilized for measurement of the lead content of digested samples. RESULTS: Results showed that there were significant differences between the BLL of samples obtained from oral (17.12±74.61 µg/dL, p<0.0003) and inhaled (19.33±2.257 µg/dL, p<0.0001) opium addicted groups in comparison with healthy control group (4.669±0.3367 µg/dL). CONCLUSION: Based on the results of this study it was observed that BLL in opium addicted people needs to be measured as soon as possible. Furthermore, screening of blood lead concentrations in opium-addicted people with a rapid and accurate MDEP method is very necessary and important.

Encephalopathy following ingestion of Lead-contaminated opium; magnetic resonance imaging findings.

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.

DARK Classics in Chemical Neuroscience: Opium, a Historical Perspective.

Opium is the latex from the opium poppy Papaver somniferum L., which humankind has utilized since ancient Mesopotamia all the way to modern times. Opium used to be surrounded in divine mystery or magic-like abilities and was given to cure a wide variety of diseases until its analgesic, antitussive, and antidiarrheal properties were understood, the resulting alkaloids were isolated, and their structure and properties unmasked. Opium went from being sold in any store front in the form of pills or tinctures with no prescription necessary for purchase or smoked in an opium den down the street, to then bringing about consumer advocacy and the right to know what is in a medication. Legislation was created to limit the prescribing and selling of medications to doctors and pharmacists as well as outlawing opium dens and smoking opium. This review focuses primarily on the uses of opium throughout history, the isolation of the principle alkaloids, and their structure elucidation.

Oxidative stress in opium users after using lead-adulterated opium: The role of genetic polymorphism.

Use of lead-adulterated opium has become one of the major sources of lead poisoning in Iran. This study was designed to assess clinical effects and oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The oxidative stress status in 192 opium users with lead poisoning symptoms measured and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and -T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD) rs1800435 polymorphisms were determined using PCR and PCR-RFLP. The relation between the polymorphisms, BLL, and oxidative stress parameters were analysed using multivariate linear regressions. The common symptoms of lead toxicity were gastrointestinal and neurologic complications. Oxidative stress was significantly higher in opium addicts and lipid peroxidation significantly correlated with BLL. There was significant association between ALAD rs1800435 and BLL, and the BLL was significantly lower in the patients with ALAD 1-2 genotype. Use of lead-adulterated opium causes high frequency of lead toxicity symptoms, hematological and biochemical abnormalities, and oxidative stress which are associated with BLL. Route of opioid use and the polymorphism of rs1800435 in ALAD gene are the major determinants of BLL in lead-adulterated opium users.

Gas chromatographic-mass spectrometric characterization of thebaol, an opium constituent, and its structural analogs.

A GC-MS method is described for the characterization of thebaol, a component of opium poppy. The method includes preliminary sample derivatization to TMS, TBDMS, TFA, PFP and HFB substituted products. Fragmentation of resulting derivatives is unique under electron ionization, and proceeds via consecutive loss of two radicals that violate the "even-electron rule". Peaks of [M-2CH3]+. and [M-C4H9-CH3]+. ions show maximum intensities in the spectra of trimethyl- and tert-butyldimethylsilyl-thebaols. Elimination of perfluoroalkyl and methyl radicals from M+. is characteristic for TFA, PFP and HFB thebaols. The same fragmentation peculiarity is characteristic for derivatives prepared from related natural compounds containing vicinal 2-methoxyphenol moieties. The unique fragmentation of trialkylsilyl and perfluoroacyl derivatives of thebaol can be successfully used for thebaol determination within complex mixtures. This is part 4 from the series "Analytical derivatives in mass spectrometry", parts 1, 2 and 3 see [1-3].

Clinical Aspects of Opium Adulterated with Lead in Iran: A Review.

Adulteration of drugs with poisonous substances during production or consumption has caused numerous health problems. Among contaminants that have the potential of producing poisonous effects are the heavy metals lead, arsenic and thallium that make up an important group of toxic substances. The emergence of these new health problems related to opioid abuse has precipitated this MiniReview on the status of the most hazardous and common opioid adulterants. In fact, adulterated opium is a major public health problem and can threaten the health of users. In this study, we searched for information on opium, opiates, lead poisoning, toxicity, intoxication, Iran and heavy metals in the TUMS Digital Library, PubMed, Scopus, EMBASE and Google Scholar bibliographical databases. This MiniReview primarily included articles on lead poisoning, signs and symptoms, and management in opioid-dependent individuals. Exclusion criteria were articles dealing with animal studies, specific paediatric studies, adulterants other than heavy metals and substances other than opioids. Adulterated opium is one of the new sources of exposure to lead and has precipitated an increase in lead-poisoned cases owing to the widespread use of opium. The toxicology of lead and general guidelines on diagnosis and treatment of lead poisoning is briefly reviewed. The symptoms of lead toxicity mimic several diseases often leading to unnecessary diagnostic methods, misdiagnoses and even surgery. Finally, owing to the fact that lead toxicity shows non-specific signs and symptoms, screening for this disease, by taking blood samples and assessing blood lead levels in high-risk people, should be given an utmost priority. It is recommended that screening tests are adopted and applied for any drug-abusing patient with non-specific subacute signs and symptoms like abdominal pain, constipation and anaemia.

Benzylisoquinoline alkaloid biosynthesis in opium poppy.

Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy.

Selective drug trace detection with low-field NMR.

Advances with para-hydrogen induced polarization open up new fields of applications for portable low-field NMR. Here we report the possibility of tracing drugs down to the micromolar regime. We could selectively polarize nicotine quantities similar to those found in one cigarette. Also less than 1 mg of harmine, a drug used for treatment of Parkinson's disease, and morphine extracted from an opium solution were detectable after polarization with para-hydrogen in single-scan (1)H-experiments. Moreover, we demonstrate the possibility to selectively enhance and detect the (1)H-signal of drug molecules with PHIP in proton rich standard solutions that would otherwise mask the (1)H NMR signal of the drug.

Rapid and sensitive determination of morphine in street opium samples by thermal desorption gas chromatography using a microfurnace pyrolyzer.

Thermal desorption of the alkaloids in opium samples at 300 degrees C using a vertical microfurnace pyrolyzer was followed by their on-line gas chromatographic (GC) analysis on a large-bore glass capillary column. This method permitted rapid and sensitive determination of the content of the main alkaloid, morphine, in the small (ca. 100 microg) opium samples with a relative standard deviation within 4% for 5 runs. The observed morphine contents of about 12 to 15 w/w% in the given opium samples were in fairly good agreement with those estimated by a conventional GC-MS method.

Opium revisited: a brief review of its nature, composition, non-medical use and relative risks.

Unlike the pure opioids such as morphine and heroin, opium is a complex and variable mixture of substances reflecting differences in both the starting material and the traditional practices of the regions in which it is produced. Analytical methods have improved greatly in recent years, to the point that the source of a preparation can often be identified by its opioid content and its impurities. Daily amounts used, both by smoking and by mouth, vary widely from less than a gram to 30 g, equivalent to 75-3000 mg of morphine. The effects of opium are essentially those of morphine but unexpected toxicities, such as oesophageal cancer associated with "dross opium" and polyneuropathy due to deliberate addition of arsenic, are problems in some specific regions. Prevalence of use in different areas and countries is governed by the same factors of ease of availability, price and social acceptance that apply to the use of alcohol and other drugs in western countries. The risk of addiction to opium smoking appears to be somewhat less than to parenteral use of heroin, but appreciably greater than to alcohol. Even in countries where its use is traditional, opium smoking carries substantial risks of harm to health and social functioning.